crystals

Article Water Structures and Packing Efficiency in Methylene Blue Cyanometallate Salts

Stefano Canossa 1,* , Claudia Graiff 2,* , Domenico Crocco 2 and Giovanni Predieri 2

1 EMAT, Department of Physics, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium 2 Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale, Università degli Studi di Parma, Via Parco Area delle Scienze 17/A, 43124 Parma, Italy; [email protected] (D.C.); [email protected] (G.P.) * Correspondence: [email protected] (S.C.); claudia.graiff@unipr.it (C.G.)



Received: 26 May 2020; Accepted: 5 June 2020; Published: 1 July 2020


Abstract: Crystal structure prediction is the holy grail of crystal engineering and is key to its ambition of driving the formation of solids based on the selection of their molecular constituents. However, this noble quest is hampered by the limited predictability of the incorporation of solvent molecules, first and foremost the ubiquitous water. In this context, we herein report the structure of four methylene blue cyanometallate phases, where anions with various shapes and charges influence the packing motif and lead to the formation of differently hydrated structures. Importantly, water molecules are observed to play various roles as isolated fillings, dimers, or an infinite network with up to 13 water molecules per repeating unit. Each crystal structure has been determined by single-crystal X-ray diffraction and evaluated with the aid of Hirshfeld surface analysis, focussing on the role of water molecules and the hierarchy of different classes of interactions in the overall supramolecular landscape of the crystals. Finally, the collected pieces of evidence are matched together to highlight the leading role of MB stacking and to derive an explanation for the observed hydration diversity based on the structural role of water molecules in the crystal architecture.

Keywords: methylene blue; water structure; hydrogen bond; crystal packing

1. Introduction Methylene blue (MB) is a widely known compound whose redox and optical properties have been studied and employed for decades in chemistry [1,2], medicine [3–6], and biology [7,8]. Commonly commercialised as a chloride salt, MB owes its most relevant properties to the cationic heteroaromatic + + compound 3,7-bis(dimethylamino)-phenothiazin-5-ium (MB ; chemical formula C16H18SN3 as shown in Figure1a), which is responsible for the intense blue colour of its aqueous solutions. As far as its solid-state behaviour is concerned, two interactions play a dominant role: the aromatic π-π stacking between MB+ and its same neighbours, and the electrostatic and hydrogen bond interactions involving the lone pair of its aromatic nitrogen. This last propensity is determined by the peculiar molecular electronic structure of MB+ and particularly by the presence of an exposed σ lone pair on this nitrogen, as discussed in our previous study [9]. Both these interaction tendencies are recognizable in the interaction probability map of the isolated cation, shown in Figure1b [ 10]. While on the one hand the importance of aromatic stacking in the crystal packing of MB+ is supported by its occurrence in all the structures reported up until now [11,12], on the other hand various stacking modes have been reported depending on the anionic counterpart and the presence of other species, especially solvents, participating in the crystal architecture [13]. In this regard, methylene blue salts have shown a strong tendency to incorporate water molecules in their periodic structures, not rarely with various possible stoichiometries for a single type of counter-anion.

Crystals 2020, 10, 558; doi:10.3390/cryst10070558 www.mdpi.com/journal/crystals Crystals 2020, 10, x FOR PEER REVIEW 2 of 12 Crystals 2020, 10, 558 2 of 12

Perhaps the most representative example is the pseudo-polymorphism of methylene blue hydrates,Perhaps of which the most up representative to five distinct example forms iswith the pseudo-polymorphismdifferent amounts of structural of methylene water blue molecules hydrates, haveof which been up reported to five [14]. distinct In particular, forms with the di occurrefferent amountsnce of such of hydration structural polymorphism water molecules is haveknown been to complicatereported [14 crystal]. In particular, structure theprediction occurrence and ofsynthesis such hydration of molecular polymorphism solids to the is knownpoint that to complicatewater has beencrystal regarded structure to prediction as the “nemesis and synthesis of crystal of molecularengineering” solids [15]. to theThis point makes that systematic water has studies been regarded on the roleto as of the water “nemesis in the of crystal crystal packing engineering” of molecular [15]. This materials makes systematicparticularly studies valuable on the and role functional of water to in the the definitioncrystal packing of strategies of molecular to identify materials the particularly main aspects valuable ruling and the functional formation to theof water-based definition of strategiespseudo- polymorphism.to identify the main Aiming aspects to conduct ruling thesuch formation investigation of water-based on the crystallisation pseudo-polymorphism. processes of methylene Aiming to blueconduct salts, such we investigationsynthesized a on series the crystallisationof four methylene processes blue cyanometallate of methylene blue phases salts, using we synthesized anions with a differentseries of fourcharges methylene and geometries, blue cyanometallate and in the phases presen usingce of anions water with traces diff erentin the charges crystallisation and geometries, media (non-anhydrousand in the presence organic of water solvents). traces The in the choice crystallisation of this class media of (non-anhydrousmetal complexes organic allowed solvents). us to selectivelyThe choice vary of this the class geometric of metal and complexes charge features allowed of the us toanionic selectively moieties, vary while the geometric maintaining and the charge type offeatures chemical of thegroups anionic that moieties, they cont whileribute maintaining with to the overall the type supramol of chemicalecular groups network. that For they each contribute phase, thewith overall to the overall packing supramolecular features are network. scrutinised For eachto understand phase, the overall how packingwater molecules features are fit scrutinised into the interactionsto understand landscape, how water and molecules finally identify fit into the the interactions primary reasons landscape, for andtheir finally presence identify and thesolid-state primary interactions.reasons for their presence and solid-state interactions.

