Zinc-Ion-Induced Aggregation of Gold Clusters for Visible-Light-Excitation-Based Fluorimetric Discrimination of Geometrical Isomers.

Herein, we report discrimination of dicarboxylic acids - fumaric acid (FA) and maleic acid (MA) - exhibiting geometrical isomerism, using nanoclusters based luminescent probe having excitation under broad day light. The luminescent probe was designed via complexation reaction between zinc ions and ligands (mercaptopropioinc acid; MPA) stabilizing the gold nanoclusters. This resulted in formation of nanoaggregates exhibiting bright green luminescence upon excitation at 450 nm capable of discriminating between FA and MA upto nanomolar level. The basis of discrimination has been attributed to deprotonation of FA and MA following interaction with MPA moieties present on the surface of the nanoaggregates and being governed by the stability of the respective conjugate base of the geometrical isomers of the dicarboxylic acids. As a consequence of different extent of deprotonation of FA and MA upon interaction with the cluster aggregates, different effect on the luminescence of the aggregates was observed, thus enabling discernible fluorimetric discrimination between FA and MA under visible light excitation.

Tailoring the luminescence of atomic clusters via ligand exchange reaction mediated post synthetic modification.

The growing prominence of atomic nanoclusters in fields of practical relevance has made modulation of their luminescent characteristics an important challenge for their future applications. Herein we report chemical reaction assisted modulation of luminescence of histidine stabilized gold nanoclusters via a ligand exchange reaction with cysteine. Upon addition of 3.8 mM cysteine, as evinced by X-ray photoelectron spectroscopy in conjunction with transmission electron microscopic analyses, histidine molecules were found to desorb from the surface of the Au NCs leading to the latter's aggregation into macroscopic units. Consequently, the luminescence of the His Au NCs underwent a large bathochromic shift from 475 nm to 500 nm with a concomitant decrease in the luminescence intensity. Thereafter, upon addition of 18 mM cysteine to a dispersion of His Au NCs, cysteine molecules by virtue of strong aurophilic interactions were found to adsorb on to the surface of the Au NCs, leading to the disaggregation of the macroscopic structures. This was accompanied by restoration of the luminescence features of the Au NCs to an emission maximum of 486 nm with partial recovery of the luminescence intensity. Thus, the work embodied herein demonstrates post-synthetic chemical reactions of nanoclusters as an effective and viable tool for tailoring the photoluminescence of atomic clusters to meet application demands.

Crystallization-Induced Emission Enhancement of Nanoclusters and One-Step Conversion of "Nanoclusters to Nanoparticles" as the Basis for Intracellular Logic Operations.

Herein, we report the construction of intracellular logic operations using luminescent histidine stabilized gold nanoclusters (His Au NCs). The luminescence intensity of His Au NCs was found to be significantly enhanced following interaction with zinc ions, owing to "Crystallization induced emission enhancement". Further, the luminescence intensity of His Au NCs was found to be effectively quenched in presence of sulphide ions, owing to transformation of emissive His Au NCs to non-emissive gold nanoparticles. Thus, the collective and individual effects of zinc ions and sulphide ions causing significant variation in the luminescence intensity of His Au NCs, were used as input parameters for construction of intracellular logic operations such as Tri state buffer, "on-off" switch and INHIBIT gate within mammalian cells.

Visible Light Excitation-Induced Luminescence from Gold Nanoclusters Following Surface Ligand Complexation with Zn2+ for Daylight Sensing and Cellular Imaging.

Herein, we report a complexation reaction-mediated extended aggregation of gold nanoclusters exhibiting luminescence under visible light excitation. The complexation reaction between the carboxylate groups of mercaptopropionic acid and zinc ions induced the aggregation of gold nanoclusters, which featured bright green luminescence upon excitation with visible light of wavelength 450 nm and beyond. This luminescence of aggregated Au NCs, easily discernible with bare eyes (under broad daylight excitation), was used as a probe for luminescence-based detection of molecules based on the p Ka values of the latter. This aspect has been an unfilled dream of scientists pursuing research on the development of nanoscale sensors, as luminescence-based detection techniques offer a greater degree of accuracy and sensitivity compared to absorption-based methods, and was thus far an unexploited/untapped area by nanoscale materials. Moreover, facile imaging of mammalian cells was achieved using these aggregated clusters upon excitation with visible light. This study demonstrates the utility of luminescent nanoclusters, akin to organic dyes, as materials active under visible light excitation. Thus, the complexation reaction-based tailoring of the optical properties of nanoclusters served as an effective tool in pushing the absorption maxima of the nanoclusters from an ultraviolet to visible range, enabling the luminescence of nanoclusters under broad daylight excitation. Hence, the work embodied herein offers a unique route to widen the application potential of metal nanoclusters as sensors and bioimaging agents operating under visible light excitation.

