Gold Clusters: from the Dispute on a Gold Chair to the Golden Future of Nanostructures

molecules

Review Gold Clusters: From the Dispute on a Gold Chair to the Golden Future of Nanostructures

Maria Luisa Ganadu 1,* , Francesco Demartin 2 , Angelo Panzanelli 3, Ennio Zangrando 4 , Massimiliano Peana 3 , Serenella Medici 3 and Maria Antonietta Zoroddu 3,*

1 Department of Humanities and Social Sciences, Università degli Studi di Sassari, Via Roma 151, 07100 Sassari, Italy 2 Department of Chemistry, Università degli Studi di Milano, Via Camillo Golgi, 19, 20133 Milan, Italy; [email protected] 3 Department of Chemistry and Pharmacy, Università degli Studi di Sassari, Via Vienna 2, 07100 Sassari, Italy; [email protected] (A.P.); [email protected] (M.P.); [email protected] (S.M.) 4 Department of Chemical and Pharmaceutical Sciences, Università degli Studi di Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy; [email protected] * Correspondence: [email protected] (M.L.G.); [email protected] (M.A.Z.)

Abstract: The present work opens with an acknowledgement to the research activity performed by Luciana Naldini while affiliated at the Università degli Studi di Sassari (Italy), in particular towards gold complexes and clusters, as a tribute to her outstanding figure in a time and a society where being a woman in science was rather difficult, hoping her achievements could be of inspiration to young female chemists in pursuing their careers against the many hurdles they may encounter. Naldini’s findings will be a key to introduce the most recent results in this field, showing how the chemistry of gold compounds has changed throughout the years, to reach levels of complexity Citation: Ganadu, M.L.; Demartin, F.; and elegance that were once unimagined. The study of gold complexes and clusters with various Panzanelli, A.; Zangrando, E.; Peana, phosphine ligands was Naldini’s main field of research because of the potential application of these M.; Medici, S.; Zoroddu, M.A. Gold species in diverse research areas including electronics, catalysis, and medicine. As the conclusion Clusters: From the Dispute on a Gold of a vital period of study, here we report Naldini’s last results on a hexanuclear cationic gold Chair to the Golden Future of 2+ cluster, [(PPh3)6Au6(OH)2] , having a chair conformation, and on the assumption, supported by Nanostructures. Molecules 2021, 26, experimental data, that it comprises two hydroxyl groups. This contribution, within the fascinating 5014. https://doi.org/10.3390/ field of inorganic chemistry, provides the intuition of how a simple electron counting may lead to molecules26165014 predictable species of yet unknown molecular architectures and formulation, nowadays suggesting

Academic Editor: José A. Gascón interesting opportunities to tune the electronic structures of similar and higher nuclearity species thanks to new spectroscopic and analytical approaches and software facilities. After several decades Received: 5 April 2021 since Naldini’s exceptional work, the chemistry of the gold cluster has reached a considerable Accepted: 14 August 2021 degree of complexity, dealing with new, single-atom precise, materials possessing interesting physico- Published: 19 August 2021 chemical properties, such as luminescence, chirality, or paramagnetic behavior. Here we will describe some of the most signiﬁcant contributions. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in Keywords: gold complexes; gold clusters; transition metal complexes; phosphine ligands published maps and institutional afﬁl- iations.

1. Introduction Luciana Naldini (Scheme1) was born in 1925 in Pisa, where she graduated with Copyright: © 2021 by the authors. full marks in general chemistry. Immediately after the end of the war, she moved to the Licensee MDPI, Basel, Switzerland. University of Milan as an assistant of professor U. Sborgi at the Faculty of General and This article is an open access article Inorganic Chemistry, where she remained even when the chair passed to professor L. distributed under the terms and Malatesta. She taught chemistry for the degree courses of biology, medicine, and geology conditions of the Creative Commons until 1980, when she was appointed full professor at the University of Sassari, where Attribution (CC BY) license (https:// she also became Dean of the Faculty of Chemistry and Director of the CNR (Consiglio creativecommons.org/licenses/by/ Nazionale delle Ricerche) Institute for the Application of Advanced Chemical Technologies 4.0/).

Molecules 2021, 26, 5014. https://doi.org/10.3390/molecules26165014 https://www.mdpi.com/journal/molecules Molecules 2021, 26, x FOR PEER REVIEW 2 of 16

Molecules 2021, 26, 5014 2 of 15

delle Ricerche) Institute for the Application of Advanced Chemical Technologies to Agro- biological problems, until 1995, when she passed away following a serious illness. Her toseminal Agrobiological work is problems,testified by until many 1995, scientific when she papers passed supported away following by a sound, a serious critical illness. ap- Herproach seminal to scientific work is data. testified She attended by many national scientific and papers international supported conferences by a sound, as a criticalspeaker approachand was toalso scientific a science data. columnist She attended. She kept national reminding and international that “The Periodic conferences Table as abelongs speaker to andeveryone” was also every a science time columnist. a colleague She made kept remindingher observe that that “The someone Periodic imitated Table belongs her com- to everyone”pounds. every time a colleague made her observe that someone imitated her compounds.

Scheme 1. Luciana Naldini (1960) (left); Laboratory work in Milan (right); Luciana Naldini is in the Scheme 1. Luciana Naldini (1960) (left); Laboratory work in Milan (right); Luciana Naldini is in the forefront of the picture. forefront of the picture.

ThisThis contribution, contribution, in in addition addition to to being being a a tribute tribute to to Luciana Luciana Naldini Naldini as as a a researcher, researcher, wouldwould also also like like toto underlineunderline the difficulty difficulty women women encountered encountered in in reaching reaching leadership leadership po- positionssitions in in all all spheres spheres of of life, life, and science isis notnot anan exception.exception. ThisThis lack lack of of gender gender equality equality conditionsconditions in in a a scientific scientific institution, institution, which which should should be be founded founded on on the the recognition recognition of of one’s one’s merit,merit, competencies, competencies, and and creativity, creativity, regardless regardless of of other other personal personal features features and and orientations, orientations, deeplydeeply clashes clashes with with the the traditional traditional view view of of science. science. Despite Despite this this situation, situation, she she was was ap- ap- pointedpointed Full Full Professor Professor and and Director Director ofof thethe CNRCNR Institute when she moved moved to to the the island island of ofSardinia, Sardinia, where where she she was was well-liked among colleaguescolleagues andand studentsstudents and and developed developed her her independentindependent field field of of work. work. DuringDuring the the early early years years of of research research in in Milan, Milan, Luciana Luciana Naldini Naldini synthesized synthesized a a series series of of goldgold clusters clusters [1 [1,2],2] comprising comprising six six to to eleven eleven gold gold atoms atoms that that could could not not be be explained explained by by the the standardstandard rules rules of of valence valence and and only only a a few few of of these these have have been been structurally structurally characterized. characterized. AmongAmong them, them, the the unique unique Au Au6 compound6 compound exhibits exhibits a a number number of of intriguing intriguing features features with with respectrespect to to relativistic relativistic effects, effects, aurophilicity, aurophilicity, and and Au Au... …AuAu contacts contacts [ 3[3–6].–6]. These These aspects aspects of of goldgold clusters clusters were were relatively relatively new, new, since since the the first first reports reports of of the the relativistic relativistic effects effects studied studied throughthrough Dirac Dirac scattered-wave scattered-wave calculations calculations dated date backd back to theto the second second half half of theof the 1980s 1980s [7–9 [7–], when9], when also thealso relationship the relationship between between aurophilicity aurophilicity and relativistic and relativistic effects started effects to started emerge to inemerge studies in carried studies out carried on (Ph out3PAu) on 6(Phclusters3PAu)6 [ 10clusters,11] similar [10,11] to similar those prepared to those byprepared Naldini. by SuchNaldini. clusters Such were clusters first reportedwere first in reported a thesis workin a thesis dating work back dating to 1994 back [12], to of 1994 which [12], she of waswhich supervisor, she was andsupervisor, gave additional and gave light additional in this field,light butin this they field, also but concluded they also a periodconcluded of livelya period research of lively activity, research carried activity, out in carried collaboration out in collaboration with her esteemed with her coworkers, esteemed starting cowork- fromers, L.starting Malatesta, from recognized L. Malatesta, as therecognized father of goldas the clusters father chemistryof gold clusters [13], together chemistry with [13], F. Cariati,together M. with Manassero, F. Cariati, G. M. Simonetta, Manassero, and G. many Simonetta, others and that many were involvedothers that in were this excitinginvolved explorationin this exciting of the exploration chemistry of of the gold. chemistry Finally, of within gold. Finally, this fascinating within this area, fascinating we report area, a viewwe report on recent a view studies on recent on electron studies count on electron and aurophilic count and interactions aurophilic of interactions which Naldini of which and coworkersNaldini and laid coworkers the first groundwork. laid the first groundwork. 2. Results In her career, Luciana Naldini was particularly interested in the synthesis and structural studies of transition metal complexes, both in solid state and in solution. The metal complexes have been characterized by means of several spectroscopic techniques (NMR,

MoleculesMolecules 2021 2021, 26,, 26x FOR, x FOR PEER PEER REVIEW REVIEW 3 of3 16of 16

Molecules 2021, 26, 5014 2. Results2. Results 3 of 15 In Inher her career, career, Luciana Luciana Naldini Naldini was was particul particularlyarly interested interested in inthe the synthesis synthesis and and struc- struc- turaltural studies studies of oftransition transition metal metal complexes, complexes, both both in insolid solid state state and and in insolution. solution. The The metal metal complexescomplexes have have been been characterized characterized by by means means of ofseveral several spectroscopic spectroscopic techniques techniques (NMR, (NMR, IR, UV-Vis, EPR), XPS, single-crystal X-ray diffraction, as well as potentiometric and IR,IR, UV-Vis, UV-Vis, EPR), EPR), XPS, XPS, single-crystal single-crystal X-ray X-ray diffraction, diffraction, as aswell well as aspotentiometric potentiometric and and elec- elec- electrochemical analyses. trochemicaltrochemical analyses. analyses. The research was mainly addressed towards complexes with transition metal ions TheThe research research was was mainly mainly addressed addressed towards towards complexes complexes with with transition transition metal metal ions ions such as Cu(II), Co(II), Rh(II), and Au(0/I) and ligands of biological interest and therapeutic such as Cu(II), Co(II), Rh(II), and Au(0/I) and ligands of biological interest and therapeutic activity.such as In Cu(II), this ﬁeld, Co(II), dimeric Rh(II), Cu(II) and Au(0/I) [14,15] andand Rh(II)ligands complexes of biological [16] interest have been and synthesized therapeutic activity. In this field, dimeric Cu(II) [14,15] and Rh(II) complexes [16] have been synthe- withactivity. antibiotic In this trimethoprim field, dimeric or pyrimethamineCu(II) [14,15] and neutral Rh(II) molecules complexes that [16] behave have as been monoden- synthe- sized with antibiotic trimethoprim or pyrimethamine neutral molecules that behave as tatesized ligands with throughantibiotic a pyrimidinictrimethoprim nitrogen or pyrimethamine atom toward neutral the metal molecules center. In that particular, behave aas monodentatemonodentate ligands ligands through through a pyrimidinica pyrimidinic ni trogennitrogen atom atom toward toward the the metal metal center. center. In In species containing a squared Cu2(OMe)2 core in which the metals are held together by two particular,methoxoparticular, bridgesa speciesa species (Figure containing containing1a), and a asquareda dinuclearsquared Cu Cu rhodium2(OMe)2(OMe)2 core lantern-type2 core in inwhich which complex the the metals metals with are acetateare held held togetherbridgestogether by (Figure by two two 1methoxob) methoxo have beenbridges bridges obtained. (Figure (Figure 1a) 1a), and, and a dinuclear a dinuclear rhodium rhodium lantern-type lantern-type com- com- plexplex with with acetate acetate bridges bridges (Figure (Figure 1b) 1b) have have been been obtained. obtained.

