The aims of this study were to establish if insulin conjugated with auric gold Au(III) can be visualized in living cells expressing insulin receptors, and if key steps in insulin signaling are undisturbed. Au(III) is coordinated with three tyrosines of insulin and is strongly stabilized by coordination with these tyrosines into a metal-ion coordinated insulin template. We combined theoretical and experimental approaches, including computational analyses, immunocytochemistry and functional assays to analyze the cellular effects of this construct. Results in this study show that the insulin-Au(III) conjugate does not impair several steps in insulin signaling and downstream metabolic functions in lysosomes and lipid droplets. Namely, the signaling kinases protein kinase B (Akt1) and mitogen-activated protein kinases (ERK1/2) are phosphorylated to a comparable extent as with unmodified insulin. Immunocytochemistry also shows a comparable decrease in nuclear transcription factor EB (TFEB), an essential regulator of lysosomal biogenesis. Fluorescence co-labelling of lysosomes with LysoTracker and lipid droplets with BODIPY 493/503 shows normal organellar morphology and slightly enhanced lipid droplet content. The luminescent properties of insulin-Au(III) could serve to combine biochemical and imaging studies in human cells beyond microglia.

It remains a prime question of how to describe the optical properties of large molecular clusters accurately. Quantum chemical methods capture essential electronic details but are infeasible for entire clusters, while optical simulations handle cluster-scale effects but miss crucial quantum effects. To overcome such limitations, we apply here a multi-scale modeling approach, combining precise quantum chemistry calculations with Maxwell scattering simulations, to study the linear and nonlinear optical response of finite-size supramolecular gold-cysteine nanoparticles dispersed in water. In this approach, every molecular unit that forms the cluster is represented by a polarizability and a hyperpolarizability, and the overall response is obtained from solving an optical multiple scattering problem. We particularly demonstrate how important it is to accurately consider the environment of the individual molecular units when computing their polarizability and hyperpolarizability. In our quantum chemical simulations, we do so at the level of a static partial charge field that represents the presence of other molecular units. Without correctly considering these effects of the embedding, predictions would deviate from experimental observations even qualitatively. Our findings pave the way for more accurate predictions of the optical response of complex molecular systems, which is crucial for advancing applications in nanophotonics, biosensing, and molecular optoelectronics.

This study focuses on the modulatory effects of gold nanoclusters with 25 gold atoms and 18 acetyl cysteines (Au25AcCys18) in human microglia, human iPSC-derived neurons and SH-SY5Y differentiated human neuronal cells. The combination of chemical, biological, and computational methods shows the well-retained viability of these human cells treated with Au25AcCys18, interactions between Au25AcCys18 and transcription factor TFEB (computational approach), interactions between TFEB and HMGB1 (proximity ligation assay and molecular modeling using AlphaFold), modulation of the abundance and location of acHMGB1 by Au25AcCys18 (immunocytochemistry), and the reduction of ROS in cells treated with Au25AcCys18 (CellROX live imaging). These novel findings in human neural cells, particularly neurons, encourage further studies in experimental animal models of neurological disorders and/or human organoids to exploit the unique structural and photophysical properties of gold nanoclusters and to better understand their ability to modulate molecular mechanisms in human cells.

Red luminophores displaying large Stokes shift and high-quantum yields are obtained when gold salts are reacted with proteins under strongly alkaline conditions. Although bovine serum albumin (BSA) has mainly been used as a protein template, other attempts to prepare red luminophores have been proposed using other proteins. Here, we report on the structural characterization and nonlinear optical properties of insulin-gold conjugates. Such conjugates display strong luminescence at ∼670 nm with quantum yields that reach 5.4%. They also display long luminescence lifetimes allowing efficient reactive oxygen species generation, with a quantum yield of 1O2 generation reaching 13%. In addition, they exhibit remarkable nonlinear optical properties and in particular a strong two-photon excited fluorescence (TPEF) cross section in the range of 800-1100 nm. By combining experimental studies and time-dependent density functional theory simulations (TD-DFT), we show the formation of insulin-Au(III) conjugates. The interaction of Au(III) ions with the aromatic rings of tyrosine induces charge transfer-like excitation in the visible range. Experimental investigations, together with molecular dynamics simulations of insulin and calculations of electronic properties in a model system, are performed to explore the origin of optical features and the structure-optical property relationship, leading the way to new concepts for nonlinear optics using protein-Au(III) conjugates.