Photo induced chemical modification of surface ligands for aggregation and luminescence modulation of copper nanoclusters in the presence of oxygen.

Surface modification of nanoparticles has been a popular approach to tailor the properties of nanoparticles. Herein we report the unprecedented photo oxidation of cysteine moeties on the surface of copper nanoclusters (Cu NCs) leading to aggregation of Cu NCs, which further led to quenching of luminescence of the latter. Upon illumination of a dispersion of Cu NCs at 365 nm wavelength light, the luminescence of Cu NCs was completely quenched. Furthermore, the extent of luminescence quenching of Cu NCs upon photo illumination could be tuned by varying the area of exposure of light. Confirmation of photooxidation of cysteine molecules was made through Fourier transformed infrared (FTIR) studies, while the formation of submicron sized aggregates of Cu NCs as a result of photo oxidation of cysteine stabilizing the nanoclusters was evinced through transmission electron microscopy (TEM). The study embodied herein opens up new avenues for the tailoring of the chemical and optical properties of metal nanoclusters through chemical transformation of surface ligand moieties, which is envisioned to emerge as a powerful strategy for broadening the application potential of metal nanoclusters.

Zinc-Coordinated Hierarchical Organization of Ligand-Stabilized Gold Nanoclusters for Chiral Recognition and Separation.

Three-dimensional organization of d- or l-tryptophan and mercaptopropionic acid-stabilized gold nanoclusters has been achieved by complexation of ligands using zinc ions. Powder X-ray diffraction and transmission electron microscopy analyses substantiated the crystalline nature of the assembly of atomic nanoclusters. The hierarchical arrangement of the nanoclusters exhibited superior optical properties (namely, enhanced photoluminescence and excited-state lifetime) as compared to the non-assembled nanoclusters. Furthermore, photoluminescence of the crystalline assembly of nanoclusters served as a visual marker for chiral recognition of d and l enantiomers of tryptophan, with subsequent separation of the corresponding enantiomer. A theoretical structure based on various experimental observations has also been proposed herein. The mechanistic aspect of the chiral separation is proposed to have occurred through attachment of d or l-tryptophan to the coordinatively unsaturated zinc ions, thus forming super complexes. The degree of stabilization of the super complexes is dictated by a "three-point versus two-point" interaction between the enantiomers and the chiral selector.

An Interactive Quantum Dot and Carbon Dot Conjugate for pH-Sensitive and Ratiometric Cu2+ Sensing.

Herein we report the photoinduced electron transfer from Mn2+ -doped ZnS quantum dots (Qdots) to carbon dots (Cdots) in an aqueous dispersion. We also report that the electron transfer was observed for low pH values, at which the oppositely charged nanoparticles (NPs) interacted with each other. Conversely, at higher pH values the NPs were both negatively charged and thus not in contact with each other, so the electron transfer was absent. Steady-state and time-resolved photoluminescence studies revealed that interacting particle conjugates were responsible for the electron transfer. The phenomenon could be used to detect the presence of Cu2+ ions, which preferentially, ratiometrically, and efficiently quenched the luminescence of the Qdots.

Optically definable reaction-diffusion-driven pattern generation of Ag-Au nanoparticles on templated surfaces.

We introduce a new lithographic method for the generation of 2D patterns of composite nanoparticles (NPs) of Ag and Au by taking recourse to combine top-down and bottom-up approaches. Micrometer-scale and submicrometer-scale patterned Ag foils of commercially available compact disks (CDs) and digital versatile disks (DVDs), respectively, were used as templates. The galvanic replacement reaction of Ag by HAuCl(4) in the presence of the dye coatings on the foils led to the formation of patterned NP composites of Ag and Au, in addition to the formation of AgCl. The resultant structures appeared in the form of cross patterns of particles with micrometer and submicrometer dimensions. The AgCl crystals thus formed could be removed by using either a saturated NaCl solution or aqueous ammonia. In addition, AgCl could be converted to Ag by electrochemical reduction, thus generating Ag-coated Au NPs. Interestingly, the digital writing on CDs led to the formation of tertiary imprints on the patterns, based on the original writing patterns. This provided an additional handle in generating hierarchical patterns using light in combination with a chemical reaction diffusion process and the nearly parallel line patterns originally present in commercial CDs. The reactions could be carried out in aqueous solution, and the method does not require any additional curing. Also, the density of patterned particles is scalable on the basis of the choice of the original line patterns as present in CDs and DVDs.