FigureFigure 1. Resonant structures ofof MBMB++ ((aa)) andand its its interaction interaction probability probability map map (b )(b calculated) calculated by by using using the the“Full “Full Interaction Interaction Map” Map” tool oftool the of software the software Mercury Me [rcury10]. As [10]. in allAs the in otherall the figures, other thefigures, light the elements light elementscolour code colour is: C code= grey; is: C O == grey;red; O S == yellow;red; S = Nyellow;= blue; N H= blue;= white. H = white. .

2.2. Materials Materials and and Methods Methods

2.1. General Remarks 2.1. General Remarks All solid and liquid reagents have been purchased by commercial sources and used without All solid and liquid reagents have been purchased by commercial sources and used without further purification. Crystallisations by slow solvent evaporation were conducted at room temperature further purification. Crystallisations by slow solvent evaporation were conducted at room and pressure, and in the presence of air and atmospheric moisture. temperature and pressure, and in the presence of air and atmospheric moisture. 2.2. Synthetic Procedures 2.2. Synthetic Procedures

2.2.1. Synthesis of MB2[Ni(CN)4] 2H2O 2.2.1. Synthesis of MB2[Ni(CN)4]·2H· 2O Fifty-one milligrams of methylene blue pentahydrate (0.159 mmol) and 19 mg of K2Ni(CN)4 (0.079Fifty-one mmol) weremilligrams transferred of methylene into a 25 mLblue glass pentahydrate vial. Twenty (0.159 millilitres mmol) of and N,N-dimethylformamide 19 mg of K2Ni(CN)4 (0.079was added mmol) to were the powder transferred mixture into a and 25 mL the vialglass was vial. closed Twenty with millilitres a screw of cap N,N-dimethylformamide and transferred into an wasultrasound added to bath the to powder be sonicated mixture for and 5 min. the The vial resulting was closed clear with blue a solutionscrew cap was and left transferred to evaporate into in an an ultrasoundopen 50 mL bath crystallisation to be sonicated dish. Afterfor 5 min. 7 days The of slowresulting solvent clear evaporation, blue solution dark was metallic-green left to evaporate needles in anwere open found 50 mL in solution, crystallisation and were dish. subsequently After 7 days isolated of slow for solvent single-crystal evaporation, X-ray analysis.dark metallic-green needles were found in solution, and were subsequently isolated for single-crystal X-ray analysis. 2.2.2. Synthesis of MB2[Fe(CN)5NO] 2.2.2. Synthesis of MB2[Fe(CN)5NO] Ten milligrams of methylene blue pentahydrate (0.03 mmol) and 5 mg of Na2[Fe(CN)5NO] (0.015Ten mmol) milligrams were of transferred methylene into blue a pent 25 mLahydrate glass (0.03 vial, mmol) and 20 and mL 5 of mg a of H 2NaO-acetone2[Fe(CN)5 mixtureNO] (0.015 1:1 mmol)was added were to transferred the powder into mixture a 25 mL and glass the vial, vial wasand closed20 mL withof a H a2O-acetone screw cap andmixture transferred 1:1 was intoadded an toultrasound the powder bath mixture to be sonicated and the vial for 5was min. closed The thuswith obtained a screw clearcap and blue transferred solution was into left an to ultrasound evaporate bath to be sonicated for 5 min. The thus obtained clear blue solution was left to evaporate in a 50 mL

Crystals 2020, 10, 558 3 of 12 in a 50 mL crystallisation dish. After 20 days of slow evaporation, golden needle-shaped crystals were found and subsequently collected for single-crystal X-ray analysis.

2.2.3. Synthesis of MB [Fe(CN) ] H O and MB [Fe(CN) ] 12.36H O 3 6 · 2 3 6 · 2 Twenty milligrams of methylene blue pentahydrate (0.06 mmol) and 7 mg of K3Fe(CN)6 (0.02 mmol) were transferred into a 25 mL glass vial. Then, 20 mL of N,N-dimethylformamide was added to the powder mixture and the vial was closed with a screw cap and transferred into an ultrasound bath to be sonicated for 5 min. The resulting clear blue solution was left to evaporate in an open 50 mL crystallisation dish. After 6 days of slow solvent evaporation, two crystalline phases were observed present in the mother liquor: golden needles and metallic dark-green prisms. Both crystal phases were isolated for single-crystal X-ray analysis.

