Vijay Reddy Jupally

Interstaple Dithiol Cross-Linking in Au25(SR)18 Nanomolecules: A Combined Mass Spectrometric and Computational Study

A systematic study of cross-linking chemistry of the Au(25)(SR)(18) nanomolecule by dithiols of varying chain length, HS-(CH(2))(n)-SH where n = 2, 3, 4, 5, and 6, is presented here. Monothiolated Au(25) has six [RSAuSRAuSR] staple motifs on its surface, and MALDI mass spectrometry data of the ligand exchanged clusters show that propane (C3) and butane (C4) dithiols have ideal chain lengths for interstaple cross-linking and that up to six C3 or C4 dithiols can be facilely exchanged onto the cluster surface. Propanedithiol predominately exchanges with two monothiols at a time, making cross-linking bridges, while butanedithiol can exchange with either one or two monothiols at a time. The extent of cross-linking can be controlled by the Au(25)(SR)(18) to dithiol ratio, the reaction time of ligand exchange, or the addition of a hydrophobic tail to the dithiol. MALDI MS suggests that during ethane (C2) dithiol exchange, two ethanedithiols become connected by a disulfide bond; this result is supported by density functional theory (DFT) prediction of the optimal chain length for the intrastaple coupling. Both optical absorption spectroscopy and DFT computations show that the electronic structure of the Au(25) nanomolecule retains its main features after exchange of up to eight monothiol ligands.

Core Size Conversion: Route for Exclusive Synthesis of Au38 or Au40 Nanomolecules

Gold nanomolecules with a precise number of gold atoms and ligands have promise for catalytic, optical, and biomedical applications. For practical applications, it is essential to develop synthetic protocols to prepare monodisperse gold nanomolecules. A typical synthesis yields a number of nanomolecules with discrete numbers of core atoms. Thermochemical treatment in the presence of excess thiol, etching, is known to narrow down the number of discrete nanomolecules, by selective degradation of sizes with lower stability. Au38(SR)24 and Au40(SR)24 are abundantly formed in these etching reactions due to their extraordinary stability to chemical etching. These nanomolecules are of high interest due in part to its stability, X-ray crystallographic structure availability (Au38), and intrinsic chirality arising from the arrangement of the Au-SR interface. However, the synthetic routes typically yield a mixture of Au38 and Au40, demanding extensive separation protocols. Here, we present a synthetic route to prepare either Au38 or Au40 exclusively in the product of etching. This was made possible by conducting a comprehensive mechanistic study starting from single-sized reactant. Au67 on etching yields Au40 exclusively. Au(103-105)(SR)(45-46) on etching also yields Au40 exclusively. Clusters of various sizes smaller than Au67 on etching yield Au38 exclusively. This is the first direct evidence for the exclusive formation of Au38 and Au40 nanomolecules by core size conversion. Mass spectrometry was used to study the core size conversion reactions to understand the mechanism. Au38 and Au40 nanomolecules form via different intermediates, as observed in the mass spectrometry data.

Transformation of Au144(SCH2CH2Ph)60 to Au133(SPh-tBu)52 Nanomolecules: Theoretical and Experimental Study

Ultrastable gold nanomolecule Au144(SCH2CH2Ph)60 upon etching with excess tert-butylbenzenethiol undergoes a core-size conversion and compositional change to form an entirely new core of Au133(SPh-tBu)52. This conversion was studied using high-resolution electrospray mass spectrometry which shows that the core size conversion is initiated after 22 ligand exchanges, suggesting a relatively high stability of the Au144(SCH2CH2Ph)38(SPh-tBu)22 intermediate. The Au144 → Au133 core size conversion is surprisingly different from the Au144 → Au99 core conversion reported in the case of thiophenol, -SPh. Theoretical analysis and ab initio molecular dynamics simulations show that rigid p-tBu groups play a crucial role by reducing the cluster structural freedom, and protecting the cluster from adsorption of exogenous and reactive species, thus rationalizing the kinetic factors that stabilize the Au133 core size. This 144-atom to 133-atom nanomolecules compositional change is reflected in optical spectroscopy and electrochemistry.

An analysis of the sponge Acanthostrongylophora igens' microbiome yields an actinomycete that produces the natural product manzamine A

Sponges have generated significant interest as a source of bioactive and elaborate secondary metabolites that hold promise for the development of novel therapeutics for the control of an array of human diseases. However, research and development of marine natural products can often be hampered by the difficulty associated with obtaining a stable and sustainable production source. Herein we report the first successful characterization and utilization of the microbiome of a marine invertebrate to identify a sustainable production source for an important natural product scaffold. Through molecular-microbial community analysis, optimization of fermentation conditions and MALDI-MS imaging, we provide the first report of a sponge-associated bacterium (Micromonospora sp.) that produces the manzamine class of antimalarials from the Indo-Pacific sponge Acanthostrongylophora ingens (Thiele, 1899) (Class Demospongiae, Order Haplosclerida, Family Petrosiidae). These findings suggest that a general strategy of analysis of the macroorganisms microbiome could significantly transform the field of natural products drug discovery by gaining access to not only novel drug leads, but the potential for sustainable production sources and biosynthetic genes at the same time.

Gold Thiolate Nanomolecules: Synthesis, Mass Spectrometry, and Characterization

This chapter summarizes the synthetic routes used for the following HS-CH2-CH2-Ph protected gold nanoclusters: Au25(SR)18, Au38(SR)24, Au40(SR)24, Au67(SR)35, Au103–105(SR)45–46, Au130(SR)50, and Au144(SR)60. The synthetic routes are based on either (a) direct synthetic route or (b) a core-size conversion route. The synthetic routes leading to the most stable clusters are discussed and the characterizational techniques used to study the products are described.