(a)( a) (b)( b) Figure 1. Molecular structure of Cu(II) and Rh(II) complexes with antibiotic trimethoprim molecule: FigureFigure 1. 1.Molecular Molecular structure structure of of Cu(II) Cu(II) and and Rh(II) Rh(II) complexes complexes with with antibiotic antibiotic trimethoprim trimethoprim molecule: molecule: (a) from [15]; (b) from [16]. (H atoms omitted for clarity). (a()a from) from [15 [15]]; (b; )(b from) from [16 [16]]. (H. (H atoms atoms omitted omitted for for clarity). clarity).

InIn Inaddition, addition, addition, monomeric monomeric monomeric complexes complexes complexes of of ofCo(II) Co(II) Co(II) with with with trimethoprim trimethoprim trimethoprim have have have also also also been been been syn- syn- syn- thesizedthesizedthesized [17], [ 17[17],], and and and interesting interestinginteresting crystal crystalcrystal structur structuresstructures eshave have been been determined determined determined with with with aminobenzo- aminobenzo- aminoben- atezoateate derivative derivative derivative ligands, ligands, ligands, [Cu(bipy)(p-NH [Cu(bipy)(p-NH2-benzoato)]2-benzoato)]-benzoato)] [18], [18], [18 with], withwith o- o o-and- andand pp-nitrobenzoate, -nitrobenzoate,p-nitrobenzoate, [Cu(PPh[Cu(PPh[Cu(PPh3)32)(NO32)(NO2(NO2-benzoate)]22-benzoate)]-benzoate)] [19], [[19],19 ],as as aswell wellwell as as aswith withwith nitrophenols nitrophenolsnitrophenols [14]. [ 14[14]. ]. TheseTheseThese studies studies studies were were were extended extended extended to to tothe the the interact interaction interactionion of of ofhistamine histamine histamine (H2)-receptor (H2)-receptor (H2)-receptor antagonists, antagonists, antagonists, namelynamelynamely the the the anti-ulcerative anti-ulcerative anti-ulcerative drugs drugs cimetidine,cimetidine, cimetidine, famotidine, famotidine, famotidine, and and and ranitidine, raniti ranitidine,dine, with with platinumwith platinum platinum and 1 andpalladiumand palladium palladium [20 ],[20], studied[20], studied studied by byH-NMR by 1H-NMR 1H-NMR and and potentiometric and potentiometric potentiometric titration, titr titration,ation, but but also but also with also with copper with copper copper [21], [21],of[21], which of ofwhich which the structuralthe the structural structural study study indicatesstudy indicates indicates the tetradentate the the tetradentate tetradentate ligand ligand wrapped ligand wrapped wrapped around around thearound almost the the almostsquarealmost square planar square planar metal planar metal center metal center (Figure center (Figure2 (Figure). 2). 2).

Figure 2. Molecular structure of the square planar cationic copper(II) complex with 5- methylcimetidine modiﬁed by methanolic solvolysis of the nitrilic function [21]. (Perchlorate anion not shown for clarity).

It is interesting to note that the use of phosphine ligands has been often a distinctive

feature of her studies. The cubane-like [Cu(PPh3)(C≡CPh)]4 tetramer was obtained by Molecules 2021, 26, x FOR PEER REVIEW 4 of 16

Figure 2. Molecular structure of the square planar cationic copper(II) complex with 5-methylcimetidine modified by methanolic solvolysis of the nitrilic function [21]. (Perchlorate anion not shown Molecules 2021, 26, 5014 for clarity). 4 of 15

It is interesting to note that the use of phosphine ligands has been often a distinctive feature of her studies. The cubane-like [Cu(PPh3)(C≡CPh)]4 tetramer was obtained by treatmenttreatment of of [Cu(PPh [Cu(PPh3)23BH)2BH4]4 with] with phenylacetylene phenylacetylene and and KOH KOH (molar (molar ratio ratio 1/1/1) 1/1/1) in in ben- ben- zene/benzylzene/benzyl alcohol alcohol medium. medium. It It consists consists of of a tetrahedrala tetrahedral skeleton skeleton of of metal metal atoms atoms bonded bonded toto four four terminal terminal phosphine phosphine molecules molecules and and to to four fourµ-3-bridging μ-3-bridging phenylacetylide phenylacetylide ligands ligands whichwhich behave behave essentially essentially as as two-electron two-electron donors donors (Figure (Figure3)[ 3)22 ].[22].

FigureFigure 3. Scheme3. Scheme of of the the [Cu(PPh [Cu(PPh3)(C3)(C≡CPh)]≡CPh)]4 4tetramer tetramer complex complex [ 22[22]]. .

However,However, the the study study of of gold gold clusters clusters represents represents a significanta significant part part of of the the research research work work ofof Naldini Naldini and and coworkers, coworkers, which which started started at at the th Universitye University of of Milan Milan where where gold-phosphine gold-phosphine clustersclusters were were first first reported reported in in 1965 1965 by by reacting reacting PPh PPh3AuCl3AuCl with with sodium sodium borohydride borohydride [23 [23].]. ItIt is is worth worth noting noting that that in in previous previous experiments experiments with with copper copper and and silver silver complexes, complexes, the the [(PPh[(PPh3)23M(BH)2M(BH4)]4)] (M (M = Cu,= Cu, Ag) Ag) species species were were formed, formed, while while gold gold complexes complexes manifested manifested a dif- a . ferentdifferent behavior, behavior, leading toleading a red crystalline to a red precipitate. crystalline At theprecipitate. time, the Au At5(PPh the3) 4Cltime,5H 2Othe formulationAu5(PPh3)4 wasCl.5H believed2O formulation for this redwas compound believed for [24 ].this It wasred notcompound apparent [24]. until It thewas partial not ap- crystalparent structure until the of partial [Au11 (PPhcrystal3)7 (SCN)structure3] was of [Au reported11(PPh3 in)7(SCN) 1969 [325] was] that reported the structures in 1969 of [25] thethat species the structures formed were of the more species complex formed than we formerlyre more complex believed than and formerly comprising believed gold(0)- and gold(I)comprising bonds. gold(0)-gold(I) Following these bonds. results, Following the research these in this results, field the was research expanded in bythis using field the was . diphenylexpanded ethyl by phosphineusing the todiphenyl obtain [(PPhethyl2 Et)phosphine2Au3Cl Hto2 O]obtain4 and [(PPh [(PPh22Et)Et)2Au4Au3Cl6Cl]Y.H2O] (Y4 and = ClO[(PPh4, PF2Et)6, BPh4Au46Cl]Y), [26 ](Y thus = ClO leading4, PF6, toBPh novel4), [26] cluster thus structures.leading to novel cluster structures. SinceSince then, then, many many gold gold cluster cluster compounds compounds have have been been prepared prepared using using diphosphines, diphosphines, for example reduction of [(AuCl) (dppe)] by NaBH in ethanol gave the [Au (dppe) Cl ] for example reduction of [(AuCl)2 2(dppe)] by NaBH4 4 in ethanol gave the [Au6 6(dppe)2 22Cl2] cluster [26], and reduction of [Au(L)(NO )] featured [Au L ]3+, where L = PPh or P(p- cluster [26], and reduction of [Au(L)(NO3 3)] featured [Au9 89L8]3+, where L = PPh3 3 or P(p- tolyl) [27,28]. tolyl)3 3 [27,28]. The accurate structure of the [Au (PPh ) ]3+ cluster exhibits a crystallographic D and The accurate structure of the [Au9 9(PPh3 8 3)8]3+ cluster exhibits a crystallographic2 D2 and approximate molecular D h skeletal symmetry derived from an icosahedron (Figure4). The approximate molecular2 D2h skeletal symmetry derived from an icosahedron (Figure 4). compound has been extensively studied, as the reasons for research being carried out on The compound has been extensively studied, as the reasons for research being carried out this specific cluster are the availability and low cost of PPh3 along with the ease of cluster on this specific cluster are the availability and low cost of PPh3 along with the ease of synthesis. In fact, this species, deposited and activated on TiO2 and SiO2, has been explored cluster synthesis. In fact, this species, deposited and activated on TiO2 and SiO2, has been in catalytic reactions [29] and can undergo transformations to form additional clusters. explored in catalytic reactions [29] and can undergo transformations to form additional Indeed, a few years later, [Au (PPh ) ]3+ was treated with an excess of phosphine in clusters. 9 3 8 methanol and precipitated as [Au8(PPh3)8](aliz)2, (aliz = dializarinsulphonate), by addition Indeed, a few years later, [Au9(PPh3)8]3+ was treated with an excess of phosphine in of diethyl ether, thus giving rise to a new class of gold cluster compounds [30]. The methanol and precipitated as [Au8(PPh3)8](aliz)2, (aliz = dializarinsulphonate), by addition molecular structure of the cluster shows a centered gold atom connected to seven Au(PPh ) of diethyl ether, thus giving rise to a new class of gold cluster compounds [30]. The mo-3 moieties [31]. lecular structure3+ of the cluster shows a centered gold atom connected to seven Au(PPh3) [Au9(PPh3)8] was also reacted with KI in acetone to give [Au4(PPh3)4(µ-I)2], the moieties [31]. first tetranuclear gold structure to be reported. The molecular structure shown in Figure5 presents a crystallographic C2 symmetry with two edge bridging iodine ligands at opposite edges of the metal tetrahedron [32].