2.3. Single-Crystal X-ray Diffraction Analysis Crystallographic analyses on single crystal specimens of MB [Fe(CN) NO], MB [Fe(CN) ] H O 2 5 3 6 · 2 and MB [Fe(CN) ] 12.36H O were carried out at the XRD1 beamline at the Elettra synchrotron (CNR 3 6 · 2 Trieste) [16]. Diffraction data were collected at 100K using a monochromatic 0.7 Å wavelength (17.712 keV), using a cold nitrogen stream produced with an Oxford Cryostream 700 (Oxford Cryosystems Ltd., Oxford, UK). Diffraction images were recorded on a Pilatus 2M detector. Diffraction data on MB [Ni(CN) ] 2H O were collected on a SMART APEX2 diffractometer using graphite 2 4 · 2 monochromated Mo Kα radiation (λ = 0.71073 Å) and an APEX II CCD detector. Synchrotron datasets were processed using the software package Rigaku CrysAlisPro ver. 1.171.40.67a [17]. Empirical absorption correction was performed by the SCALE3 ABSPACK program ver. 1.0.11 included in the CrysAlisPro software suite. Diffraction data of MB [Ni(CN) ] 2H O were 2 4 · 2 processed using the software Bruker Apex3 [18], performing an empirical “multi-scan” absorption correction. All the structure determinations were conducted using Olex2 software ver. 1.3.0 [19], using the programs ShelXT and ShelXL for structure solution and least square refinement of the atomic coordinates, respectively. All non-hydrogen atoms were refined anisotropically. Suitable restraints assisted the anisotropic refinement of atoms belonging to disordered molecules. All hydrogen atoms were located upon examination of residual electron densities in the difference Fourier maps and therefore placed and fixed in idealized positions. Further details of data reduction, crystallographic refinements for each sample and reciprocal space sections of the disordered phases MB2[Fe(CN)5NO] and MB [Fe(CN) ] H O are provided in the supplementary materials. 3 6 · 2 The structures reported in this work can be accessed free of charge from the Cambridge Structural Database website (https://www.ccdc.cam.ac.uk/structures/); deposition numbers 2004494–2004497.

2.4. Computational Details Hirshfeld surface calculation functional to the creation of Hirshfeld plots used in the discussion was conducted by using the software Crystal Explorer version 17.05 [20]. Each species was set to singlet state, and molecular charges were adjusted prior to the calculation. This was performed using the default settings (surface: “Hirshfeld”, property: “none”) and “very high” resolution settings. Atomic packing factors (APFs) were calculated as APF = 1 V /V . The V parameters were − void cell void derived by using the “Display Void” function of the software “Mercury” of the Cambridge Structural Database System [11]. For this calculation, the “contact surface” method was used with a probe radius of 0.2 Å and a grid spacing of 0.1 Å. Disordered structures have been considered in only one of their equivalent configurations. Their crystallographic symmetry was reduced to the pure translational symmetry (P1 settings) by using the software Vesta [21] and the excess atoms were removed by the model, resulting in a chemically sound structure, which was used for the APF calculations. Crystals 2020, 10, 558 4 of 12

3.Crystals Results 2020 and, 10, x Discussion FOR PEER REVIEW 4 of 12

3.1. SystematicThe effect Variation of both charge of Cyanometallate and geometry Ions of the anions were probed by employing three different species:The etheffect square of both planar charge tetracyanonickelate(II) and geometry of the [Ni(CN) anions were4]2−, the probed octahedral by employing nitroprusside three 2− 3− 2 di[Fe(CN)fferent5 species:(NO)] theand square the octahedral planar tetracyanonickelate(II) ferricyanide [Fe(CN) [Ni(CN)6] . Given4] − ,the the isoelectronic octahedral nitroprusside character of 2 3 [Fe(CN)cyanide5 (NO)]and nitrosyl− and thegroups octahedral and therefore ferricyanide of th [Fe(CN)e two iron6] − .anions, Given thetheir isoelectronic use combined character with the of cyanidedivalent and nickel nitrosyl species groups allows and therefore us to test of the the two effects iron anions, of different their use charge combined ([Fe(CN) with the5(NO)] divalent2− vs. 3− 2− 2− 2 2−3 nickel[Fe(CN) species6] ), different allows usgeometry to test the([Ni(CN) effects4] of vs. di ff[Fe(CN)erent charge5(NO)] ([Fe(CN)) or both5(NO)] combined− vs. ([Ni(CN) [Fe(CN)46]] −vs.), 3− 2 2 2 3 di[Fe(CN)fferent geometry6] ). By using ([Ni(CN) these4 ]anions,− vs. [Fe(CN) four products5(NO)] − were) or both obtained combined as the ([Ni(CN) use of 4ferricyanide] − vs. [Fe(CN) resulted6] −). Byin usingtwo distinct these anions,phases fourwith productssignificantly were different obtained wa aster the content. use of ferricyanideInterestingly, resulted all four inproducts two distinct show phasesa unique with crystal significantly packing di situationfferent water not only content. concerning Interestingly, methylene all four blue products cations’ show stacking a unique and crystaloverall packingdegree of situation solvation, not onlybut also concerning with respect methylene to stru bluectural cations’ disorder. stacking These and aspects overall are degree described of solvation, below butfor alsoeachwith product. respect A todetailed structural description disorder. of Thesethe crystallographic aspects are described modelling below can for be eachfound product. in the Asupplementary detailed description materials. of the crystallographic modelling can be found in the supplementary materials.

