Hydrogen/deuterium exchange mass spectrometry was employed to probe the conformational changes in lysozyme (Lyz) during the course of formation of a protein-protected atomically precise Au8 cluster. MALDI MS showed the protein, Lyz, to be present in a denatured state in the cluster. Detailed ESI MS analysis of the Au-attached Lyz adducts, an intermediate of cluster formation, confirmed that these conformational changes are brought about by Au-S bond formation and a similar conformation is retained in the final cluster. These results were supported by computational results, which showed an increase in solvent accessible surface area upon the formation of the adducts. Infrared spectroscopy established that change in the rate as well as the extent of the hydrogen/deuterium exchange observed in the cluster was due to the change in the amide II region of the encapsulating protein. Hydrogen/deuterium exchange ESI MS of Cu adducts of Lyz showed a lower degree of denaturation than their Au counterparts. XPS analysis revealed that Cu binds differently to Lyz than it does with Au, which is likely because of the stronger soft-soft Au-S interaction. Alkali metal ion binding, on the other hand, does not affect the protein conformation because such ions do not affect the disulfide bonds. © 2019 American Chemical Society.

Pradeep Thalappil

Department Of Chemistry

Debasmita Ghosh

Md Rabiul Islam

Alkali metals

Amides

Copper

Covalent bonds

Hydrogen

infrared spectroscopy

Mass spectrometry

Metal ions

Precious metals

Proteins

SULFUR COMPOUNDS

CLUSTER FORMATIONS

Computational results

Conformational change

Disulfide bonds

HYDROGEN/DEUTERIUM EXCHANGE

NOBLE METAL CLUSTERS

protein conformation

SOLVENT ACCESSIBLE SURFACE AREAS

Gold compounds

IIT Madras is a public technical and research university located in Chennai, Tamil Nadu. Founded in 1959, it is recognised as an Institute of National Importance.

IIT Madras has been ranked as the top engineering institute in India for four years in a row by the National Institutional Ranking Framework of the MHRD

It currently offers undergraduate, postgraduate and research degrees across 16 disciplines in Engineering, Sciences, Humanities and Management. About 596 faculty belonging to science and engineering departments and centres of the Institute are engaged in teaching, research and industrial consultancy.

IIT Madras

Journal of Physical Chemistry C

A new synthetic protocol is introduced which preserves the secondary structure of protecting proteins encapsulating a luminescent atomically-precise silver cluster. This was achieved by using a preformed triphenylphosphine (TPP)-protected silver cluster as the precursor forming bovine serum albumin (BSA)- and human serum albumin (HSA)-protected Ag18 clusters. This is the first example of the formation of luminescent protein-protected clusters in a neutral medium, without using any reducing agent, which results in minimal alteration of the protein structure during cluster growth. The cluster formed showed exceptional stability, unlike other silver clusters of this class. The formation of these red luminescent clusters was visualized by UV-vis and photoluminescence spectroscopy. The identification of Ag18 core was made through matrix-assisted laser desorption ionization mass spectrometry (MALDI MS), and a plausible mechanism of the formation was identified by monitoring the systematic growth of the cluster core by time-dependent MALDI MS experiments and electrospray ionization mass spectrometry (ESI MS) of the reaction mixture. The cluster was successfully employed as a luminescent probe for cancer cell imaging. Retention of protein conformation in the clusters was confirmed through circular dichroism (CD) spectroscopy, and the same was reflected in the retention of 89% of the esterase activity of BSA in the Ag18@BSA clusters synthesized by this method, compared to only 28.7% for AgQC@BSA clusters synthesized using previous protocols, conducted in basic medium. © 2019 American Chemical Society.

Internalization of a Preformed Atomically Precise Silver Cluster in Proteins by Multistep Events and Emergence of Luminescent Counterparts Retaining Bioactivity

Ion mobility mass spectrometry studies on Aun-Lyz adducts showed gradual unfolding of the protein structure during binding of Au+ to the protein. The change of the charge state envelope in Aun-Lyz from that of Lyz in ESI MS data confirmed the relaxation of the protein structure. This Au+ binding occurs at cysteine sites through the breakage of disulfide bonds and this ruptures the H-bonded folded network structure of the protein leading to ∼30% change in helicity. Nearly 15% loss in the total H-bonding occurred during the attachment of 8 Au to the protein as calculated by a molecular dynamics simulation. Different Aun-Lyz structures were simulated, which confirmed significant unfolding of the protein. The structural insights were used to understand similar unfolding in the solution state as seen via circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. This open structure is indeed necessary to accommodate a cluster core inside a protein cavity during luminescent cluster synthesis. These studies unambiguously establish noble metal binding-induced conformational changes of protein structures to accommodate the clusters. © 2017 American Chemical Society.