Molecules 2021, 26, x FOR PEER REVIEW 5 of 16

Molecules 2021, 26, 5014x FOR PEER REVIEW 5 of 1516

(a) (b)

2+ Figure 4. (a) Molecular structure of the [Au8(PPh3)8] core [30] (only PPh3 phosphorous atom are shown in the central part, dializarinsulphonate counterions not shown). (b) Molecular structure of the cationic [Au9(PPh3)8]3+ core [31] (for sake of clarity phenyl rings of PPh3 not shown). (a) (b) [Au9(PPh3)8]3+ was also reacted with KI in acetone to give [Au4(PPh3)4(μ-I)2], the first Figure 4. (a) Molecular structure of the [Au8(PPh3)8]2+ core [30] (only PPh3 phosphorous atom are shown in the central Figure 4. (a) Molecular structuretetranuclear of the [Au gold(PPh structure) ]2+ core to [ 30be] (onlyreported. PPh Thephosphorous molecular atom structure are shown shown in the in Figure central 5 pre- 8 3 8 3 3+ part, dializarinsulphonate counterions not shown). (b) Molecular structure of the cationic [Au9(PPh3)8]3+ core [31] (for sake part, dializarinsulphonate counterionssents a crystallographic not shown). (b) Molecular C2 symmetry structure with of the two cationic edge [Aubridging9(PPh3 )iodine8] core ligands [31] (for at sake opposite of clarity phenyl rings of PPh3 not shown). of clarity phenyl rings of PPhedges3 not shown). of the metal tetrahedron [32].

[Au9(PPh3)8]3+ was also reacted with KI in acetone to give [Au4(PPh3)4(μ-I)2], the first tetranuclear gold structure to be reported. The molecular structure shown in Figure 5 presents a crystallographic C2 symmetry with two edge bridging iodine ligands at opposite edges of the metal tetrahedron [32].

FigureFigure 5. 5.Molecular Molecular structure structure of of [Au [Au4(PPh4(PPh3)34)4((µμ-I)-I)22],], (from(from [[32]32];; H H atoms atoms omitted omitted for for clarity). clarity).

AA study study in in solution solution was was also also conducted conducted on on (PPh (PPh3)Au(C3)Au(C≡≡CPh)CPh) complexes complexes by by NMR, NMR, ... indicating that contrary to the solid state ﬁndings [33], the existence of Au … Au contacts indicating that contrary to the solid state findings [33], the existence of Au Au contacts in insolution solution can can be be excluded, excluded, being being solvation solvation effect effectss likely likely stronger stronger than than intermolecular intermolecular gold Figure 5. Molecular structure of [Au4(PPh3)4(μ-I)2], (from [32]; H atoms omitted for clarity). goldcontacts contacts [34]. [In34 ].another In another experiment, experiment, the reaction the reaction of (PPh of3)AuCl (PPh3 )AuClwith cimetidine with cimetidine in an al- inkaline an alkaline medium medium under undermild conditions mild conditions led to a led complex to a complex (Figure (Figure 6), comprising6), comprising a thiolato a A study in solution was also conducted on (PPh3)Au(C≡CPh) complexes by NMR, thiolatoligand ligandresulting resulting from cleavage from cleavage of one of of one the of thioether the thioether bonds bonds of cimetidine of cimetidine [35], [ 35thus], indicating that contrary to the solid state findings [33], the existence of Au…Au contacts in thusdemonstrating demonstrating a different a different behavior behavior by the by theheavier heavier gold gold atom atom with with respect respect to copper to copper (see solution can be excluded, being solvation effects likely stronger than intermolecular gold (seeabove). above). contacts [34]. In another experiment, the reaction of (PPh3)AuCl with cimetidine in an alkaline medium under mild conditions led to a complex (Figure 6), comprising a thiolato ligand resulting from cleavage of one of the thioether bonds of cimetidine [35], thus demonstrating a different behavior by the heavier gold atom with respect to copper (see above).

Molecules 2021, 26, 5014 6 of 15 MoleculesMolecules 20212021,, 2626,, xx FORFOR PEERPEER REVIEWREVIEW 66 ofof 1616

FigureFigureFigure 6. 6.6. The The PPhPPh333 goldgold complexcomplex obtainedobtained withwith thethe modiﬁedmodifiedmodified cimetidinecicimetidinemetidine ligandligand [[35][35]35]...

InInIn orderorderorder tototo elucidateelucidateelucidate thethethe mechanismmechanismmechanism of ofof thethethe observed observedobserved C-S C-SC-S bond bondbond cleavage, cleavage,cleavage, Naldini NaldiniNaldini and andand coworkerscoworkerscoworkers reactedreactedreacted (PPh(PPh(PPh333)Au(NO)Au(NO33)) with with benzylbenzyl phenylphenylphenyl sulﬁdesulfidesulfide (PhCH(PhCH(PhCH222-S-Ph)-S-Ph) ininin KOHKOHKOH atatat − - ambientambientambient temperature.temperature.temperature. TheTheThe X-ray X-rayX-ray diffraction diffractiondiffraction study studystudy of ofof the thethe obtained obtainedobtained product, product,product, as asas a a BFa BFBF4 44- salt,salt,salt, 2+ revealed the formation of the cluster [(PPh ) Au O ] 2+2+ as having a chair conﬁguration and revealedrevealed thethe formationformation ofof thethe clustercluster [(PPh[(PPh3 336))66AuAu666OO666]] asas havinghaving aa chairchair configurationconfiguration andand crystallizingcrystallizingcrystallizing inin aaa unitunitunit cellcellcell ofofof comparable comparablecomparable parameters parametersparameters as asas those thosethose reported reportedreported [ 36[36].[36].]. Complexes ComplexesComplexes with the hexanuclear Au L core, where gold atoms adopt the edge-shared bi-tetrahedral withwith thethe hexanuclearhexanuclear AuAu666LL666 core,core, wherewhere goldgold atomsatoms adoptadopt thethe edge-sharededge-shared bi-tetrahedralbi-tetrahedral structurestructurestructure and andand in inin an anan averageaverageaverage oxidation oxidationoxidation state statestate between betwbetweeneen 0 00 and andand 1, 1,1, have havehave been beenbeen widely widelywidely studied, studied,studied, as asas for example [Au (PPh ) ](NO ) [37], [(AuPPh ) (NNR ) ] with R = Me, or Ph [38], and forfor exampleexample [Au[Au666(PPh(PPh333))66](NO](NO33))222 [37],[37], [(AuPPh[(AuPPh333))66(NNR6(NNR22))22]] 2 withwith RR == Me,Me, oror PhPh [38],[38], andand [Au (dppp) ](NO ) [39]. [Au66(dppp)4](NO33)22 [39]. [Au6(dppp)4](NO3)2 [39]. 2+ The [(PPh3)6Au6(OH)2]2+ cluster, (Figure7), synthesized by Naldini was reported in TheThe [(PPh[(PPh33))66AuAu66(OH)(OH)22]]2+ cluster,cluster, (Figure(Figure 7),7), synthesizedsynthesized byby NaldiniNaldini waswas reportedreported inin her student’s thesis [12], but single crystals were of poor quality for suitable X-ray structural herher student’sstudent’s thesisthesis [12],[12], butbut singlesingle crystalscrystals werewere ofof poorpoor qualityquality forfor suitablesuitable X-rayX-ray struc-struc- analysis. However, it was observed that: (i) all the Au ... Au distances were within the turaltural analysis.analysis. However,However, itit waswas observedobserved that:that: i)i) allall thethe AuAu……AuAu distancesdistances werewere withinwithin thethe same order of magnitude; (ii) a prolonged reaction at higher temperature (>50 ◦C) led samesame orderorder ofof magnitude;magnitude; ii)ii) aa prolongedprolonged reactionreaction atat higherhigher temperaturetemperature (>50(>50 °C)°C) ledled toto aa to a dark orange-red solution, characteristic of polynuclear gold clusters, indicating the darkdark orange-redorange-red solution,solution, characteristiccharacteristic ofof polynuclearpolynuclear goldgold clusters,clusters, indicatingindicating thethe possi-possi- possible partial reduction of gold to Au(0), the number of coupling being determined by bleble partialpartial reductionreduction ofof goldgold toto Au(0),Au(0), thethe numbernumber ofof couplingcoupling beingbeing determineddetermined byby kinet-kinet- kinetics factors. icsics factors.factors.

Figure 7. Naldini’s notes on the [(PPh ) Au (OH) ]2+ cluster with her signature (from ref [12]). 3 6 6 22+ FigureFigure 7.7. Naldini’sNaldini’s notesnotes onon thethe [(PPh[(PPh33))66AuAu66(OH)(OH)22]]2+ clustercluster withwith herher signaturesignature (from(from refref [12][12]).).

Molecules 2021, 26, 5014 7 of 15 Molecules 2021, 26, x FOR PEER REVIEW 7 of 16

WithWith this this in in mind, mind, the the presence presence of of two two Au(0) Au(0) atoms atoms out out of of six six was was postulated, postulated, with with thethe presence presence of of two two OH OH- -anions anions replacing replacing the the oxo oxo groups groups indicated indicated by by other other research research 1 groupsgroups [36 [36,40],,40], since since the the energy energy gain gain due due to theto the two two s electrons s1 electrons should should compensate compensate for the for repulsionthe repulsion of ions of ofions the of same the same charge. charge. Numerous Numerous exchange exchange reactions reactions were were performed performed in - - orderin order to obtain to obtain crystals crystals of good of good quality, quality, and the and derivatives the derivatives with NO with3 and NO BF3- 4andcounterions BF4- coun- wereterions structurally were structurally characterized characterized by single by crystal single X-ray crystal diffraction X-ray diffraction analysis. analysis. However, How- in someever, cases,in some the nucleophiliccases, the nucleophilic anions led toanions the correspondent led to the correspondent mononuclear mononuclear (PPh3)AuX complex(PPh3)AuX (Scheme complex2). The (Scheme organometallic 2). The organometallic complex (PPh 3complex)AuPh, obtained(PPh3)AuPh, by extraction obtained ofby - phenylextraction group of phenyl from the group B(Ph) from4 anion, the B(Ph) was structurally4- anion, wascharacterized structurally characterized by X-ray diffraction by X-ray bydiffraction Hong et al.by [Ho41].ng et al. [41].