3.2.3.2. CrystalCrystal StructureStructure AnalysisAnalysis

TheThe structure structure of of MB MB2[Ni(CN)[Ni(CN)4]]·2H2H 2OO (1) features MBMB cationscations performingperforming infiniteinfinite zig-zagzig-zag stackingstacking 2 4 · 2 columnscolumns separatedseparated byby verticallyvertically alignedaligned anions,anions, andand connectedconnected byby water-basedwater-based hydrogenhydrogen bondsbonds (Figure(Figure2 ).2). The The mutual mutual orientation orientation of of the the MB MB cations cations in in the the stacking stacking columns columns consists consists of of two two types, types, whichwhich we we define define as as opposite opposite (O) (O) or or same same (S), (S), and and alternates alternates forming forming dimers dimers of of same-orientation same-orientation MB MB++ (Figure(Figure2 a,b).2a,b). The The resulting resulting sequence sequence along along the the stacking stacking direction direction is “ is... “…O–S–O–S…”,O–S–O–S ... ”, as cancan bebe observedobserved in in Figure Figure2b. 2b. The The presence presence of oneof one water water molecule molecule for eachfor each MB MB ensures ensures the stabilisationthe stabilisation of the of aromaticthe aromatic nitrogen nitrogen lone lone pair viapair hydrogen via hydrogen bonding bonding (Figure (Figure2c; distances: 2c; distances: 2.197(16) 2.197(16) Å for Å H forN1 H···N1 and ··· 2.224(15)and 2.224(15) Å for Å H forN2). H···N2). Additional Additional hydrogen hydrogen bonds bonds with with the methylthe methyl groups groups from from MB MB belonging belonging to ··· ditoff erentdifferent columns columns and and with with cyanonickelate cyanonickelate ions ions allow allow every every pair ofpair water of water molecules molecules to connect to connect three distinctthree distinct MB+ columns MB+ columns and one and anion. one anion. It is worthIt is worth highlighting highlighting that thethat stacking the stacking columns columns share share the samethe same alignment alignment of MB of MB molecules, molecules, which which lie lie with with their their longer longer dimension dimension along along the the [1 [1 0 0 0] 0] direction.direction. TheThe flat flat cyanonickelate cyanonickelate ions ions also also show show this this orientation. orientation. AlthoughAlthough thethe rolerole ofof thethe solventsolvent inin stabilisingstabilising thethe observedobserved configurationconfiguration shouldshould notnot bebe underestimated, underestimated, thethe describeddescribed packingpacking preferencepreference mightmight bebe stronglystrongly promoted promoted by by the the presence presence of of flat flat anions, anions, which which can can act act as as spacers spacers between between MB MB++columns columns withoutwithout hindering hindering their their formation. formation.

Figure 2. Crystal packing of 1 viewed along the [0 0 1] and [1 0 0] crystal directions (part “a” and “b” Figure 2. Crystal packing of 1 viewed along the [0 0 1] and [1 0 0] crystal directions (part “a” and “b” respectively). The hydrogen bonding network allowed by the water molecules is shown in part “c”. respectively). The hydrogen bonding network allowed by the water molecules is shown in part “c”.

In MB2[Fe(CN)5NO] (2), the system copes with a substantially different dimensionality of the anion.In As MB a2 result,[Fe(CN) MB5NO]+ columns (2), the aresystem not alignedcopes with in a a common substantially direction, different but lie dimensionality orthogonal to of each the + other,anion. creating As a result, square MB channels columns bordered are not with aligned methyl in groups.a common Here, direction, the anions but are lie piled orthogonal up and to accept each hydrogenother, creating bonds square from the channels methyl groupsbordered onto with every methyl cyanide groups./nitrosyl Here, ligand the (Figure anions3 a).are As piled every up MB and+ contributesaccept hydrogen to four bonds different from “anionic” the methyl channels groups and on alongto every the stackingcyanide/nitrosyl direction ligand the length (Figure covered 3a). byAs + oneevery anion MB corresponds contributes to four that ofdifferent a MB+ “anionic”dimer, the channe cationsls adopt and along an “opposite” the stacking stacking direction type the to length yield + acovered more favourable by one anion hydrogen-bonding corresponds to that coverage of a MB for thedimer, anions the (Figurecations3 adoptb). These an “opposite” latter anions stacking lie in type to yield a more favourable hydrogen-bonding coverage for the anions (Figure 3b). These latter sites having Ci symmetry and show positional disorder where the nitrosyl ligand is alternative to the anions lie in sites having Ci symmetry and show positional disorder where the nitrosyl ligand is alternative to the cyanide groups in four coplanar positions. Importantly, no water molecules participate in the crystal, and the closest hydrogen bond donor for the MB aromatic nitrogen is a