SQA J-aggregates as material for transparent luminescent solar concentators (TLSC).

Identification of a natural-based sensitizer with optimal stability and efficiency for dye-sensitized solar cell (DSSC) application remains a challenging task. Previously, we proposed a new class of sensitizers based on bio-nano hybrids. These systems composed of natural cyanidin dyes interacting with silver nanoclusters (NCs) have demonstrated enhanced opto-electronic and photovoltaic properties. In this study, we explore the doping of silver nanocluster within a cyanidin-Ag3 hybrid employing Density Functional Theory (DFT) and its time-dependent counterpart (TDDFT). Specifically, we investigate the influence of coinage metal atoms (Au and Cu) on the properties of the cyanidin-Ag3 system. Our findings suggest that cyanidin-Ag2Au and cyanidin-AgAuCu emerge as the most promising candidates for improved light harvesting efficiency, increased two-photon absorption, and strong coupling to the TiO2 surface. These theoretical predictions suggest the viability of replacing larger silver NCs with heterometallic trimers such as Ag2Au or AgAuCu, presenting new avenues for utilizing bio-nano hybrids at the surface for DSSC application.

Theoretical study of structural, optical, and photovoltaic properties of novel bio-nano hybrids (dye-nanocluster), as well as at TiO2 surface model support is presented in the context of the application for dye-sensitized solar cells (DSSC). A group of anthocyanidin dyes (pelargonidin, cyanidin, delphinidin, peonidin, petunidin, and malvidin) represented by cyanidin covalently bound to silver nanoclusters (NCs) with even or odd number of valence electrons have been investigated using DFT and TDDFT approach. The key role of nanoclusters as acceptors in hybrids cyanidin-NC has been shown. The nanoclusters with an even number of valence electrons are suitable as acceptors in hybrids. The interaction of bio-nano (cyanidin-NC) hybrid with the TiO2 surface model has been investigated in the context of absorption in near-infrared (NIR) and charge separation due to donor and acceptor subunits. Altogether, the theoretical concept serves to identify the key steps in the design of novel solar cells based on bio-nano hybrids at TiO2 surface for DSSC application.

This themed collection includes a collection of articles on stability and properties of new-generation metal and metal-oxide clusters down to subnanometer scale.

In photodynamic therapy (PDT), light-sensitive photosensitizers produce reactive oxygen species (ROS) after irradiation in the presence of oxygen. Atomically-precise thiolate-protected gold nanoclusters are molecule-like nanostructures with discrete energy levels presenting long lifetimes, surface biofunctionality, and strong near-infrared excitation ideal for ROS generation in PDT. We directly compare thiolate-gold macromolecular complexes (Au10) and atomically-precise gold nanoclusters (Au25), and investigate the influence of ligands on their photoexcitation. With the ability of atomically-precise nanochemistry, we produce Au10SG10, Au10AcCys10, Au25SG18, and Au25AcCys18 (SG: glutathione; AcCys: N-acetyl-cysteine) fully characterized by high-resolution mass spectrometry. Our theoretical investigation reveals key factors (energetics of excited states and structural influence of surface ligands) and their relative importance in singlet oxygen formation upon one- and two-photon excitation. Finally, we explore ROS generation by gold nanoclusters in living cells with one- and two-photon excitation. Our study presents in-depth analyses of events within gold nanoclusters when photo-excited both in the linear and nonlinear optical regimes, and possible biological consequences in cells.