Gold-Induced Unfolding of Lysozyme: Toward the Formation of Luminescent Clusters

Atomically precise pieces of matter of nanometer dimensions composed of noble metals are new categories of materials with many unusual properties. Over 100 molecules of this kind with formulas such as Au25(SR)18, Au38(SR)24, and Au102(SR)44 as well as Ag25(SR)18, Ag29(S2R)12, and Ag44(SR)30 (often with a few counterions to compensate charges) are known now. They can be made reproducibly with robust synthetic protocols, resulting in colored solutions, yielding powders or diffractable crystals. They are distinctly different from nanoparticles in their spectroscopic properties such as optical absorption and emission, showing well-defined features, just like molecules. They show isotopically resolved molecular ion peaks in mass spectra and provide diverse information when examined through multiple instrumental methods. Most important of these properties is luminescence, often in the visible-near-infrared window, useful in biological applications. Luminescence in the visible region, especially by clusters protected with proteins, with a large Stokes shift, has been used for various sensing applications, down to a few tens of molecules/ions, in air and water. Catalytic properties of clusters, especially oxidation of organic substrates, have been examined. Materials science of these systems presents numerous possibilities and is fast evolving. Computational insights have given reasons for their stability and unusual properties. The molecular nature of these materials is unequivocally manifested in a few recent studies such as intercluster reactions forming precise clusters. These systems manifest properties of the core, of the ligand shell, as well as that of the integrated system. They are better described as protected molecules or aspicules, where aspis means shield and cules refers to molecules, implying that they are "shielded molecules". In order to understand their diverse properties, a nomenclature has been introduced with which it is possible to draw their structures with positional labels on paper, with some training. Research in this area is captured here, based on the publications available up to December 2016. © 2017 American Chemical Society.

Chemical Reviews

Atomically Precise Clusters of Noble Metals: Emerging Link between Atoms and Nanoparticles

Structure-reactivity correlations in metal atom substitution reactions of three model monolayer-protected alloy clusters, Ag25-xAux(SR)18 (I), Au25-xAgx(SR)18 (II), and AuxAg44-x(SR)30 (III) where (-SR = alkyl/arylthiolate), are demonstrated. We show that the Au atoms of I and III and Ag atoms of II can be substituted by their reactions with the parent clusters Ag25(SR)18, Ag44(SR)30, and Au25(SR)18, respectively. Though these alloy clusters possess certain common structural features, they exhibit distinctly different reactivities in these substitution reactions. The Au of I and III and Ag of II at the outermost sites, i.e., M2(SR)3 staples of I and II and M2(SR)5 mounts of III, were substituted more easily compared to those at the inner, icosahedral sites. Au atoms at the icosahedral shell of I were completely substituted while Ag atoms of II at similar positions were not labile for substitution. This shows that the icosahedral shell of II is more rigid compared to that in I. We show that the Au atom in Ag24Au1(SR)18 cannot be substituted, which indicates that this Au atom is located at the center of the icosahedral shell. Similarly, when x ≤ 12, the Au atoms of III cannot be substituted, indicating that these atoms are located in the innermost icosahedral shell. In summary, our results demonstrate that metal atom substitution reactions correlate with the geometric structures of these clusters. © 2017 American Chemical Society.

Structure-Reactivity Correlations in Metal Atom Substitutions of Monolayer-Protected Noble Metal Alloy Clusters

We present the first example of intercluster reactions between atomically precise, monolayer protected noble metal clusters using Au25(SR)18 and Ag44(SR)30 (RS- = alkyl/aryl thiolate) as model compounds. These clusters undergo spontaneous reaction in solution at ambient conditions. Mass spectrometric measurements both by electrospray ionization and matrix assisted laser desorption ionization show that the reaction occurs through the exchange of metal atoms and protecting ligands of the clusters. Intercluster alloying is demonstrated to be a much more facile method for heteroatom doping into Au25(SR)18, as observed by doping up to 20 Ag atoms. We investigated the thermodynamic feasibility of the reaction using DFT calculations and a tentative mechanism has been presented. Metal core-thiolate interfaces in these clusters play a crucial role in inducing these reactions and also affect rates of these reactions. We hope that our work will help accelerate activities in this area to establish chemistry of monolayer protected clusters. © 2015 American Chemical Society.

Journal of the American Chemical Society

Intercluster Reactions between Au25(SR)18 and Ag44(SR)30

Ambient, structure-and topology-preserving chemical reactions between two archetypal nanoparticles, Ag 25 (SR) 18 and Au 25 (SR) 18, are presented. Despite their geometric robustness and electronic stability, reactions between them in solution produce alloys, Agm Aun (SR)18 (m+n=25), keeping their M25 (SR)18 composition, structure and topology intact. We demonstrate that a mixture of Ag25 (SR)18 and Au25 (SR)18 can be transformed to any arbitrary alloy composition, Agm Aun (SR)18 (n=1-24), merely by controlling the reactant compositions. We capture one of the earliest events of the process, namely the formation of the dianionic adduct, (Ag25 Au25 (SR)36) 2-, by electrospray ionization mass spectrometry. Molecular docking simulations and density functional theory (DFT) calculations also suggest that metal atom exchanges occur through the formation of an adduct between the two clusters. DFT calculations further confirm that metal atom exchanges are thermodynamically feasible. Such isomorphous transformations between nanoparticles imply that microscopic pieces of matter can be transformed completely to chemically different entities, preserving their structures, at least in the nanometric regime. © 2016 The Author(s).

Fulltext

Nature Communications

Structure-conserving spontaneous transformations between nanoparticles

Conformational Changes of Protein upon Encapsulation of Noble Metal Clusters: An Investigation by Hydrogen/Deuterium Exchange Mass Spectrometry

Journal	Data powered by TypesetJournal of Physical Chemistry C
Publisher	Data powered by TypesetAmerican Chemical Society
ISSN	19327447
Open Access	No