Crystals 2020, 10, 558 5 of 12 Crystals 2020, 10, x FOR PEER REVIEW 5 of 12 cyanideCrystals 2020 groups, 10, x FOR in four PEER coplanar REVIEW positions. Importantly, no water molecules participate in the crystal,5 of 12 methyl group belonging to an adjacent column, although the CH···N distance of 2.871(2) Å highlights and the closest hydrogen bond donor for the MB aromatic nitrogen is a methyl group belonging to its rather weak character (Figure 3c). anmethyl adjacent group column, belonging although to an theadjacent CH column,N distance although of 2.871(2) the CH···N Å highlights distance its of rather 2.871(2) weak Å highlights character ··· (Figureits rather3c). weak character (Figure 3c).

Figure 3. Crystal packing of 2 viewed along the [1 0 0] and [−1 1 1] crystal directions (part “a” and “b” Figure 3. Crystal packing of 2 viewed along the [1 0 0] and [ 1 1 1] crystal directions (part “a” and “b” respectively). In “c”, the chemical environment of MB+ in the asymmetric unit is displayed without Figure 3. Crystal packing of 2 viewed along the [1 0 0] +and [−−1 1 1] crystal directions (part “a” and “b” respectively). In+ “c”, the chemical environment of MB in the asymmetric unit is displayed without showing the MB stacked below and above and by showing+ the anion in white for the sake of clarity. showingrespectively). the MB In+ “stackedc”, the chemical below and environment above and byof showingMB in the the asymmetric anion in white unit for is thedisplayed sake of without clarity. showing the MB+ stacked below and above and by showing the anion in white for the sake of clarity. A similar arrangement is found in MB3[Fe(CN)6]·H2O (3), where likewise stacked MB columns A similar arrangement is found in MB3[Fe(CN)6] H2O (3), where likewise stacked MB columns create square channels to allocate ferricyanide anions (Figure· 4a). However, in this case, the trivalent createA square similar channels arrangement to allocate is found ferricyanide in MB3[Fe(CN) anions6 (Figure]·H2O (3),4a). where However, likewise in this stacked case, theMB trivalent columns anionanioncreate issquare distributed channels differently diff toerently allocate along ferricyanide the channel channel anions due due (Figureto to the the charge charge4a). Ho requirements. requirements.wever, in this Incase, In fact, fact, the while whiletrivalent in in 2 2eachanion each MB is MB distributedpair pair is issurrounded surrounded differently by by fouralong four anions the anions channel and and each eachdue anion to anion the is embracedcharge is embraced requirements. by byfour four MB MB Inpairs—hence fact, pairs—hence while inthe 2 thechargeeach charge MB balance—in pair balance—in is surrounded the case the case ofby 3four, ofthe 3, anions distribution the distribution and each of theanion of anion the is embraced anion along along the by channels thefour channels MB is pairs—hence such is that such every that the + everyanioncharge anionin balance—in embraced in embraced by the four case by MB four of 3stacked MB, the+ distributionstacked trimers. trimers. Since, of the Since,as aniondiscusse as alon discussedd gabove, the channels above, the thickness the is thicknesssuch of thatthe ofanionevery the + anionmatchesanion matchesin thatembraced of that a MB ofby a fourdimer, MB +MBdimer, residual+ stacked residual spaces trimers. spaces remain Since, remain in as the discusse in anion-filled the anion-filledd above, channels. the channels. thickness Half of Half of these the of theseaniongaps gapsarematches filled are filled thatby havingof by a havingMB one+ dimer, onewater water residual molecule molecule spaces accepting accepting remain a in double a the double anion-filled hydrogen hydrogen channels.bond bond by by Halfthe the aromatic of these gaps and + aliphaticaliphaticare filled CHCH by groupsgroupshaving of ofone MBMB water+ and donatingmoleculedonating hydrogenhydrogenaccepting bondsbondsa double totoanions anionshydrogen above above bond and and by below below the (Figure aromatic(Figure4(b1)). 4b1). and + TheThealiphatic remainingremaining CH groups gapsgaps areare of MBoccupiedoccupied+ and donating byby aa MBMB+ hydrogen methyl group bonds located to anions on theabove oppositeopposite and below side withwith(Figure respectrespect 4b1). totoThe thethe remaining waterwater molecule,molecule, gaps are andand occupied donatingdonating by hydrogenhydrogen a MB+ methyl bondsbond groups toto thethe located surroundingsurrounding on the anions anionsopposite inin aaside similarsimilar with mannermanner respect asasto waterthe water molecules molecules molecule, (Figure (Figure and donating4b2).4(b2)). Since Since hydrogen the thegaps gaps bondfilled filleds byto thewater by surrounding water and andthose those filledanions filled by in the a bysimilar methyl the methyl manner group are symmetry-equivalent, the [MB+·H2O]+ units are found to be disordered in the solid phase. groupas water are molecules symmetry-equivalent, (Figure 4b2). theSince [MB the Hgaps2O] fill unitsed by are water found and to bethose disordered filled by in the the methyl solid phase.group + Consequently, in the MB stacking column,+ · every ordered pair of molecules is preceded and followed Consequently,are symmetry-equivalent, in the MB+ stacking the [MB column,·H2O] everyunits orderedare found pair to of moleculesbe disordered is preceded in the andsolid followed phase. + bybyConsequently, aa disordereddisordered in [MB[MB the+ ·HMBH2O]O]+ stacking unit unit (Figure (Figure column, 44c).c). every ordered pair of molecules is preceded and followed · 2 by a disordered [MB+·H2O] unit (Figure 4c).

