chemosensors Review Luminescent Metal Nanoclusters for Potential Chemosensor Applications Muthaiah Shellaiah 1 and Kien Wen Sun 1,2,* 1 Department of Applied Chemistry, National Chiao Tung University, Hsinchu 300, Taiwan; [email protected] 2 Department of Electronics Engineering, National Chiao Tung University, Hsinchu 300, Taiwan * Correspondence: [email protected] Received: 21 November 2017; Accepted: 8 December 2017; Published: 19 December 2017 Abstract: Studies of metal nanocluster (M-NCs)-based sensors for specific analyte detection have achieved significant progress in recent decades. Ultra-small-size (<2 nm) M-NCs consist of several to a few hundred metal atoms and exhibit extraordinary physical and chemical properties. Similar to organic molecules, M-NCs display absorption and emission properties via electronic transitions between energy levels upon interaction with light. As such, researchers tend to apply M-NCs in diverse fields, such as in chemosensors, biological imaging, catalysis, and environmental and electronic devices. Chemo- and bio-sensory uses have been extensively explored with luminescent NCs of Au, Ag, Cu, and Pt as potential sensory materials. Luminescent bi-metallic NCs, such as Au-Ag, Au-Cu, Au-Pd, and Au-Pt have also been used as probes in chemosensory investigations. Both metallic and bi-metallic NCs have been utilized to detect various analytes, such as metal ions, anions, biomolecules, proteins, acidity or alkalinity of a solution (pH), and nucleic acids, at diverse detection ranges and limits. In this review, we have summarized the chemosensory applications of luminescent M-NCs and bi-metallic NCs. Keywords: nanoclusters; fluorescent assay; nanosensors; bio-imaging; real analysis; colorimetric recognition; biomolecules detection; bi-metallic clusters 1. Introduction Metal nanoclusters (M-NCs) have attracted the attention of the modern scientific community, because of their cost effective synthesis, biocompatibility, photostability, and wide applications [1–5]. M-NCs consist of few atoms (mostly between ten to hundred) of comparable sizes similar to the Fermi wavelength of electrons [6–8]. Hence, M-NCs can be considered as the missing link between single metal atoms and plasmonic metal nanoparticles [9]. In contrast to plasmonic nanoparticles, M-NCs have a size less than 2 nm [10,11] and do not exhibit any plasmonic characteristics. In addition, upon interaction with light, M-NCs display absorption and emission properties via electronic transitions between energy levels as in the case of organic molecules [12]. Therefore, in recent times, researchers have tended to apply M-NCs in various studies such as chemosensors, biological imaging, catalysis, as well as environmental and electronic devices. Chemo- and bio-sensory applications of luminescent M-NCs have attained most impressive progress [13–15]. Luminescent NCs of Au, Ag, Cu, and Pt have been successfully utilized as potential sensory materials [16–23]. Similar to organic fluorophores, carbon dots (CDs), and fluorescent quantum dots (QDs), luminescent M-NCs have been successfully applied in many sensor investigations because of their fluorescent nature, ultra-small size, and biocompatibility. Luminescent M-NCs have also been utilized in many in vivo/vitro biological imaging studies [24–27]. The stability of M-NCs has been improved using stabilizing agents. Chemosensors 2017, 5, 36; doi:10.3390/chemosensors5040036 www.mdpi.com/journal/chemosensors Chemosensors 2017, 5, 36 2 of 30 Chemosensors 2017, 5, 36 2 of 31 utilized in many in vivo/vitro biological imaging studies [24–27]. The stability of M-NCs has been improved using stabilizing agents. The presencepresence of of templates templates on on the the surface surface of M-NCs of M-NCs canimprove can improve the stability the stability and enhance and enhance sensing abilitysensing by ability providing by providing a binding a unitbinding on the unit surface. on the For surface. example, For template-protectedexample, template-protected Au NCs have Au beenNCs previouslyhave been reportedpreviously as extended reported analytical as extended tools foranalytical species detectiontools for [ 28species]. These detection templates/stabilizers [28]. These cantemplates/stabilizers also improve the can luminescent also improve property the luminesc and biocompatibilityent property and of thebiocompa clusters.tibility Similar of the to Auclusters. NCs, otherSimilar metal to Au NCs NCs, (Ag, other Cu, metal and PtNCs NCs) (Ag, have Cu, and displayed Pt NCs) comparable have displayed fluorescent comparable properties fluorescent in the presenceproperties of in various the presence stabilizers of various [29–31 stabilizers]. Therefore, [29–31]. M-NCs Therefore, are formed M-NCs by are reducing