Nanometer-scaled objects are known to have dimension-related properties, but sometimes the assembly of such objects can lead to the emergence of other properties. Here, we show the assembly of atomically precise gold nanoclusters into large fibrillar structures that are featuring excitation-dependent luminescence with an excitation-selective circularly polarized luminescence (CPL), even though all components are achiral. The origin of CPL in the assembly of atomic clusters has been attributed to the hierarchical organization of atomic clusters into fibrillar structures, mediated via a hydrogen bonding interaction with a surfactant. We follow the assembly process both experimentally and computationally showing the advance in the structural formation along with its chiroptical electronic properties, i.e., circular dichroism (CD) and CPL. Our study here can assist in the rational design of materials featuring chiroptical properties, thus leading to a controlled CPL activity.

Luminescent gold nanoclusters are rapidly gaining attention as efficient theranostic targets for imaging and therapeutics. Indeed, their ease of synthesis, their tunable optical properties and tumor targeting make them potential candidates for sensitive diagnosis and efficacious therapeutic applications. This concept highlights the key components for designing gold nanoclusters as efficient theranostics focusing on application in the field of oncology.

Interfacing ultrasmall metal nanoclusters (NCs) with proteins can present a dual opportunity: proteins can be used for protecting NCs, and the surface ligands of NCs may interact with proteins. Here, the authors identify and discuss remaining open questions surrounding the bio-NC interface that call for future research efforts.

Noble metal nanoclusters allow for the atomically-precise control of their composition. However, to create nanoclusters with pre-defined optical properties, comprehensive description of their structure-property relation is required. Here, we report the gold atom doping impact on one-photon and two-photon absorption (TPA) and luminescence properties of ligated silver nanoclusters via combined experimental studies and time-dependent density functional theory simulations (TD-DFT). We synthesized a series of Ag25-x Aux (DMBT)18 nanoclusters where x=0, 1 and 5-10. For Ag24 Au1 (DMBT)18 we demonstrate that the presence of the central Au dopant strongly influences linear and non-linear optical properties, increasing photoluminescence quantum yield and two-photon brightness, with respect to undoped silver nanoclusters. With improved TPA and luminescence, atomically-precise AuAg alloys presented in our work can serve as robust luminescent probes e.g. for bioimaging in the second biological window.

The purpose of the current study is to uncover the impact of small liganded gold nanoclusters with 10 gold atoms and 10 glutathione ligands (Au10SG10) on several biomarkers in human microglia. We established the links connecting the atomically precise structure of Au10SG10 with their properties and changes in several biomolecules under oxidative stress. Au10SG10 caused the loss of mitochondrial metabolic activity, increased lipid peroxidation and translocation of an alarmin molecule, high mobility group box 1 (HMGB1), from the nucleus to the cytosol. Molecular modeling provided an insight into the location of amino acid interaction sites with Au10SG10 and the nature of bonds participating in these interactions. We show that Au10SG10 can bind directly to the defined sites of reduced, oxidized, and acetylated HMGB1. Further studies with similar complementary approaches merging live-cell analyses, determination of biomarkers, and cell functions could lead to optimized gold nanoclusters best suited for diagnostic and bioimaging purposes in neuroscience.

Atomically precise gold nanoclusters are a fascinating class of nanomaterials that exhibit molecule-like properties and have outstanding photoluminescence (PL). Their ultrasmall size, molecular chemistry, and biocompatibility make them extremely appealing for selective biomolecule labeling in investigations of biological mechanisms at the cellular and anatomical levels. In this work, we report a simple route to incorporate a preformed Au25 nanocluster into a model bovine serum albumin (BSA) protein. A new approach combining small-angle X-ray scattering and molecular modeling provides a clear localization of a single Au25 within the protein to a cysteine residue on the gold nanocluster surface. Attaching Au25 to BSA strikingly modifies the PL properties with enhancement and a redshift in the second near-infrared (NIR-II) window. This study paves the way to conrol the design of selective sensitive probes in biomolecules through a ligand-based strategy to enable the optical detection of biomolecules in a cellular environment by live imaging.

