Anti-cancer effect of melittin-Au25(MHA)18 complexes on human cervical cancer HeLa cells

Garg

2023

ACS Appl. Bio Mater.

Monolayer-protected atomically precise metal nanoclusters (MPCs) have potential applications in catalysis, imaging, and drug delivery. Understanding their interactions with biomolecules such as peptides is of paramount interest for their use in cell imaging and drug delivery. Here we have carried out atomistic molecular dynamics simulations to investigate the interactions between MPCs and an anticancer peptide, melittin. Melittin gets attached to the MPCs surface by the formation of multiple hydrogen bonds between its amino acid residues with MPCs ligands. Additionally, the positively charged Lys, Arg, and peptide's N-terminal strongly anchor the peptide to the MPC metal surface, providing extra stabilization.

Section: Introductionmentioning

confidence: 99%

Insights into the Interactions of Peptides with Monolayer-Protected Metal Nanoclusters

Garg

2023

ACS Appl. Bio Mater.

“…27 Some recent reports have shown biological applications of water-dispersible MPCs including anticancer activity, 30 anti-Alzheimer's drug, 31 and as a delivery vehicle for an anticancer drug. 32,33 Recently some insights into the aggregation of MPCs and their interaction with the biological environment have been provided using experimental as well as computational methods at atomistic and coarse-grained levels. [34][35][36][37][38][39][40][41][42] Vanzan et al, studied the dimerization of three different Au 25 -based nanoclusters functionalized with hydrophobic ligands in dichloromethane solvent using metadynamics (MetaD)simulations.…”

Section: Introductionmentioning

confidence: 99%

Understanding Molecular Aggregation of Ligand-protected Atomically-Precise Metal Nanoclusters

2023

Preprint

Atomically precise ligand-protected nanoclusters (MPC) have emerged as an important class of molecules due to their unique structural features and diverse potential applications, including nano-electronics, bio-imaging, as sensors and drug carriers. Understanding the atomistic details of their intermolecular interaction is of paramount interest for designing, synthesizing, and system-specific applications. Crystal structures of various MPCs provide details related to molecular packing and intermolecular interactions. While these experiments reveal macroscopic, mostly static properties, they are often limited by the spatial and temporal resolutions in delineating the microscopic dynamical details. Here we apply molecular dynamics and enhanced sampling simulations to study the aggregation of Au25(pMBA)18 MPCs in the solution phase. The MPCs interact via both hydrogen bonds and π-stacks between the aromatic ligands to form stable dimers, oligomers, and periodic crystals. The free energy profiles obtained from enhanced sampling simulations of dimerization reveal a pivotal role of the protonated states of the ligands as well as the solvation shell in mediating the molecular aggregation process in solution. In the solid phase, the MPCs’ ligands have suppressed conformational flexibility owing to many facile intermolecular hydrogen bonds and π- stacks. Our work provides unprecedented molecular-level details of the aggregation process and conformational dynamics of MPCs ligands in the solution and crystalline phases, which will help rational design of new MPCs with specific properties.

“…Ever since its synthesis and characterization, its catalytic and physicochemical properties (such as optical and magnetic) have been explored in great detail. − Most of the Au 25 (SR) 18 nanoclusters studied until date contain water-insoluble ligands, whereas some water-soluble thiol-based ligands such as p -mercaptobenzoic acid ( p MBA), 11-mercaptoundecanoic acid (11-MUA), cysteine (Cys), captopril , (Capt), and glutathione , (GSH) have also been used to synthesize MPCs. Some recent reports have shown biological applications of water-dispersible MPCs, as anticancer agent, anti-Alzheimer’s drug, and as a delivery vehicle for drug molecules. , …”

mentioning

confidence: 99%

“…Some recent reports have shown biological applications of water-dispersible MPCs, as anticancer agent, 29 anti-Alzheimer's drug, 30 and as a delivery vehicle for drug molecules. 31,32 Recently some insights into the aggregation of MPCs and their interaction with the biological environment have been provided using experimental as well as computational methods at atomistic and coarse-grained levels. 33−44 Vanzan et al, studied the dimerization of three different Au 25 -based nanoclusters functionalized with hydrophobic ligands in dichloromethane solvent using metadynamics (MetaD) simulations.…”

mentioning

confidence: 99%

Understanding Molecular Aggregation of Ligand-Protected Atomically-Precise Metal Nanoclusters

2023

J. Phys. Chem. Lett.

Monolayer-protected atomically precise nanoclusters (MPCs) are an important class of molecules due to their unique structural features and diverse applications, including bioimaging, sensors, and drug carriers. Understanding the atomistic and dynamical details of their self-assembly process is crucial for designing system-specific applications. Here, we applied molecular dynamics and on-the-fly probability-based enhanced sampling simulations to study the aggregation of Au25(pMBA)18 MPCs in aqueous and methanol solutions. The MPCs interact via both hydrogen bonds and π-stacks between the aromatic ligands to form stable dimers, oligomers, and crystals. The dimerization free energy profiles reveal a pivotal role of the ligand charged state and solvent mediating the molecular aggregation. Furthermore, MPCs’ ligands exhibit suppressed conformational flexibility in the solid phase due to facile intercluster hydrogen bonds and π-stacks. Our work provides unprecedented molecular-level dynamical details of the aggregation process and conformational dynamics of MPCs ligands in solution and crystalline phases.