Controlling the Chemistry of Nanoclusters: From Atomic Precision to Controlled Assembly.

Metal nanoclusters have gained prominence in nanomaterials sciences, owing to their atomic precision, structural regularity, and unique chemical composition. Additionally, the ligands stabilizing the clusters provide great opportunities for linking the clusters in higher order dimensions, eventually leading to the formation of a repertoire of nanoarchitectures. This makes the chemistry of atomic clusters worth exploring. In this mini review, we aim to focus on the chemistry of nanoclusters. Firstly, we summarize the important strategies developed so far for the synthesis of atomic clusters. For each synthetic strategy, we highlight the chemistry governing the formation of nanoclusters. Next, we discuss the key techniques in the purification and separation of nanoclusters, as the chemical purity of clusters is deemed important for their further chemical processing. Thereafter which we provide an account of the chemical reactions of nanoclusters. Then, we summarize the chemical routes to the spatial organization of atomic clusters, highlighting the importance of assembly formation from an application point of view. Finally, we raise some fundamentally important questions with regard to the chemistry of atomic clusters, which, if addressed, may broaden the scope of research pertaining to atomic clusters.

Four orders-of-magnitude enhancement in the two-photon excited photoluminescence of homoleptic gold thiolate nanoclusters following zinc ion-induced aggregation.

Herein we report unprecedented determination of the molar mass of zinc mediated assemblies of homoleptic gold nanoclusters, based on charge detection mass spectrometry measurements. The accurate determination of the molar mass of zinc coordinated assemblies of gold clusters has further allowed unambiguous determination of the two-photon excited photoluminescence cross section of the same. Furthermore, in line with one-photon excited photoluminescence measurements, four orders-of-magnitude enhancement in two-photon excited photoluminescence of gold nanoclusters has been observed following complexation with zinc ions. The study reported herein is envisioned to not only deepen the fundamental understanding of the multiphoton excitation properties of atomic clusters but also widen their application potential as luminescence markers.

Heightened reactive oxygen species generation in the antimicrobial activity of a three component iodinated chitosan-silver nanoparticle composite.

Herein we report synergy in antimicrobial activity of a chitosan-silver nanoparticle (CS-Ag NP) composite in the presence of molecular iodine. Green fluorescent protein (GFP) expressing recombinant Escherichia coli bacteria have been used to test the efficacy and establish the mechanism of action. Experimental evidence indicate significantly high bactericidal activity of the nanocomposite in the presence of iodine than either due to the composite, chitosan, Ag NP or iodine only. Transmission electron microscopy measurements revealed attachment of bacteria to the composite. In addition, flow cytometry results supported definite occurrence of cell wall damage of the bacteria treated with the composite in the presence of iodine. Further, the nanocomposite and iodine combination was found to exert reactive oxygen species (ROS) generated oxidative stress in the cytoplasm of bacterial cells, leading to cell death. Elucidation of the mechanism of synergy due to three potential antibacterial components suggested that on the surface of Ag NPs molecular iodine possibly generated iodine atom thus contributing toward free radical induced oxidative stress, whereas chitosan and Ag NPs facilitated the process of cell killing and thus collectively enhanced the potency of antimicrobial effect at the lowest concentrations of individual components.

Protein-Nanoparticle Agglomerates as a Plasmonic Magneto-Luminescent Multifunctional Nanocarrier for Imaging and Combination Therapy.

We report the fabrication of a plasmonic magneto-luminescent multifunctional nanocarrier (PML-MF nanocarrier) by lysozyme-mediated agglomeration of gold-coated iron oxide nanoparticles (IO@AuNPs) and subsequent coating of these agglomerates with BSA-stabilized gold nanoclusters (BSA-AuNCs). The agglomeration-mediated enhancement of plasmonic absorbance at the NIR biological window helped in plasmonic photothermal therapy (PPTT) by PML-MF nanocarriers. PML-MF nanocarriers demonstrated excellent in vitro bioimaging and magnetic targeting capabilities due to the strong photoluminance and superparamagnetism of the constituent AuNCs and IO@AuNPs, respectively. Moreover, these nanocarriers showed the successful loading and delivery of doxorubicin to cancer cells with a significant killing efficiency that could be synergistically improved by combining with PPTT.