Figure 4. Crystal packing of 3 viewed along the [1 0 0] and [0 1 1] crystal directions (part “a” and “b” Figure 4. Crystal packing of 3 viewed along the [1 0 0] and +[0 1 1] crystal directions (part “a” and “b” respectively). In “c”, the two parts of the disordered [MB H2O] unit are highlighted in green and +· orange,respectively).Figure 4. while Crystal theIn “ orderedpackingc”, the two speciesof 3 partsviewed are of displayed alongthe disordered the in[1 white.0 0] [MBand [0·H 12 O]1] crystalunit are directions highlighted (part in “ agreen” and and “b” orange, while the ordered species are displayed in white. respectively). In “c”, the two parts of the disordered [MB+·H2O] unit are highlighted in green and The presence of orientationally disordered [MB+ H O] units is not the only observed solution for orange, while the ordered species are displayed in white.· 2 an effiThecient presence crystal of packing orientationally of MB+ withdisordered ferricyanide [MB+·H ions.2O] units Indeed, is not the the same only synthesis observed that solution yielded for + crystalsan efficientThe of presence 3 alsocrystal produced ofpacking orientationally a secondof MB phase,with disordered ferricyanide where [MB for+ every·H ions.2O] anion unitsIndeed, thereis not the arethe same uponly to synthesis thirteenobserved independentthat solution yielded for watercrystalsan efficient molecules of 3 alsocrystal produced (Figure packing5). a Thesesecondof MB perform+ phase,with ferricyanide where a complex for every networkions. anion Indeed, of there hydrogen the are same up bondsto synthesis thirteen along independent that the yielded [0 0 1] watercrystals molecules of 3 also produced(Figure 5). a Thesesecond perform phase, where a comple for everyx network anion of there hydrogen are up bondsto thirteen along independent the [0 0 1] direction,water molecules which connects (Figure 5). all Thesethe ions perform in the solida comple phasex networkand saturates of hydrogen the aromatic bonds nitrogen along the lone [0 pair 0 1] direction, which connects all the ions in the solid phase and saturates the aromatic nitrogen lone pair

Crystals 2020, 10, 558 6 of 12 Crystals 2020, 10, x FOR PEER REVIEW 6 of 12 ofdirection, every MB which+ (Figure connects 5c). Two all the of ionsthese in water the solid molecules phase andare partially saturates substituted the aromatic with nitrogen a single lone one pair in + anof everyintermediate MB (Figure position,5c). resulting Two of these in the water unit molecules cell formula are MB partially3[Fe(CN) substituted6]·12.36H2 withO (4). a The single isolation one in an intermediate position, resulting in the unit cell formula MB [Fe(CN) ] 12.36H O (4). The isolation of the anionic species by such a large amount of solvent molecules3 and6 the· flexibility2 of the latter in adaptingof the anionic the network species of by hydrogen such a large bonding amount to the of solvent packing molecules needs of the and remaining the flexibility species of the allow latter MB in+ + toadapting perform the perfectly network ordered of hydrogen stacked bonding columns to (Figure the packing 5b). needs of the remaining species allow MB to perform perfectly ordered stacked columns (Figure5b).