Scheme 2. Reaction scheme of the complex [(PPh3)6Au6(OH)2](NO3)2 with different anions. Scheme 2. Reaction scheme of the complex [(PPh3)6Au6(OH)2](NO3)2 with different anions.

TheThe presence presence of of hydroxyl hydroxyl groups groups in in [(PPh [(PPh3)63Au)6Au6(OH)6(OH)2](NO2](NO3)32)2cluster cluster was was supported supported 1 1 byby a a seriesseries ofof detailed experiments [12]. [12]. The The H HNMR NMR spectrum spectrum in CD in CD2Cl2 Clshowed2 showed a com- a complexplex pattern pattern centered centered at at7.45 7.45 ppm ppm for for the the phosphine phosphine protons protons and a singlet atat ca.ca. 22 ppm, ppm, withwith a a 90:290:2 intensityintensity ratio.ratio. Due Due to to possible possible er errorsrors in in the the OH OH assignment assignment for for the the great great dis- disproportionproportion of of the the number number of of protons, protons, the the te testst was comforted byby thethe subsequentsubsequent addition addition 17 ofof D D2O2O that that led led to to the the disappearance disappearance of of the the peak peak at at 2 2 ppm. ppm. The The 17OO NMR NMR spectrum spectrum showed showed threethree singlets singlets at at− −12.312,12.312, 6.0486.048 andand 28.08028.080 ppm,ppm, which which can can be be assigned assigned to to water, water, ethanol ethanol (as(as the the internal internal standard), standard), and and OH OH- groups,- groups, respectively. respectively. A A coulombometric coulombometric reduction reduction of of aa solution solution of of [(PPh[(PPh33))66Au6(OH)(OH)22](NO](NO3)32),2 performed, performed at at −1.50−1.50 Volt Volt vs. vs.SCE, SCE, involved involved the thecon- consumptionsumption of 4.05 of 4.05 electrons/mol; electrons/mol; a result a result likely likely confirming conﬁrming the presence the presence of four of Au(I) four Au(I)atoms atomsout of out six. of Mass six. spectrometry Mass spectrometry revealed revealed peaks peaksat 2789 at (calcd 2789 (calcd2789.6) 2789.6) and 1394 and (calcd 1394 (calcd1394.7) + + 1394.7)for the for cations the cations [(PPh [(PPh3)6Au63(OH))6Au26](OH)+ and2 ][(PPhand3) [(PPh3Au3(OH)]3)3Au+,3 (OH)]respectively,, respectively, and no andpeak no at + peak1393 at correspondent 1393 correspondent to [(PPh to3) [(PPh3Au3O]3)3+Au [12].3O] [12]. InIn addition, addition, thethe XPSXPS characterization [42] [42] of of the the electronic electronic structure structure of ofthe the cluster cluster un- underder study study showed showed two two peaks peaks in inthe the region region of ofthe the 4f gold 4f gold electrons, electrons, at 85.8 at 85.8 (for (for Au(I)) Au(I)) and and83.9 83.9 eV eV(for (for Au(0)) Au(0)) associated associated to toa apeak peak area area of of 2:1 2:1 (thus (thus to a 4:24:2 ratio).ratio). ThreeThree peaks, peaks, at at 531.5,531.5, 532.7, 532.7, and and 530.2 530.2 eV, eV, were were found found in thein the 1s oxygen 1s oxygen electron electron region, region, assigned assigned to the to OH, the nitrate,OH, nitrate, and diphenyl and diphenyl ether groups.ether groups. TheThe analogous analogous complexcomplex having SH SH groups groups replacing replacing the the hydroxyl hydroxyl ones ones was was also also pre- prepared by Naldini, [(PPh ) Au (SH) ](NO ) [12]. It is worth noting that Naldini and pared by Naldini, [(PPh3)36Au6 6(SH)6 2](NO2 3)23 [12].2 It is worth noting that Naldini and coworkerscoworkers prepared prepared plentyplenty ofof similar gold cl clusters,usters, also also with with mixed-metals, mixed-metals, for for which which no nostructural structural information information is isavailable. available. At Atthat that time, time, the the lack lack of ofan aneasy easy X-ray X-ray facility facility or orthe thedifficultly difﬁcultly to toobtain obtain suitable suitable crystals crystals for for diffraction diffraction analysis analysis delayed delayed the the development development of of the study, and the structure, as well as the formulation of these complexes, could be the study, and the structure, as well as the formulation of these complexes, could be only only hypothesized. In support of these hypotheses, the presence of µ3-OH species in gold hypothesized. In support of these hypotheses, the presence of μ3-OH species in gold clus- cluster cations and their equilibria in wet solution have been reported a few years ago [43]. ter cations and their equilibria in wet solution have been reported a few years ago [43]. All the Au8, Au9, and Au11 clusters show a central chair-like hexagon, thus the Au6L6 All the Au8, Au9, and Au11 clusters show a central chair-like hexagon, thus the Au6L6 system can be considered as a starting building block for the construction of clusters of system can be considered as a starting building block for the construction of clusters of higher nuclearity [30] (Figure8). higher nuclearity [30] (Figure 8).

Molecules 2021, 26, 5014 8 of 15 Molecules 2021, 26, x FOR PEER REVIEW 8 of 16

Figure 8. The Au8, Au9, and Au11 clusters comprising a central chair-like hexagon [30]. Figure 8. The Au8, Au9, and Au11 clusters comprising a central chair-like hexagon [30]. 3.3. RecentRecent AdvancesAdvances InIn thethe lastlast years,years, afterafter severalseveral decadesdecades havehave passedpassed sincesince the the outstanding outstanding work work from from NaldiniNaldini andand coworkers,coworkers, thethe chemistrychemistry ofof goldgold clustersclusters hashas reachedreached aa notablenotable degreedegree ofof complexity,complexity, dealing dealing with with new new materials materials possessing possessing interesting interesting physico-chemical physico-chemical properties, proper- suchties, assuch luminescence as luminescence [44–47 [4],4–47], chirality chirality [48], or [48], paramagnetic or paramagnetic behavior behavior [49]. In [49]. the In mare the magnummare magnum of gold of complexes,gold complexes, clusters, clusters, nanoclusters, nanocluste andrs,nanoparticles and nanoparticles so numerously so numer- reportedously reported in the literature,in the literature, which which have already have al beenready reviewed been reviewed [50–53 ],[50–53], we decided we decided to focus to thefocus second the second part of part this of paper this paper on some on some recent recent compounds compounds with with remarkable remarkable features, features, to brieflyto briefly highlight highlight the the progress progress made made in this in this field, field, the latestthe latest achievements, achievements, and and above above all the all currentthe current trends trends in research. in research. 3.1. Superatom Gold Cluster Complexes 3.1. Superatom Gold Cluster Complexes The most recent studies range from small molecular-like species to larger nanoparticle- The most recent studies range from small molecular-like species to larger nanoparti- like clusters with hundreds of metal atoms. Contrary to classical nanoparticles, such cle-like clusters with hundreds of metal atoms. Contrary to classical nanoparticles, such nanoclusters, with a core size smaller than 2 nm, have a definite molecular structure and nanoclusters, with a core size smaller than 2 nm,z have a definite molecular structure and thus a precise molecular formula, of the [AunLm] kind (where L is the protecting ligand, thus a precise molecular formula, of the [AunLm]z kind (where L is the protecting ligand, and z is the net charge of the metal) [54], conferring them molecule-like physical and and z is the net charge of the metal) [54], conferring them molecule-like physical and chemical properties. Meanwhile, the electronic shell closing, geometry, and the staple motif chemical properties. Meanwhile, the electronic shell closing, geometry, and the staple mo- can be tuned with single-atom precision. tif can be tuned with single-atom precision. Special attention has been posed to the stabilization and protection of Au clusters, as Special attention has been posed to the stabilization and protection of Au clusters, as the outermost layer of these structures interacts with the external environment, determining theirthe outermost characteristics layer (e.g.,of these chirality, structures optical intera absorption,cts with the photoluminescence, external environment, hydrodynamic determin- size,ing their etc.) andcharacteristics the possibility (e.g., of chirality, application optical in different absorption, research photoluminescence, areas, for example, hydrody- electron- icsnamic [55, 56size,], catalysis etc.) and [57 the–59 possibility], and the of biomedical application field in different (drug and research gene delivery, areas, for biosensors, example, photothermalelectronics [55,56], and photodynamic catalysis [57–59], therapy, and imaging,the biomedical cancer field treatment, (drug etc.)and [60gene–64 ].delivery, biosensors,Among photothermal the commonly and employed photodynamic ligands for th monolayer-protectederapy, imaging, cancer gold treatment, nanoclusters, etc.) phosphines[60–64]. were historically the most frequently used, leading to Au clusters of various sizes andAmong structures. the commonly More recently employed (especially ligands in for the monolayer-protected past two decades), thiolates gold nanoclusters, (SR) have phosphines were historically the most frequently used, leading to Au clusters of various emerged as precious ligands in the preparation of Aun(SR)m clusters, because the strong sulfur-Ausizes and structures. bonds and More the aurophilic recently (especially interactions in amongthe past gold two atomsdecades), determine thiolates their (SR)high have stabilityemerged [50 as,65 precious,66] in solution ligands andin the subsequently preparation their of Au possiblen(SR)m applications.clusters, because Other the organic strong ligandssulfur-Au that bonds have and been the used aurophilic to produce interactio atomicallyns among precise gold Au atoms clusters determine are selenolates, their high tellurolates,stability [50,65,66] N-heterocyclic in solution carbenes and subsequently (NHCs), and their alkynes possible [54]. applications. Other organic ligandsGold that is a have suitable been metal used to to build produce stable atom nanostructures,ically precise although Au clusters small clustersare selenolates, tend to betellurolates, more reactive. N-heterocyclic Their shape carbenes can vary (NHCs), greatly, fromand alkynes the flat flakes[54]. of clusters with less than 12 atomsGold to is spherical a suitable or spheroidalmetal to build structures stable whennanostructures, the overall although number of small valence clusters electrons tend isto equal be more or close reactive. to a “magic”Their shape value, can given vary bygreatly, the n* from = 2(L the + 1)flat2 rule, flakes where of clusters L is an with integer. less Thethan relative 12 atoms values to spherical (2, 8, 18, 32,or 50,spheroidal 72, etc.) coincidestructures with when the the number overall of electronsnumber of necessary valence toelectrons fill the orbitalsis equal inor theclose electron to a “mag shellsic” ofvalue, an atom, given andby the in fact,n* = a2(L spherical + 1)2 rule, gold where cluster L is canan integer. be considered The relative as a noble-gas values (2, superatom 8, 18, 32, 50, [67 72,], leadingetc.) coincide to closed-shell with the configurations:number of elec- [Stronsσ]2; [Snecessaryσ]2[Pσ]6 ;to [S fillσ]2 [Ptheσ ]orbitals6[Dσ]10 ;in etc. the As electron evidence, shells clusters of an with atom, 18 and electrons in fact, (L a =spherical 2) with