Crystalline assembly of gold nanoclusters for mitochondria targeted cancer theranostics.

Herein, we report the formation of a crystalline assembly of gold (Au) nanoclusters for cancer theranostics via active targeting of mitochondria. To the best of our knowledge, this is the first report of the target specific activity of an "assembly of gold nanoclusters". Au14 nanoclusters were stabilized with mercaptopropionic acid and l-tyrosine. The limited solubility of l-tyrosine in methanolic solution led to the formation of a polycrystalline assembly of Au nanoclusters via interactions between ligands (tyrosine) stabilizing the clusters. Further, complexation reaction between zinc ions and ligands stabilizing the Au nanoclusters led to the formation of a single crystalline assembly of gold nanoclusters. Transmission electron microscopic and selected area electron diffraction analyses revealed the formation of faceted crystals with a hexagonal arrangement of Au14 nanoclusters. A theoretical structure of the crystalline complex of Au nanoclusters and zinc ions has been proposed herein based on experimental observations and computational optimization. The crystalline assembly of Au nanoclusters, formed via ligand association as well as complexation reaction, exhibited mitochondria targeted anti-cancer activity - as verified by Mito Tracker staining experiments. However, the MTT assay, FACS analysis and JC-1 staining experiments revealed that the zinc mediated assembly of Au nanoclusters exhibited superior therapeutic action as compared to the methanol driven assembly of the clusters.

Synergistic Anticancer Potential of Artemisinin When Loaded with 8-Hydroxyquinoline-Surface Complexed-Zinc Ferrite Magnetofluorescent Nanoparticles and Albumin Composite.

Herein, we report the fabrication of a novel class of magnetofluorescent theranostic nanoparticles (MFTNPs) based on "surface-complexation" of zinc ferrite (ZnFe2O4) NPs with 8-hydroxyquinoline. The potential of these MFTNPs in fluorescence-based bioimaging of different cancer cells was successfully demonstrated. The superparamagnetic behavior of the MFTNPs was exploited effectively in magnetic targeting in vitro. Finally, a well-known hydrophobic antimalarial and prospective anticancer drug artemisinin was efficiently loaded into MFTNPs. Artemisinin loaded MFTNPs were observed to induce superior antiproliferative response, as compared to free drug, in cancer cells in a synergistic mechanism with combination index of 0.1 or less.

Protein-Based Multifunctional Nanocarriers for Imaging, Photothermal Therapy, and Anticancer Drug Delivery.

We report a simple approach for fabricating plasmonic and magneto-luminescent multifunctional nanocarriers (MFNCs) by assembling gold nanorods, iron oxide nanoparticles, and gold nanoclusters within BSA nanoparticles. The MFNCs showed self-tracking capability through single- and two-photon imaging, and the potential for magnetic targeting in vitro. Appreciable T2-relaxivity exhibited by the MFNCs indicated favorable conditions for magnetic resonance imaging. In addition to successful plasmonic-photothermal therapy of cancer cells (HeLa) in vitro, the MFNCs demonstrated efficient loading and delivery of doxorubicin to HeLa cells leading to significant cell death. The present MFNCs with their multimodal imaging and therapeutic capabilities could be eminent candidates for cancer theranostics.

Electrochemical actuation of growing copper dendrimers in water.

We report the observation of electrochemical actuation in growing dendritic fibers made of self-assembled copper nanostructures (of 100 nm or less in diameter), on the metallic cathode of an ordinary aqueous electrochemical cell. This could be achieved when a copper anode and another metal cathode is placed in aqueous solution of either dilute HCl or CuSO(4), or CuCl(2), or H(2)O, and upon application of a DC voltage in the range of 1.5-12.0 V. The actuation could be observed with an on-off cycle of the applied voltage in the above range. The phenomenon was also observed with the growth of bimetallic structures using a number of electrolytes such as Ag(NO(3)), Pb(NO(3))(2), CoCl(2), NiCl(2), CdCl(2), ZnCl(2), and HAuCl(4). The fibrous structures remained stretched as they grew longer with time in the presence of an applied voltage. The extent of actuation was dependent on the applied voltage, the concentration of Cu(2+) ions in the solution, and also on ions such as Na(+), which did not get deposited at the cathode. The observed phenomena under different conditions have been explained on the basis of electrocapillarity.