Figure 5. (a) Crystal packing of 4 viewed along the [0 0 1] direction and displayed, sequentially, without water molecules, with the voids they occupy, and in their presence. (b) Stacking of MB+, where the Figurehydrogen 5. ( atomsa) Crystal are notpacking displayed of 4 viewed for the sakealong of the clarity. [0 0 (c1]) Unitdirection cell content and displayed, highlighting sequentially, the water withoutmolecule water network, molecules, focusing with on thethe dodeca-hydrate voids they occupy, type ofand unit in cell.their The presence. first three (b) molecules Stacking fromof MB the+, whereleft and the the hydrogen last three atoms on the are right not are displayed related byfor translationalthe sake of clarity. symmetry. (c) Unit cell content highlighting the water molecule network, focusing on the dodeca-hydrate type of unit cell. The first three 3.3. Packingmolecules Considerations from the left and the last three on the right are related by translational symmetry. To overview the supramolecular-interaction environment of MB+ in the obtained phases, Hirshfeld 3.3.fingerprint Packing Considerations plots were computed for each symmetry-independent cation, focussing on the contacts involvingTo overview its hydrogen, the supramolecular carbon, and nitrogen-interaction atoms environment (Figures6–9). [of22 MB,23].+ Inin allthe products, obtained the phases, strong Hirshfeldtendency fingerprint of MB+ to formplots were stacked computed columns for is ea furtherch symmetry-independent evidenced by the presence, cation, focussing in the Hirshfeld on the contactsplot, of characteristicinvolving its hydrogen, C–C contact carbon, isles centredand nitrogen at approximately atoms (Figures de 6–9).[22,23].= di = 1.8Å (highlightedIn all products, in the red strongin the figures).tendency The of shapeMB+ to of form this regionstacked is nearlycolumns symmetric is further with evidenced respect toby the the d epresence,= di axis, in hence the Hirshfeldspotlighting plot, an of overall characteristic homogeneity C–C contact of the isles stacking centred geometry at approximately and distance de = involvingdi = 1.8Å (highlighted distinct MB inmolecules. red in the In figures). particular, The ashape perfectly of this symmetric region is C–C nearly contact symmetric distribution with respect is present to the in thede = case di axis, of 2, hencewhich spotlighting is an obvious an consequence overall homo ofgeneity having of only the stacking one MB pergeometry asymmetric and distance unit and involving therefore distinct only a MBsingle molecules. MB-MB In stacking particular, geometry a perfectly is possible. symmetric As farC–C as contact finer details distribution on this is matterpresent are in the concerned, case of 2,every which phase is an showsobvious a singularconsequence combination of having ofonly O orone S MB type per of asymmetric MB stacking. unit Precisely, and therefore the stacking only a singlesequence MB-MB repeating stacking units geometry for every phaseis possible. are [–O–S–] As far for as 1,finer [–O–] details for 2, on [–O–S this/O–] matter for 3 are and concerned, [–O–S–O–] every phase shows a singular combination of O or S type of MB stacking. Precisely, the stacking sequence repeating units for every phase are [–O–S–] for 1, [–O–] for 2, [–O–S/O–] for 3 and [–O–S–

Crystals 2020, 10, 558 7 of 12 Crystals 2020, 10, x FOR PEER REVIEW 7 of 12

+ O–] for 4. Accordingly, the least symmetric Ci–Ce contact distributions between MB+ species are found for 4. Accordingly, the least symmetric Ci–Ce contact distributions between MB species are found for phases 1 and 4, which have periodic sequences of both S and O types, while the MB orientational for phases 1 and 4, which have periodic sequences of both S and O types, while the MB orientational disorder present in 3 averages out the differences between these stacking types, resulting in a much disorder present in 3 averages out the differences between these stacking types, resulting in a much less evident Ci–Ce distributions asymmetricity. As clearly displayed in the Hirshfeld plots— less evident Ci–Ce distributions asymmetricity. As clearly displayed in the Hirshfeld plots—especially especially those relative to H and N contacts—the supramolecular interaction landscape of MB is those relative to H and N contacts—the supramolecular interaction landscape of MB is different and different and strongly asymmetric in each phase due to the various molecules involved. One very strongly asymmetric in each phase due to the various molecules involved. One very distinguishable distinguishable trait, which is only exhibited by compounds 1 and 4, is the presence of hydrogen trait, which is only exhibited by compounds 1 and 4, is the presence of hydrogen bonds with the bonds with the aromatic nitrogen of MB+. This feature is evidenced by the sharp spike in the lower aromatic nitrogen of MB+. This feature is evidenced by the sharp spike in the lower half of the “Internal half of the “Internal N contacts” plot in Figures 5 and 8. In these two phases, every MB+ accepts such N contacts” plot in Figures5 and8. In these two phases, every MB + accepts such interactions from interactions from water molecules, while in phases 2 and 3, the absence or relatively scarce amount water molecules, while in phases 2 and 3, the absence or relatively scarce amount of crystallisation of crystallisation solvent leaves the lone pair of the heteroatom without significant interactions. solvent leaves the lone pair of the heteroatom without significant interactions.

+ Figure 6. Hirshfeld plots of relevant supramolecular contacts of MB in 1. The subscripts “i” and “e” means “internal” or “external”, respectively, with respect to the considered molecule. Figure 6. Hirshfeld plots of relevant supramolecular contacts of MB+ in 1. The subscripts “i” and “e” means “internal” or “external”, respectively, with respect to the considered molecule.

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Crystals 2020, 10, 558 8 of 12 Crystals 2020, 10, x FOR PEER REVIEW 8 of 12

Figure 7. Hirshfeld plots of relevant supramolecular contacts of MB+ in 2. Figure 7. Hirshfeld plots of relevant supramolecular contacts of MB+ in 2. Figure 7. Hirshfeld plots of relevant supramolecular contacts of MB+ in 2.

Figure 8. Hirshfeld plots of relevant supramolecular contacts of MB+ in 3. Figure 8. Hirshfeld plots of relevant supramolecular contacts of MB+ in 3.

Figure 8. Hirshfeld plots of relevant supramolecular contacts of MB+ in 3.