Molecules 2021, 26, 5014 9 of 15

filled S, P, and D molecular orbitals are remarkably robust [68]. When Au clusters adopt non-spherical geometries the degeneracy of the Pσ shell is removed, leading to [Sσ]2[Pσ]2 and [Sσ]2[Pσ]4 configurations for prolate and oblate distortions, respectively, due to the high energy gap among the P molecular orbitals which favors the stabilization of closed sub-shell electronic structures. Examples of this are the gold clusters with phosphines as t 2+ σ 2 2+ 2+ the ligands: [Au4(P Bu3)4] of spherical shape ([S ] ), [Au6(PPh3)6] and [Au6(dppp)4] σ 2 σ 2 + σ 2 σ 4 prolate ([S ] [P ] ), [Au7(PPh3)7] oblate ([S ] [P ] )[13] are representative examples of gold clusters with phosphines ligands that verify this simple analysis. Most of the reported superatom clusters are heterometallic gold structures “doped” with other noble metals (Ag, Cu, Pt, Pd, Ir, etc.) (see for instance [69]) or intermetallic species; nevertheless, several homometallic gold clusters stabilized by different ligands have been published. In this case, the “magic number” may vary according to the electron-withdrawing ability of the ligands, and is better described by the formula n* = NvX − M − z, where N is the number of core metal atoms (X), vX the atomic valence, M the number of electron-localizing (or electron-withdrawing) ligands, and z the overall charge on the complex. Thus, extraordinary stability is associated with a total electron count of n* = 2, 8, 18, 34, 58, 92, 138 ... [67]. Occasionally, 20 and 40 electrons can also lead to stable clusters [70]. Relatively to low n*, Au13 superatom complexes protected by N-heterocyclic carbene ligands were studied, showing that their structures are formed by an icosahedral Au13 core with nine NHC ligands and three chlorides symmetrically arranged around [71]. This arrangement favors the formation of multiple CH-π and π-π interactions, as confirmed by crystallographic analyses, which stiffen the ligand and probably promote the extraordinar- ily high photoluminescent quantum yields (vide infra) of these complexes (up to 16.0%, a value which is remarkably higher than that of the most luminescent ligand-protected Au13 clusters). DFT calculations suggest an 8-electron superatom configuration for these kinds of complexes. A slightly different structure with a closed electronic shell (again 8 electrons) is rep- 2+ resented by the hydride-doped gold superatom (Au9H) , a nearly spherical cluster, as 3+ revealed by DFT calculations, obtained by inserting a hydride anion into [Au9(PPh3)8] , which is a 6-electron oblate gold cluster with a coordinatively unsaturated site, to give the 2+ − 8-electron [Au9H(PPh3)8] species [72]. The H anion with its two 1s electrons contributes to the superatomic electron count, giving a [S]2[P]6 configuration. The hydride can be displaced by an Au-Cl fragment, and the subsequent addition of a second Au-Cl group 3+ leads to the formation of the Au11 cluster, with the same number of valence electrons. Transformation of a non-superatom into a superatom nanocluster was obtained also − in the case of the thiolate-protected cluster [Au23(SC6H11)16] which was converted into Au36(TBBT)24 (TBBT = 4-tertbutylbenzenethiolate) via Au28(TBBT)20 formation, by using the ligand exchange-induced size/structural transformation (LEIST) approach [73]. An analogous nanocluster, Au44(2,4-DMBT)26 (2,4-DMBT = 2,4-dimethylbenzenethiolate), is an 18 electron superatom possessing chiral properties, conferred by the peculiar arrangement of staples (bridging thiolates) and part of the Au29 kernel atom [74].

3.2. Chiral Gold Cluster Complexes The presence of a chiral element on a gold cluster can determine its potential applications in a number of fields, for instance, asymmetric catalysis, chiral recognition, or in chiroptical materials [75,76]. Such an element of chirality can be found either in the gold core or in the capping ligands, or both [77]. In the first case, (i) the structure of the metal skeleton is intrinsically chiral, or (ii) an inherently achiral core with a chiral shell is created by the symmetric disposition of surface- protecting units. Instead, in the latter case, chiral ligands confer chiroptical properties to the Au nanoclusters via vicinal effects or a chiral electrostatic field. When the chiral element is located inside the gold core itself, its inherent or intrinsic chirality is especially enthralling being different in nature with respect to that of Molecules 2021, 26, x FOR PEER REVIEW 10 of 16

Molecules 2021, 26, 5014 10 of 15

When the chiral element is located inside the gold core itself, its inherent or intrinsic chirality is especially enthralling being different in nature with respect to that of conven- conventionaltional chiral molecules. chiral molecules. The comprehension The comprehension and application and application of optical properties of optical proper-of chiral tiesgold of clusters chiral goldis still clusters a major is challenge, still a major due challenge, to scarce structural due to scarce evidence structural of enantiomeri- evidence ofcally enantiomerically pure Au nanostructures, pure Au nanostructures, with just a very withfew cases just a described very few in cases the literature. described The in thefirst literature. reported The species ﬁrst reported of this species kind, of this[Au kind,20(PP3) [Au4]Cl204, (PP(PP3)43]Cl =4, (PPtris(2-(diphe-3 = tris(2- (diphenylphosphino)ethyl)phosphine),nylphosphino)ethyl)phosphine), possesses possesses a C3 symmetric a C3 symmetric molecular molecular structure structure consisting con- sistingof a combination of a combination of an achiral of an achiral icosahedral icosahedral Au13 unit Au13 andunit a andhelical a helical Y-shaped Y-shaped Au7 motif, Au7 motif,which which confers confers chirality chirality to the towhole the whole structure structure (Figure (Figure 9) [78].9)[ 78].

4+4+ FigureFigure 9. 9.The The chiralchiral cation cation [Au [Au2020(PP(PP33)4]] (PP(PP3 3= =tris(2-(diphenylphosphino)ethyl)phosphine) tris(2-(diphenylphosphino)ethyl)phosphine) [78] [78.].

MoreMore recently, recently, an an inherently inherently chiral chiral Au Au2424framework framework with with a a nearly nearly spherical spherical shape shape and and highhigh stability stability due due to to its its 18-electron 18-electron system system was was prepared prepared in bothin both its enantiomericits enantiomeric forms forms by usingby using Chiraphos Chiraphos [2,3-bis(diphenylphosphino)butane] [2,3-bis(diphenylphosphino)butane] as theas the chiral chiral auxiliary. auxiliary. It contains It contains a squarea square antiprism-like antiprism-like octagold octagold (essentially (essentially achiral), achiral), twinned twinned by two by helicene-liketwo helicene-like hexagold hex- motifsagold [motifs79]. The [79]. inherent The inherent chirality chirality of the superatom of the superatom cluster residedcluster resided in the double-helical in the double- hexagoldhelical hexagold strands inducedstrands induced by the (R,R)- by the or (R,R)- (S,S)-diphosphines. or (S,S)-diphosphines. OtherOther examplesexamples ofof intrinsicallyintrinsically chiralchiral goldgold nanostructure nanostructure may may be be found found in in the the small small enantiomeric clusters with formulas [Au (R-/S-BINAP) ](CF COO) and [Au (R-/S- enantiomeric clusters with formulas [Au9 9(R-/S-BINAP)4 4](CF3 3COO)33 and [Au1010(R-/S- BINAP) (p-CF C H C≡C)](CF COO) [80]. The Au core has a C symmetry and is BINAP)44(p-CF33C6H44C≡C)](CF3COO)3 3 [80].3 The Au9 core9 has a C2 symmetry2 and is com- composed of two Au tetrahedra sharing an Au atom, and two additional Au atoms posed of two Au4 tetrahedra4 sharing an Au atom, and two additional Au atoms attached attachedon the opposite on the oppositeside, which side, can which be considered can be considered as a distorted as acrown distorted structure. crown Instead, structure. the Instead, the Au10 species has a very low symmetry (C1) due to an exterior Au atom Au10 species has a very low symmetry (C1) due to an exterior Au atom attached to one of attached to one of the corners of a tetrahedron. Both the couples of enantiomers show good the corners of a tetrahedron. Both the couples of enantiomers show good chiroptical prop- chiroptical properties. erties. 3.3. Luminescent Gold Cluster Complexes Luminescence is another characteristic of many gold cluster complexes, which could also be exploited to prepare OLEDs (organic electroluminescent devices) [81]. A typical behavior may be seen in the switch of color caused by the change in the solvent used to prepare a series decanuclear gold(I) µ3-sulﬁdo complexes with the generic formula 3 [Au10XPh2PN(CnH2n+1)PPh2}4(µ -S)4](ClO4)2 bearing alkyl chains of various lengths on the aminodiphosphine ligand [82]. These complexes tend to form supramolecular nanoag- gregate assemblies upon solvent modulation, whose photoluminescence colors can be