formed metal by reducing ions in themetal presence ions in of the appropriate presence reducingof appropriate agents. reducing Thiols, dendrimers, agents. Thiols, polymers, dendrimers, DNA oligonucleotides,polymers, DNA peptides,oligonucleotides, and proteins peptides, have beenand proteins commonly have used been to stabilize commonly or improve used to the stabilize opto-electric or improve properties the ofopto-electric M-NCs [32 properties]. of M-NCs [32]. Scholars have reported variousvarious applicationsapplications ofof luminescentluminescent bi-metallicbi-metallic NCs.NCs. Bi-metallic NCs can be developed through different synthetic techniques,techniques, such as (1) galvanic replacement reaction, (2) anti-galvanicanti-galvanic replacementreplacement reaction,reaction, (3) potentialpotential deposition,deposition, (4) thiol-etchingthiol-etching of bi-metallicbi-metallic nanoparticles, and and (5) (5) re-organization re-organization of of bi-metallic bi-metallic species species [33]. [33 To]. date, To date, Au-Ag, Au-Ag, Au-Cu, Au-Cu, Au-Pd, Au-Pd, and andAu-Pt Au-Pt NCs NCshave havebeen utilized been utilized in various in various fields, such fields, as such catalysis, as catalysis, sensors, sensors,and bio-imaging. and bio-imaging. Overall, Overall,chemosensor chemosensor applications applications of both of M-NCs both M-NCs and bi-metallic and bi-metallic NCs NCshave have attracted attracted interest interest because because of oftheir their cost-effective cost-effective operation operation in inbiological biological and and environmental environmental samples. samples. Both metallic metallic and and bi-metallic bi-metallic NCs NCs have have been been effe effectivelyctively applied applied to detect to detect various various analytes, analytes, such suchas metal as metal ions, ions,anions, anions, biomolecules, biomolecules, proteins, proteins, pHs, pHs,and andnucleic nucleic acids. acids. Furthermore, Furthermore, metallic metallic and andbi-metallic bi-metallic NCs NCshave have also alsobeen been reported reported as suitable as suitable candidates candidates for bio-imaging. for bio-imaging. In this In thisreview, review, we wesummarize summarize the thechemosensory chemosensory applications applications of luminescent of luminescent M-NCs M-NCs (M (M= Au, =Au, Ag, Ag,Cu, Cu,and and Pt),Pt), as aspresented presented in inFigure Figure 1.1 .In In addition, addition, we we provide provide a a brief brief note note on the sensorysensory applicationsapplications ofof otherother M-NCs (such as Cd, Al, Pd, and Ir NCs) and bi-metallicbi-metallic NCs.NCs. Figure 1. Schematic representation of chemosensor applicationsapplications of metal nanoclustersnanoclusters (M-NCs). 2. Optimization Requirements The sensorysensory and and bio-imaging bio-imaging applications applications of M-NCs of M-NCs are dependent are dependent on the following on the requirements, following whichrequirements, must be which optimized must before be optimize designingd before such designing probes. such probes. A. Ligands:Ligands: Suitable Suitable ligands ligands must must be be selected selected to to achieve achieve enhanced enhanced fluorescence fluorescence and tunable emissiveemissive colors, colors, such such as as blue, blue, green, green, red, red, orange, orange, and and yellow. yellow. Thiols, Thiols, dendrimers, polymers, DNA-oligonucleotides,DNA-oligonucleotides, peptides, peptides, and andproteins proteins have havebeen commonly been commonly used as used ligands. as ligands.Among them,Among ligands them, consisting ligands of consisting thiol groups of thiol havegroups displayed have outstanding displayed results outstanding [34]. For results example, [34]. HuangFor example, and Goswami’s Huang and reports Goswami’s [35,36] reportson Au [NC35,36s ]described on Au NCs the described use of thiolated the use ofligands thiolated for capping.ligands In for both capping. studies, In diverse both studies, emissive diverse colors emissivewere observed colors by were optimizing observed the by ligand optimizing or its concentrations.the ligand or Several its concentrations. NC specimens Several are presen NCted specimens in this paper are presented with various in this ligands, paper which with various ligands, which have been already explored in many sensor studies. Thus, selection Chemosensors 2017, 5, 36 3 of 31 of suitable ligands and optimization of their concentration play vital roles in the luminescent property of NCs. B. Quantum Yield (F): The quantum yield (F) of the probe should be effectively tuned by optimizing the reaction conditions, functionalizing the appropriate ligands at affordable concentration, and selecting solvents for assay methods to maximize the application of luminescent M-NCs in analyte detection.