Thumb Imprint Based Detection of Hyperbilirubinemia Using Luminescent Gold Nanoclusters.

Early and easy detection of diseases, using point-of-care and inexpensive devices, not only provides option for early treatment but also reduces the risk of propagation. Herein we report the fabrication of a robust film based luminescence indicator of bilirubin, which can indicate hyperbilirubinemia through the thumb imprint of the patient. The UV-light induced luminescence intensity of the film, made out of chitosan stabilised gold (Au) nanoclusters, which was effectively quenched in the presence of Cu2+ ions, recovered in the presence of bilirubin from skin or blood serum. Moreover, the sensitivity of detection of bilirubin was tuneable with the amount of Cu2+ added, thereby facilitating the detection of the desired concentration range of bilirubin.

Observations of the effect of anionic, cationic, neutral, and zwitterionic surfactants on the Belousov-Zhabotinsky reaction.

In this paper we report the experimental observations of the effects of various surfactants on the oscillations of the ferroin-catalyzed Belousov-Zhabotinsky (BZ) reaction. The oscillations are followed by observing the change in absorbance at 510 nm due to ferroin in a well-stirred closed BZ reacting system. We have used sodium dodecyl sulfate (SDS) as the anionic surfactant, cetyl trimethylammonium bromide (CTAB) as the cationic surfactant, Triton X-100 as the neutral surfactant, and 3-[(3-cholamidopropyl)dimethylammonio)]-1-propanesulfonate (CHAPS) as the zwitterionic surfactant. In general, we observed that there is a change in the oscillation behavior in the presence of each of these surfactants above their critical micellar concentrations. For different surfactants, the time-dependent evolution of the oscillations is found to be characteristic of the surfactant. The results of our study suggest that the evolution of oscillations is most regular in the presence of micelles of SDS.

Theranostic potential of gold nanoparticle-protein agglomerates.

Owing to the ever-increasing applications, glittered with astonishing success of gold nanoparticles (Au NPs) in biomedical research as diagnostic and therapeutic agents, the study of Au NP-protein interaction seems critical for maximizing their theranostic efficiency, and thus demands comprehensive understanding. The mutual interaction of Au NPs and proteins at physiological conditions may result in the aggregation of protein, which can ultimately lead to the formation of Au NP-protein agglomerates. In the present article, we try to appreciate the plausible steps involved in the Au NP-induced aggregation of proteins and also the importance of the proteins' three-dimensional structures in the process. The Au NP-protein agglomerates can potentially be exploited for efficient loading and subsequent release of various therapeutically important molecules, including anticancer drugs, with the unique opportunity of incorporating hydrophilic as well as hydrophobic drugs in the same nanocarrier system. Moreover, the Au NP-protein agglomerates can act as 'self-diagnostic' systems, allowing investigation of the conformational state of the associated protein(s) as well as the protein-protein or protein-Au NP interaction within the agglomerates. Furthermore, the potential of these Au NP-protein agglomerates as a novel platform for multifunctional theranostic application along with exciting future-possibilities is highlighted here.

Synergistic anticancer activity of fluorescent copper nanoclusters and cisplatin delivered through a hydrogel nanocarrier.

Highly fluorescent red copper nanoclusters (Cu NCs) were synthesized in aqueous medium in the presence of dihydrolipoic acid and poly(vinylpyrrolidone) (PVP). The Cu NCs, in solid form, were stable, retained their optical properties for a month, and could be redispersed for use when required. The NCs in aqueous medium exhibited pH-tunable reversible optical properties. The PVP stabilized NCs, when converted into hydrogel by cross-linking with poly(vinyl alcohol), delivered anticancer drug to cervical cancer (HeLa) cells, thereby inducing apoptotic cell death. The red emission properties of the Cu NCs in the hydrogel were used for optical imaging as well as for flow cytometric probe of cellular uptake. Cell viability assay, Caspase3 assay, and cell cycle analyses demonstrated that the Cu NCs present in the hydrogel composite exhibited synergy of action, along with the drug, cisplatin, against HeLa cells.