Molecules 2021, 26, x FOR PEER REVIEW 11 of 16

3.3. Luminescent Gold Cluster Complexes Luminescence is another characteristic of many gold cluster complexes, which could also be exploited to prepare OLEDs (organic electroluminescent devices) [81]. A typical behavior may be seen in the switch of color caused by the change in the solvent used to prepare a series decanuclear gold(I) μ3-sulfido complexes with the generic formula [Au10XPh2PN(CnH2n+1)PPh2}4(μ3-S)4](ClO4)2 bearing alkyl chains of various lengths on the aminodiphosphine ligand [82]. These complexes tend to form supramolecular nanoaggre- Molecules 2021, 26, 5014 gate assemblies upon solvent modulation, whose photoluminescence colors 11can of 15be switched from green to yellow and to red by using different solvent systems. This, in turn, causes substantial changes in the nanostructured morphology of such clusters, from switchedspherical fromto cubic green shape. to yellow and to red by using different solvent systems. This, in turn, causesIn the past substantial couple changesof years inor theso, nanostructuredsome luminescent morphology new Au clusters of such have clusters, been from pre- sphericalpared, the to most cubic interesting shape. being a series of small alkyl thiolato-protected Au complexes withIn general the past formula couple ofAu years2(SR) or2 and so, someAu3(SR) luminescent3 based on new the Au C4 clustersH9SAu have(1-butanethiol), been prepared,C6H13OSAu the most (6-mercapto-1-hexanol), interesting being a series C12H of25SAu small (1-dodecanethiol) alkyl thiolato-protected and C6H Au5SAu complexes (thiophe- withnol) units general [83]. formula They were Au2 (SR)formed2 and in a Au one-pot3(SR)3 reductionbased on of the tetrachloroaurate C4H9SAu (1-butanethiol), in the pres- Cence6H13 ofOSAu a threefold (6-mercapto-1-hexanol), excess of the thiolate C12H li25gands,SAu (1-dodecanethiol) and they all show and high C6 Hluminescence5SAu (thio- phenol)under UV units light, [83 which]. They is werelimited formed to the inrange a one-pot 550–700 reduction nm in solution, of tetrachloroaurate although a full in emis- the presencesion in the of arange threefold 550-850 excess nm ofwas the recorded thiolate ligands,for the solids and they using all different show high techniques. luminescence underRelatively UV light, small which polinuclear is limited tosulfido the range Au(I) 550–700 clusters, nm with in solution, formulas although [Au14S6(bdpp- a full emissionmapy)5]Cl in2 theand range [Au 550-85018S8(bdppmapy) nm was recorded6]Cl2, forwhere the solidsbdppmapy using different = N,N-bis-(diphe- techniques. nylphosphanylmethyl)-2-aminopyridineRelatively small polinuclear sulfido Au(I) (Figure clusters, 10), with are formulas very stable, [Au 14stronglyS6(bdppmapy) luminescent5]Cl2 andwith [Au a high18S8(bdppmapy) quantum yield,6]Cl2 ,good where solubility, bdppmapy low = N,N-bis-(diphenylphosphanylmethyl)-2-cytotoxicity, and have been exploited as aminopyridinelysosome trackers (Figure for 10live), arecell very imaging stable, [84]. strongly [Au14S luminescent6(bdppmapy) with5]2+ arepresents high quantum a new yield, clus- goodter skeleton-type solubility, low formed cytotoxicity, by an andAu6S have2(bdppmapy) been exploited unit and as lysosome an Au8S4 trackers(bdppmapy) for live4 crown cell 2+ imagingconnected [84 ].to [Aueach14 Sother6(bdppmapy) through 5Au] −representsS and aurophilic a new clusterinteractions. skeleton-type The Au6 formedS2 unit adopts by an Aua cubane6S2(bdppmapy) structure unit where and the an AuS atoms8S4(bdppmapy) are located4 crown across connected the body todiagonal each other of the through solid, Auand− Sthe and Au aurophilic atoms are interactions. bonded to The a P Auatom6S2 fromunit adopts the bottom a cubane bdppmapy, structure whereor capped the S with atoms an areAu located2S triangle. across Each the S body atom diagonal of the cluster of the solid,adopts and a thetriply Au bridging atoms are coordination bonded to a mode P atom to frombind the three bottom Au atoms bdppmapy, from orthe capped Au6S2 with cubane. an Au The2S triangle.18 gold Eachatoms S atomin [Au of18 theS8(bdppmapy) cluster adopts6]2+ aare triply connected bridging by coordination eight triply bridging mode to bindS atoms three and Au surrounded atoms from by the six Au bdppmapy6S2 cubane. ligands. The 2+ 18Both gold clusters atoms inare [Au air-stable18S8(bdppmapy) and emit6] brightare connected yellow-green by eight light triply (λem bridging 540 nm Sand atoms 518and nm, surroundedrespectively) by in six the bdppmapy solid state, ligands. with Bothcorres clustersponding are quantum air-stable andyields emit of bright20.7% yellow-greenand 26.6% at lightroom (λ temperature.em 540 nm and Their 518 nm,luminescence respectively) greatl in they enhanced solid state, cellular with correspondingimaging of lysosomes quantum in yieldsliving of cells, 20.7% with and long-term 26.6% at room tracking temperature. of lysosomes Their up luminescence to 36 h without greatly any enhanced evident cellular loss of imagingluminescence of lysosomes intensity. in living cells, with long-term tracking of lysosomes up to 36 h without any evident loss of luminescence intensity.

2+ 2+ Figure 10. [Au18S8(bdppmapy)6] (left) and [Au14S6(bdppmapy)5] (right) cations (bdppmapy = N,N-bis-(diphenylphosphanylmethyl)-2-aminopyridine, phenyl rings bound to P atoms not shown for clarity) [84].

4. Conclusions Nowadays plenty of papers, which addressed the relationships between the structures of clusters and their skeletal electron counts, have been reported, often citing Naldini’s gold structures. For example, we would like to mention a uniﬁed model developed to achieve a fundamental understanding of the stability of ligand-protected gold clusters [85], a theo- 2+ retical study of the electronic and optical properties of [Au8L8] species (where L = PH3, PPh3) using a density functional (DFT) approach and the time-dependent density func- Molecules 2021, 26, 5014 12 of 15

tional theory (TDDFT) [86], the description of triphenylphosphine-stabilized undecagold species [87], as well as a description of geometrical structures and unique optical properties of phosphine-coordinated cold clusters [88], to cite but a few. Recently, it was reported that gold phosphine complexes show anticancer activity towards a panel of different tumor cell lines [89]. In conclusion it is interesting to cite a theoretical approach of bonding patterns in gold clusters [13] where Mingos states that “The detailed electronic structures of metal clusters will eventually be tackled using increasingly accurate DFT MO calculations, but the presence of conceptual models ... will remain valuable for new generations of chemists, providing an important pedagogical introduction to inorganic structural chemistry”.

Author Contributions: Conceptualization, M.L.G., F.D. and E.Z.; writing—original draft preparation, M.L.G., S.M., F.D., E.Z., M.P. and M.A.Z.; input, writing—review and editing, M.L.G., F.D., A.P., E.Z., M.P., S.M. and M.A.Z. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Acknowledgments: For the drawing-up of the paper and support the authors thanks are due to colleagues of the University of Cagliari, G. Crisponi, V. M. Nurchi, and of the University of Sassari, G. Lubinu, and G. Rassu, who contributed to the research on metals and in particular gold chemistry in theory and or experiments. Conﬂicts of Interest: The authors declare no conﬂict of interest.

Abbreviations

aliz dializarinsulphonate bdppmapy N,N-bis-(diphenylphosphanylmethyl)-2-aminopyridine BINAP 2,20-bis(diphenylphosphino)-1,10-binaphthyl Chiraphos 2,3-bis(diphenylphosphino)butane DFT density-functional theory DMBT dimethylbenzenethiolate dppe diphenylphosphinoethane dppp diphenylphosphinopropane EPR electron paramagnetic resonance IR Infra-red spectroscopy LEIST ligand exchange-induced size/structural transformation NHC N-heterocyclic carbene NMR nuclear magnetic resonance PPh3 triphenylphosphine SCE saturated calomel electrode TBBT 4-tertbutylbenzenethiolate TDDFT time dependent density functional theory XPS X-ray photoelectron spectroscopy

References 1. Malatesta, L. Cluster compounds of gold. Gold Bull. 1975, 8, 48–52. [CrossRef] 2. Naldini, L.; Cariati, F.; Simonetta, G.; Malatesta, L. Gold-tertiary phosphine derivatives with intermetallic bonds. Chem. Commun. 1966, 647–648. [CrossRef] 3. Arratia-Pérez, R.; Hernández-Acevedo, L. Spin-orbit effects on heavy metal octahedral clusters. J. Mol. Str. THEOCHEM 1993, 282, 131–141. [CrossRef] 4. Häberlen, O.D.; Chung, S.-C.; Stener, M.; Rösch, N. From clusters to bulk: A relativistic density functional investigation on a series of gold clusters Aun, n = 6, . . . ,147. J. Chem. Phys. 1997, 106, 5189–5201. [CrossRef] 5. Deka, A.; Deka, R.C. Structural and electronic properties of stable Aun (n = 2–13) clusters: A density functional study. J. Mol. Str. THEOCHEM 2008, 870, 83–93. [CrossRef] 6. Schmidbaur, H.; Schier, A. A brieﬁng on aurophilicity. Chem. Soc. Rev. 2008, 37, 1931–1951. [CrossRef][PubMed] 2+ 7. Arratia-Perez, R.; Malli, G.L. Bonding in the octahedral Au6 cluster. Chem. Phys. Lett. 1986, 125, 143–148. [CrossRef] 2+ q+ q+ 8. Arratia-Pérez, R.; Malli, G. Dirac scattered-wave calculations for Ag 3, Au 3, and Au 4 (q = 1, 2) clusters. J. Chem. Phys. 1986, 84, 5891–5897. [CrossRef] Molecules 2021, 26, 5014 13 of 15