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Figure 9. Hirshfeld plots of relevant supramolecular contacts of MB+ in 4. Figure 9. Hirshfeld plots of relevant supramolecular contacts of MB+ in 4. A tentative explanation for the formation of such structures even when water molecules are A tentative explanation for the formation of such structures even when water molecules are present in the crystallisation environment could be hypothesized upon considering the atomic packing present in the crystallisation environment could be hypothesized upon considering the atomic factors (APFs) of phases 1–4 (Table1). APFs are generally defined as the ratio between the volume packing factors (APFs) of phases 1–4 (Table 1). APFs are generally defined as the ratio between the occupied by all atoms in the unit cell and the unit cell volume. These values are strongly influenced by volume occupied by all atoms in the unit cell and the unit cell volume. These values are strongly

Crystals 2020, 10, 558 10 of 12 directional interactions such as hydrogen bonds, which prioritise the energy stabilisation they provide over the overall packing efficiency, as in the case of the renowned porous structure of hexagonal ice [24]. In this regard, it is widely acknowledged in the crystal engineering community that a better crystal packing is not always synonymous with a higher occurrence likelihood when predicting the structure of polymorphic phases [25]. In our cases, the lowest APF is found for 1 (0.731), whereas 2 and 3 have remarkably better packing efficiency (APF 0.752 and 0.765, respectively). On the one hand, this difference also originates, to a large extent, from the packing motif due to the anion geometry. On the other hand, the comparison between 3 and 4 (APF value: 0.754) highlights uniquely the effects of a different phase hydration. This is observed to increase the void fraction of the phase by ~ 1.1% when water molecules participate in the packing and saturate with hydrogen bonds every lone pair present on the central nitrogen atoms of MB.

Table 1. Void volume, percentage and atomic packing factors (APFs) of the obtained phases.

Phase Void Volume (Å3) Void Fraction (%) Atomic Packing Factor MB [Ni(CN) ] 2H O 980.74 26.9 0.731 2 4 · 2 MB2[Fe(CN)5NO] 445.26 24.8 0.752 MB [Fe(CN) ] H O 585.17 23.5 0.765 3 6 · 2 MB [Fe(CN) ] 12.36H O 378.07 24.6 0.754 3 6 · 2

In summary, our results suggest that, when water molecules are present in the crystallisation medium, their participation in the crystal lattice of MB metallate salts can be driven by the need for stabilising the aromatic nitrogen lone pair. However, this need has a lower priority than optimising the infinite stacking of the cation, and when the latter requirement matches with a high packing coefficient, as in case of 2 and 3, the stabilisation of the aromatic nitrogen can be sacrificed. Compound 3 constitutes a special instance in this regard, as the non-optimal packing required a water molecule to fill the small gaps, without any possibility of hydrogen bonding with the MB+ aromatic nitrogen. The paramount priority of MB stacking among supramolecular interactions is further evidenced by considering two structures reported earlier by our group: MB chloride dihydrate and MB bisulfate [13]. These two cases exhibit the same packing motif, space group and analogous unit cell parameters as, respectively, compound 1 and 2. In the case of MB bisulfate, hydrogen-bonded dimers of the anions with an overall charge of 2 occupy the same channels where in compound 2 the nitroprusside anions − are located. This suggests that the shape, volume, and charge of the anion—or, in the cited case, of its dimer—generally play a more relevant role than its internal chemical structure. This aspect ceases to be relevant in the cases of chloride and tetracyanonickelate ions, which have totally different charge, shape, and volume, and yet lead to the formation of two iso-packed phases, therefore leaving MB+ infinite stacking columns as the main leading packing prerequisite. In conclusion, our study highlights how the challenge of predicting the formation of hydrate phases can be addressed by identifying and ranking the supramolecular interactions needs of the involved species. Its validity should not be limited to molecular salts but may also be considered for other non-ionic products of crystal engineering such as co-crystals and supramolecular assemblies in general. In fact, taking into consideration both packing efficacy and the requirements of specific types of interactions of the species involved, combinatorial studies of the type we have shown can spotlight hierarchies in the energy landscape of crystal phases, which can assist in the prediction of the presence and role of water molecules in the overall supramolecular architecture.

Supplementary Materials: The following are available online at http://www.mdpi.com/2073-4352/10/7/558/s1, additional details on the single-crystal XRD analysis of the described compounds can be found in the supplementary materials, available free of charge on the publisher’s website. Author Contributions: All authors contributed significantly to this work. Further details are reported as follows. Synthesis: S.C., D.C.; crystallographic analysis: S.C., C.G.; supervision: G.P., C.G., manuscript writing and graphics: S.C. All authors have read and agreed to the published version of the manuscript. Crystals 2020, 10, 558 11 of 12

Acknowledgments: The Elettra Synchrotron (CNR Trieste) is gratefully acknowledged for the beamtime allocated at the beamline XRD1 (proposal nr 20175216). S.C. acknowledges the Research Foundation Flanders (FWO) for supporting his research (grant nr. 12ZV120N). Conflicts of Interest: The authors declare no conflict of interest.

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