For very small nanocluster-based catalysts, the exploration of the influence of the particle size, composition, and support offers precisely variable parameters in a wide material search space to control catalysts’ performance. We present the mechanism of the CO2 methanation reaction on the oxidized bimetallic Cu3Pd tetramer (Cu3PdO2) supported on a zirconia model support represented by Zr12O24 based on the energy profile obtained from density functional theory calculations on the reaction of CO2 and H2. In order to determine the role of the Pd atom, the performance of Cu3PdO2 with monometallic Cu4O2 at the same support has been compared. Parallel to methane formation, the alternative path of methanol formation at this catalyst has also been investigated. The results show that the exchange of a single atom in Cu4 with a single Pd atom improves catalyst/s performance via lowering the barriers associated with hydrogen dissociation steps that occur on the Pd atom. The above-mentioned results suggest that the doping strategy at the level of single atoms can offer a precise control knob for designing new catalysts with desired performance.

Subnanometer copper tetramer-zirconia catalysts turn out to be highly efficient for CO2 hydrogenation and its conversion to methane. The cluster size and substrate morphology are controlled to optimize the catalytic performance. The two types of zirconia supports investigated are prepared by atomic layer deposition (similar to 3 nm thick film) and supersonic cluster beam deposition (nanostructured film, similar to 100 nm thick). The substrate plays a crucial role in determining the activity of the catalyst as well as its cyclability over repeated thermal ramps. A temperature-programmed reaction combined with in situ X-ray characterization reveals the correlation between the evolution in the oxidation state and catalytic activity. Ex situ photoelectron spectroscopy indicates Cu clusters with stronger interactions with the nanostructured film, which can be the cause for the higher activity of this catalyst. Density functional theory calculations based on the Cu4O2 cluster supported on a ZrOx subunit reveal low activation barriers and provide mechanism for CO2 hydrogenation and its conversion to methane. Altogether, the results show a new way to tune the catalytic activity of CO2 hydrogenation catalysts through controlling the morphology of the support at the nanoscale.

Ultra-small gold nanoclusters (AuNCs) with designed sizes and ligands are gaining popularity for biomedical purposes and ultimately for human imaging and therapeutic applications. Human non-tumor brain cells, astrocytes, are of particular interest because they are abundant and play a role in functional regulation of neurons under physiological and pathological conditions. Human primary astrocytes were treated with AuNCs of varying sizes (Au10, Au15, Au18, Au25) and ligand composition (glutathione, polyethylene glycol, N-acetyl cysteine). Concentration and time-dependent studies showed no significant cell loss with AuNC concentrations <10 μM. AuNC treatment caused marked differential astrocytic responses at the organellar and transcription factor level. The effects were exacerbated under severe oxidative stress induced by menadione. Size-dependent effects were most remarkable with the smallest and largest AuNCs (10, 15 Au atoms versus 25 Au atoms) and might be related to the accessibility of biological targets toward the AuNC core, as demonstrated by QM/MM simulations. In summary, these findings suggest that AuNCs are not inert in primary human astrocytes, and that their sizes play a critical role in modulation of organellar and redox-responsive transcription factor homeostasis.

Interleukin- 6 (IL-6) is involved in physiological and pathological processes. Different pharmacological agents have been developed to block IL-6 deleterious effects and to recover homeostatic IL-6 signaling. One of the proposed nanostructures in pre-clinical investigations which reduced IL-6 concentrations is polyglycerol dendrimer, a nano-structure with multiple sulfate groups. The aim of the present study was to uncover the type of binding between critical positions in the human IL-6 structure available for binding dPGS and compare it with heparin sulfate binding. We studied these interactions by performing docking simulations of dPGS and heparins with human IL-6 using AutoDock Vina. These molecular docking analyses indicate that the two ligands have comparable affinities for the positively charged positions on the surface of IL-6. All-atom molecular dynamics simulations (MD) employing Gromacs were used to explore the binding sites and binding strengths. Results suggest two major binding sites and show that the strengths of binding are similar for heparin and dPGS (−5.5–6.4 kcal/ mol). dPGS or its analogs could be used in the therapeutic intervention in sepsis and inflammatory disorders to reduce unbound IL-6 in the plasma or tissues and its binding to the receptors. We propose that analogs of dPGS could specifically block IL-6 binding in the desired signaling mode and would be valuable new probes to establish optimized therapeutic intervention in inflammation.