9. Ramos, A.F.; Arratia-Perez, R.; Malli, G.L. Dirac scattered-wave calculations on an icosahedral Au13 cluster. Phys. Rev. B 1987, 35, 3790–3798. [CrossRef][PubMed] 10. Scherbaum, F.; Grohmann, A.; Huber, B.; Krüger, C.; Schmidbaur, H. “Aurophilicity” as a Consequence of Relativistic Effects: The 2⊕ Hexakis(triphenylphosphaneaurio)methane Dication [(Ph3PAu)6C] . Angew Chem. Int. Ed. Engl. 1988, 27, 1544–1546. [CrossRef] 11. Rösch, N.; Görling, A.; Ellis, D.E.; Schmidbaur, H. Aurophilicity as concerted effect: Relativistic MO calculations on carbon- centered gold clusters. Angew Chem. Int. Ed. Engl. 1989, 28, 1357–1359. [CrossRef] 12. Morelli, F. Una Sedia d’Oro Tenuta Insieme da Due Chiodi? Identificazione di Sali di [Bis(µ3-idrosso)esacis(trifenilfosfinaoro)]. Bachelor’s Thesis, University of Sassari, Sassari, Italy, 1994. 13. Mingos, D.M. Structural and bonding patterns in gold clusters. Dalton Trans. 2015, 44, 6680–6695. [CrossRef] 14. Naldini, L.; Panzanelli, A.; Rassu, G.; Cariati, F.; Demartin, F.; Manassero, M.; Masciocchi, N. Reactions of tetrahydrogenoborate- bis(triphenylphosphine)copper(I) complex with nitrophenols. Inorg. Chim. Acta 1984, 83, L71–L73. [CrossRef] 15. Demartin, F.; Manassero, M.; Naldini, L.; Panzanelli, A.; Zoroddu, M.A. Metal complexes of 2,4-diamino-5-(30,40,50- trimethoxybenzyl)pyrimidine (trimethoprim) Part IV. Synthesis and X-ray structure of [CuCl(µ-OCH3)(trimethoprim)]2. Inorg. Chim. Acta 1990, 171, 229–233. [CrossRef] 16. Zoroddu, M.A.; Naldini, L.; Demartin, F.; Masciocchi, N. Metal complexes of 2,4-diamino-5-(30,40,50-trimethoxybenzyl)pyrimidine (trimethoprim) and 2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidine (pyrimethamine). Part III. Syntheses and x-ray structures of [Rh2(O2CCH3)4(trimethoprim)2]·2C6H6·CH3OH and [Rh2(O2CCH3)4(pyrimethamine)2]. Inorg. Chim. Acta 1987, 128, 179–183. [CrossRef] 17. Demartin, F.; Manassero, M.; Naldini, L.; Zoroddu, M.A. Metal complexes of 2,4-Diamino-5-3(30,40,50-trimethoxybenzyl)pyrimidine, (trimethoprim). Part I. Synthesis and crystal structure of CoCl2(trimethoprim)2. Inorg Chim Acta 1983, 77, L213–L214. [CrossRef] 18. Naldini, L.; Zoroddu, M.A.; Demartin, F.; Manassero, M. Synthesis and crystal structure of bis(p-amino-benzoate)2,20di- pyridylcopper(II)emiaquo. Inorg. Chim. Acta 1984, 89, L1–L2. [CrossRef] 19. Cabras, M.A.; Naldini, L.; Zoroddu, M.A.; Cariati, F.; Demartin, F.; Masciocchi, N.; Sansoni, M. Bis(triphenylphosphine)copper(I)o- and p-nitrobenzoates, synthesis and x-ray structure. Inorg. Chim. Acta 1985, 104, L19–L22. [CrossRef] 20. Crisponi, G.; Cristiani, F.; Nurchi, V.M.; Silvagni, R.; Ganadu, M.L.; Lubinu, G.; Naldini, L.; Panzanelli, A. A potentiometric, spectrophotometric and 1H NMR study on the interaction of cimetidine, famotidine and ranitidine with platinum(II) and palladium(II) metal ions. Polyhedron 1995, 14, 1517–1530. [CrossRef] 21. Bianucci, A.M.; Demartin, F.; Manassero, M.; Masciocchi, N.; Ganadu, M.L.; Naldini, L.; Panzanelli, A. Metal complexes of cimetidine. Synthesis, X-ray structure determination and semiempirical calculations on the [cimetidinatecopper(II)]+ cation. Inorg. Chim. Acta 1991, 182, 197–204. [CrossRef] 22. Naldini, L.; Demartin, F.; Manassero, M.; Sansoni, M.; Rassu, G.; Zoroddu, M.A. Synthesis and X-ray structure of [CuPPh3C≡CPh]4, an electron deficient molecule with µ-bridging phenylacetylide ligands. J. Organomet. Chem. 1985, 279, c42–c44. [CrossRef] 23. Malatesta, L.; Naldini, L.; Simonetta, G.; Cariati, F. Triphenylphosphine–gold(0)/gold(I) compounds. Chem. Commun. 1965, 1, 212–213. [CrossRef] 24. Malatesta, L.; Naldini, L.; Simonetta, G.; Cariati, F. Triphenylphosphine-gold(0)/gold(I) compounds. Coord. Chem. Rev. 1966, 1, 255–262. [CrossRef] 25. McPartlin, M.; Mason, R.; Malatesta, L. Novel cluster complexes of gold(0)–gold(I). J. Chem. Soc. D 1969, 334. [CrossRef] 26. Cariati, F.; Naldini, L.; Simonetta, G.; Malatesta, L. Clusters of gold compounds with 1,2Bis(diphenylphosphino)ethane. Inorg. Chim. Acta 1967, 1, 315–318. [CrossRef] 27. Bellon, P.L.; Cariati, F.; Manassero, M.; Naldini, L.; Sansoni, M. Novel gold clusters. Preparation, properties, and X-ray structure determination of salts of octakis(triarylphosphine)enneagold, [Au9L8]X3. J. Chem. Soc. D 1971, 1423–1424. [CrossRef] 28. Cariati, F.; Naldini, L. Preparation and properties of gold atom cluster compounds: Octakis-(triarylphosphine)enneagold trianion. J. Chem. Soc. Dalton Trans. 1972, 2286–2287. [CrossRef] 29. Adnan, R.H.; Andersson, G.G.; Polson, M.I.J.; Metha, G.F.; Golovko, V.B. Factors influencing the catalytic oxidation of benzyl alcohol using supported phosphine-capped gold nanoparticles. Catal. Sci. Technol. 2015, 5, 1323–1333. [CrossRef] 30. Manassero, M.; Naldini, L.; Sansoni, M. A new class of gold cluster compounds. Synthesis and X-ray structure of the octakis(triphenylphosphinegold) dializarinsulphonate, [Au8(PPh3)8](aliz)2. J. Chem. Soc. Chem. Commun. 1979, 385–386. [CrossRef] 31. Wen, F.; Englert, U.; Gutrath, B.; Simon, U. Crystal structure, electrochemical and optical properties of [Au9(PPh3)8](NO3)3. Eur. J. Inorg. Chem. 2008, 2008, 106–111. [CrossRef] 32. Demartin, F.; Manassero, M.; Naldini, L.; Ruggeri, R.; Sansoni, M. Synthesis and X-ray characterization of an iodine-bridged tetranuclear gold cluster, di-µ-iodo-tetrakis(triphenylphosphine)-tetrahedro-tetragold. J. Chem. Soc. Chem. Commun. 1981, 222–223. [CrossRef] 33. Bruce, M.I.; Duffy, D.N. Chemistry of the group-1B metals. XVIII. Crystal and molecular structures of nitratotris(triphenylphosphine) silver(I), Ag(O2NO)(PPh3)3. Aust. J. Chem. 1986, 39, 1691–1695. [CrossRef] 34. Ganadu, M.L.; Naldini, L.; Crisponi, G.; Nurchi, V. 1H and 13C NMR studies of (phenylethynyl) (triphenylphosphine) gold(I). Spectrochim. Acta A Mol. Biomol. Spectrosc. 1991, 47, 615–621. [CrossRef] 35. Demartin, F.; Ganadu, M.L.; Lubinu, G.; Naldini, L.; Panzanelli, A. Synthesis, NMR study, and X-ray structure of 2-(N-methyl-N0- cyano-N”-ethylguanidino) thiotriophenylphosphinegold(I). J. Inorg. Biochem. 1995, 60, 233–243. [CrossRef] Molecules 2021, 26, 5014 14 of 15

36. Yang, Y.; Ramamoorthy, V.; Sharp, P.R. Late transition metal oxo and imido complexes. 11. Gold(I) oxo complexes. Inorg. Chem. 1993, 32, 1946–1950. [CrossRef] 37. Briant, C.E.; Hall, K.P.; Mingos, D.M.P. Synthesis and structural characterisation of [Au6(PPh3)6]- (NO3)2·3CH2Cl2; an edge-shared bitetrahedral gold cluster. J. Organomet. Chem. 1983, 254, C18–C20. [CrossRef] 38. Ramamoorthy, V.; Wu, Z.; Yi, Y.; Sharp, P.R. Preparation and decomposition of gold(I) hydrazido complexes: Gold cluster formation. J. Am. Chem. Soc. 1992, 114, 1526–1527. [CrossRef] 39. Van der Velden, J.W.A.; Bour, J.J.; Steggerda, J.J.; Beurskens, P.T.; Roseboom, M.; Noordik, J.H. Gold clusters. Tetrakis[1,3- bis(diphenylphosphino)propane]hexagold dinitrate: Preparation, x-ray analysis, and gold-197 Moessbauer and phosphorus- 31{proton} NMR spectra. Inorg. Chem. 1982, 21, 4321–4324. [CrossRef] 2+ 40. Angermaier, K.; Schmidbaur, H. A new structural motif of gold clustering at oxide centers in the dication [Au6O2(PMe3)6] . Inorg. Chem. 1994, 33, 2069–2070. [CrossRef] 41. Hong, X.; Cheung, K.-K.; Guo, C.-X.; Che, C.-M. Luminescent organometallic gold(I) complexes. Structure and photophysical properties of alkyl-, aryl- and µ-ethynylene gold(I) complexes. J. Chem. Soc. Dalton Trans. 1994, 1867–1871. [CrossRef] 42. Battistoni, C.; Mattogno, G.; Zanoni, R.; Naldini, L. Characterisation of some gold clusters by X-ray photoelectron spectroscopy. J. Electron. Spectros. Relat. Phenom. 1982, 28, 23–31. [CrossRef] 43. Nagashima, E.; Yoshida, T.; Matsunaga, S.; Nomiya, K. The effect of counteranions on the molecular structures of phosphanegold(I) cluster cations formed by polyoxometalate (POM)-mediated clusterization. Dalton Trans. 2016, 45, 13565–13575. [CrossRef] [PubMed] 44. Qu, X.; Li, Y.; Li, L.; Wang, Y.; Liang, J.; Liang, J. Fluorescent gold nanoclusters: Synthesis and recent biological application. J. Nanomat. 2015, 2015, 784097. [CrossRef] 45. Kang, X.; Zhu, M. Tailoring the photoluminescence of atomically precise nanoclusters. Chem. Soc. Rev. 2019, 48, 2422–2457. [CrossRef][PubMed] 46. Nonappa, N. Luminescent gold nanoclusters for bioimaging applications. Beilstein J. Nanotechnol. 2020, 11, 533–546. [CrossRef] 47. Liu, M.; Tang, F.; Yang, Z.; Xu, J.; Yang, X. Recent progress on gold-nanocluster-based fluorescent probe for environmental analysis and biological sensing. J. Anal. Methods Chem. 2019, 2019, 1095148. [CrossRef][PubMed] 48. Zeng, C.; Jin, R. Chiral gold nanoclusters: Atomic level origins of chirality. Chem. Asian J. 2017, 12, 1839–1850. [CrossRef] 49. Agrachev, M.; Antonello, S.; Dainese, T.; Ruzzi, M.; Zoleo, A.; Apra, E.; Govind, N.; Fortunelli, A.; Sementa, L.; Maran, F. Magnetic ordering in gold nanoclusters. ACS Omega 2017, 2, 2607–2617. [CrossRef][PubMed] 50. Häkkinen, H. Atomic and electronic structure of gold clusters: Understanding flakes, cages and superatoms from simple concepts. Chem. Soc. Rev. 2008, 37, 1847–1859. [CrossRef] 51. Raubenheimer, H.G.; Schmidbaur, H. Gold chemistry guided by the isolobality concept†. Organometallics 2012, 31, 2507–2522. [CrossRef] 52. Tian, Z.; Liu, W.; Cheng, L. Progress of the experimental and theoretical studies on Aum(SR)n clusters. Prog. Chem. 2015, 27, 1743. 53. Du, Y.; Sheng, H.; Astruc, D.; Zhu, M. Atomically precise noble metal nanoclusters as efficient catalysts: A bridge between structure and properties. Chem. Rev. 2020, 120, 526–622. [CrossRef] 54. Zhang, B.; Chen, J.; Cao, Y.; Chai, O.J.H.; Xie, J. Ligand design in ligand-protected gold nanoclusters. Small 2021, e2004381. [CrossRef] 55. Sousa, L.M.; Vilarinho, L.M.; Ribeiro, G.H.; Bogado, A.L.; Dinelli, L.R. An electronic device based on gold nanoparticles and tetraruthenated porphyrin as an electrochemical sensor for catechol. R. Soc. Open Sci. 2017, 4, 170675. [CrossRef][PubMed] 56. Diao, J.J.; Cao, Q. Gold nanoparticle wire and integrated wire array for electronic detection of chemical and biological molecules. AIP Adv. 2011, 1, 012115. [CrossRef] 57. Hutchings, G.J.; Edwards, J.K. Chapter 6—Application of gold nanoparticles in catalysis. In Frontiers of Nanoscience; Johnston, R.L., Wilcoxon, J.P., Eds.; Elsevier: Amsterdam, The Netherlands, 2012; Volume 3, pp. 249–293. 58. Astruc, D. Introduction: Nanoparticles in catalysis. Chem. Rev. 2020, 120, 461–463. [CrossRef] 59. Thompson, D.T. Using gold nanoparticles for catalysis. Nano Today 2007, 2, 40–43. [CrossRef] 60. Chhour, P.; Naha, P.C.; Cheheltani, R.; Benardo, B.; Mian, S.; Cormode, D.P. Gold nanoparticles for biomedical applications: Synthesis and in vitro evaluation. In Nanomaterials in Pharmacology; Lu, Z.-R., Sakuma, S., Eds.; Springer: New York, NY, USA, 2016; pp. 87–111. 61. Cabuzu, D.; Cirja, A.; Puiu, R.; Grumezescu, M.A. Biomedical applications of gold nanoparticles. Curr. Top. Med. Chem. 2015, 15, 1605–1613. [CrossRef][PubMed] 62. Elahi, N.; Kamali, M.; Baghersad, M.H. Recent biomedical applications of gold nanoparticles: A review. Talanta 2018, 184, 537–556. [CrossRef][PubMed] 63. Dykman, L.; Khlebtsov, N. Gold Nanoparticles in Biomedical Applications, 1st ed.; CRC Press: New York, NY, USA, 2017. 64. Medici, S.; Peana, M.; Coradduzza, D.; Zoroddu, M.A. Gold nanoparticles and cancer: Detection, diagnosis and therapy. Semin. Cancer Biol. 2021.[CrossRef] 65. Wu, Z.; Yao, Q.; Chai, O.J.H.; Ding, N.; Xu, W.; Zang, S.; Xie, J. Unraveling the impact of gold(I)–thiolate motifs on the aggregation-induced emission of gold nanoclusters. Angew Chem. Int. Ed. Engl. 2020, 59, 9934–9939. [CrossRef] 66. Wang, E.; Xu, W.W.; Zhu, B.; Gao, Y. Understanding the chemical insights of staple motifs of thiolate-protected gold nanoclusters. Small 2021, 17, 2001836. [CrossRef][PubMed] Molecules 2021, 26, 5014 15 of 15

67. Walter, M.; Akola, J.; Lopez-Acevedo, O.; Jadzinsky, P.D.; Calero, G.; Ackerson, C.J.; Whetten, R.L.; Grönbeck, H.; Häkkinen, H. A unified view of ligand-protected gold clusters as superatom complexes. Proc. Natl. Acad. Sci. USA 2008, 105, 9157. [CrossRef] 68. Pyykkö, P. Understanding the eighteen-electron rule. J. Organomet. Chem. 2006, 691, 4336–4340. [CrossRef] 69. Hirai, H.; Takano, S.; Nakamura, T.; Tsukuda, T. Understanding doping effects on electronic structures of gold superatoms: A case study of diphosphine-protected M@Au12 (M = Au, Pt, Ir). Inorg. Chem. 2020, 59, 17889–17895. [CrossRef][PubMed] 70. De Heer, W.A. The physics of simple metal clusters: Experimental aspects and simple models. Rev. Mod. Phys. 1993, 65, 611–676. [CrossRef] 71. Narouz, M.R.; Takano, S.; Lummis, P.A.; Levchenko, T.I.; Nazemi, A.; Kaappa, S.; Malola, S.; Yousefalizadeh, G.; Calhoun, L.A.; Stamplecoskie, K.G.; et al. Robust, highly luminescent Au13 superatoms protected by N-heterocyclic carbenes. J. Am. Chem. Soc. 2019, 141, 14997–15002. [CrossRef] (2+) 72. Takano, S.; Hirai, H.; Muramatsu, S.; Tsukuda, T. Hydride-doped gold superatom (Au9H) : Synthesis, structure, and transformation. J. Am. Chem. Soc. 2018, 140, 8380–8383. [CrossRef] 73. Maman, M.P.; Nair, A.S.; Cheraparambil, H.; Pathak, B.; Mandal, S. Size Evolution dynamics of gold nanoclusters at an atom- precision level: Ligand exchange, growth mechanism, electrochemical, and photophysical properties. J. Phys. Chem. Lett. 2020, 11, 1781–1788. [CrossRef] 74. Liao, L.; Zhuang, S.; Yao, C.; Yan, N.; Chen, J.; Wang, C.; Xia, N.; Liu, X.; Li, M.B.; Li, L.; et al. Structure of chiral Au44(2,4-DMBT)26 nanocluster with an 18-electron shell closure. J. Am. Chem. Soc. 2016, 138, 10425–10428. [CrossRef] 75. Chakraborty, I.; Pradeep, T. Atomically precise clusters of noble metals: Emerging link between atoms and nanoparticles. Chem. Rev. 2017, 117, 8208–8271. [CrossRef][PubMed] 76. Knoppe, S.; Bürgi, T. Chirality in thiolate-protected gold clusters. Acc. Chem. Res. 2014, 47, 1318–1326. [CrossRef][PubMed] 77. Pelayo, J.J.; Whetten, R.L.; Garzón, I.L. Geometric quantification of chirality in ligand-protected metal clusters. J. Phys. Chem. C 2015, 119, 28666–28678. [CrossRef] 78. Wan, X.K.; Yuan, S.F.; Lin, Z.W.; Wang, Q.M. A chiral gold nanocluster Au20 protected by tetradentate phosphine ligands. Angew Chem. Int. Ed. Engl. 2014, 53, 2923–2926. [CrossRef][PubMed] 79. Sugiuchi, M.; Shichibu, Y.; Konishi, K. An inherently chiral Au24 framework with double-helical hexagold strands. Angew Chem. Int. Ed. Engl. 2018, 57, 7855–7859. [CrossRef][PubMed] 80. Wang, J.Q.; Guan, Z.J.; Liu, W.D.; Yang, Y.; Wang, Q.M. Chiroptical activity enhancement via structural control: The chiral synthesis and reversible interconversion of two intrinsically chiral gold nanoclusters. J. Am. Chem. Soc. 2019, 141, 2384–2390. [CrossRef][PubMed] 81. Dau, T.M.; Chen, Y.A.; Karttunen, A.J.; Grachova, E.V.; Tunik, S.P.; Lin, K.T.; Hung, W.Y.; Chou, P.T.; Pakkanen, T.A.; Koshevoy, I.O. Tetragold(I) complexes: Solution isomerization and tunable solid-state luminescence. Inorg. Chem. 2014, 53, 12720–12731. [CrossRef] 82. Hau, F.K.; Lee, T.K.; Cheng, E.C.; Au, V.K.; Yam, V.W. Luminescence color switching of supramolecular assemblies of discrete molecular decanuclear gold(I) sulfido complexes. Proc. Natl. Acad. Sci. USA 2014, 111, 15900–15905. [CrossRef] 83. Ge, S.; Zhao, J.; Ma, G. Thiol stabilized extremely small gold cluster complexes with high photoluminescence. Inorg. Chem. Comm. 2019, 109, 107556. [CrossRef] 84. Liu, C.Y.; Wei, X.R.; Chen, Y.; Wang, H.F.; Ge, J.F.; Xu, Y.J.; Ren, Z.G.; Braunstein, P.; Lang, J.P. Tetradecanuclear and octadecanuclear Gold(I) sulfido clusters: Synthesis, structures, and luminescent selective tracking of lysosomes in living cells. Inorg. Chem. 2019, 58, 3690–3697. [CrossRef] 85. Xu, W.W.; Zhu, B.; Zeng, X.C.; Gao, Y. A grand unified model for liganded gold clusters. Nat. Commun. 2016, 7, 13574. [CrossRef] [PubMed] 2+ 86. Karimova, N.V.; Aikens, C.M. Optical properties of small gold clusters Au8L8 (L = PH3, PPh3): Magnetic circular dichroism spectra. J. Phys. Chem. C 2017, 121, 19478–19489. [CrossRef] 87. McKenzie, L.C.; Zaikova, T.O.; Hutchison, J.E. Structurally similar triphenylphosphine-stabilized undecagolds, Au11(PPh3)7Cl3 and [Au11(PPh3)8Cl2]Cl, exhibit distinct ligand exchange pathways with glutathione. J. Am. Chem. Soc. 2014, 136, 13426–13435. [CrossRef][PubMed] 88. Konishi, K. Phosphine-coordinated pure-gold clusters: Diverse geometrical structures and unique optical properties/responses. In Gold Clusters, Colloids and Nanoparticles I; Mingos, D.M.P., Ed.; Springer International Publishing: Cham, Switzerland, 2014; pp. 49–86. 89. Reddy, S.T.; Priver, S.H.; Rao, V.V.; Mirzadeh, N.; Bhargava, S.K. Gold(I) and gold(III) phosphine complexes: Synthesis, anticancer activities towards 2D and 3D cancer models, and apoptosis inducing properties. Dalton Trans. 2018, 47, 15312–15323. [CrossRef] [PubMed]