Molecular interpretation of pharmaceuticals' adsorption on carbon nanomaterials: Theory meets experiments

The ability of carbon-based nanomaterials (CNM) to interact with a variety of pharmaceutical drugs can be exploited in many applications. In particular, they have been studied both as carriers for in vivo drug delivery and as sorbents for the treatment of water polluted by pharmaceuticals. In recent years, the large number of experimental studies was also assisted by computational work as a tool to provide understanding at molecular level of structural and thermodynamic aspects of adsorption processes. Quantum mechanical methods, especially based on density functional theory (DFT) and classical molecular dynamics (MD) simulations were mainly applied to study adsorption/release of various drugs. This review aims to compare results obtained by theory and experiments, focusing on the adsorption of three classes of compounds: (i) simple organic model molecules; (ii) antimicrobials; (iii) cytostatics. Generally, a good agreement between experimental data (e.g. energies of adsorption, spectroscopic properties, adsorption isotherms, type of interactions, emerged from this review) and theoretical results can be reached, provided that a selection of the correct level of theory is performed. Computational studies are shown to be a valuable tool for investigating such systems and ultimately provide useful insights to guide CNMs materials development and design

Pt Nanoelectrodes Sealed in Quartz Capillaries Modified with Underpotential-Deposited Bismuth for Formic Acid Electrooxidation

Platinum disk nano- and micro-electrodes with radii in the range 40 nm-12.5 mu m were fabricated using quartz capillaries and the laser-puller assisted approach. The hydrogen underpotential deposition (H-UPD), performed in a 0.5 M H2SO4 aqueous solution, revealed that the nanoelectrodes, with radii of 160 nm and less, displayed extraordinarily large surface areas, which in terms of roughness factors (RFs, i. e., the ratio of the real surface areas to the geometric surface areas) were in the range 1030-3600. This finding was attributed to diffusion of adsorbed species at the Pt/quartz interface along portions of the Pt wires sealed within the glass. RFs between 2 and 3 were instead found at the microelectrodes. Similar results were also obtained with underpotential-deposited metallic bismuth. In this case, diffusion of Bi adatoms onto the Pt surface was hindered to some extent, providing a RF value of 172. Bi-modified Pt nano- and micro-electrodes were employed to study the electrooxidation of HCOOH, which is of interest in the field of fuel cells. It was found that the nanoelectrode displayed higher activity towards the electrooxidation of HCOOH and tolerance to CO poisoning, compared to the microelectrode

Intercalation Ability of Novel Monofunctional Platinum Anticancer Drugs: A Key Step in Their Biological Action

Phenanthriplatin (PtPPH) is a monovalent platinum(II)-based complex with a large cytotoxicity against cancer cells. Although the aqua-activated drug has been assumed to be the precursor for DNA damage, it is still under debate whether the way in which that metallodrug attacks to DNA is dominated by a direct binding to a guanine base or rather by an intercalated intermediate product. Aiming to capture the mechanism of action of PtPPH, the present contribution used theoretical tools to systematically assess the sequence of all possible mechanisms on drug activation and reactivity, for example, hydrolysis, intercalation, and covalent damage to DNA. Ab initio quantum mechanical (QM) methods, hybrid QM/QM\u2032 schemes, and independent gradient model approaches are implemented in an unbiased protocol. The performed simulations show that the cascade of reactions is articulated in three well-defined stages: (i) an early and fast intercalation of the complex between the DNA bases, (ii) a subsequent hydrolysis reaction that leads to the aqua-activated form, and (iii) a final formation of the covalent bond between PtPPH and DNA at a guanine site. The permanent damage to DNA is consequently driven by that latter bond to DNA but with a simultaneous \u3c0-\u3c0intercalation of the phenanthridine into nucleobases. The impact of the DNA sequence and the lateral backbone was also discussed to provide a more complete picture of the forces that anchor the drug into the double helix

Elusive Coordination of the Ag+Ion in Aqueous Solution: Evidence for a Linear Structure

X-ray absorption spectroscopy (XAS) has been employed to study the coordination of the Ag+ ion in aqueous solution. The conjunction of extended X-ray absorption fine structure (EXAFS) and X-ray absorption near-edge structure (XANES) data analysis provided results suggesting the preference for a first shell linear coordination with a mean Ag-O bond distance of 2.34(2) \uc5, different from the first generally accepted tetrahedral model with a longer mean Ag-O bond distance. Ab initio molecular dynamics simulations with the Car-Parrinello approach (CPMD) were also performed and were able to describe the coordination of the hydrated Ag+ ion in aqueous solution in very good agreement with the experimental data. The high sensitivity for the closest environment of the photoabsorber of the EXAFS and XANES techniques, together with the long-range information provided by CPMD and large-angle X-ray scattering (LAXS), allowed us to reconstruct the three-dimensional model of the coordination geometry around the Ag+ ion in aqueous solution. The obtained results from experiments and theoretical simulations provided a complex picture with a certain amount of water molecules with high configurational disorder at distances comprised between the first and second hydration spheres. This evidence may have caused the proliferation of the coordination numbers that have been proposed so far for Ag+ in water. Altogether these data show how the description of the hydration of the Ag+ ion in aqueous solution can be complex, differently from other metal species where hydration structures can be described by clusters with well-defined geometries. This diffuse hydration shell causes the Ag-O bond distance in the linear [Ag(H2O)2]+ ion to be ca. 0.2 \uc5 longer than in isolated ions in solid state

A glucose-based molecular rotor inhibitor of glycogen phosphorylase as a probe of cellular enzymatic function

Molecular rotors belong to a family of fluorescent compounds characterized as molecular switches, where a fluorescence on/off signal signifies a change in the molecule's microenvironment. Herein, the successful synthesis and detailed study of (E)-2-cyano-3-(p-(dimethylamino)phenyl)-N-(beta-D-glucopyranosyl)acrylam ide (RotA), is reported. RotA was found to be a strong inhibitor of rabbit muscle glycogen phosphorylase (RMGPb), that binds at the catalytic site of the enzyme. RotA's interactions with the residues lining the catalytic site of RMGPb were determined by X-ray crystallography. Spectroscopic studies coupled with theoretical calculations proved that RotA is a molecular rotor. When bound in the catalytic channel of RMGPb, it behaved as a light switch, generating a strong fluorescence signal, allowing utilization of RotA as a probe that locates glycogen phosphorylase (GP). RotA, mono-, di- and per-acetylated derivatives, as well as nanoparticles with RotA encapsulated in polyethylene glycol-poly-L-histidine, were used in live cell fluorescence microscopy imaging to test the delivery of RotA through the plasma membrane of HepG2 and A431 cells, with the nanoparticles providing the best results. Once in the intracellular milieu, RotA exhibits remarkable colocalization with GP and significant biological effects, both in cell growth and inhibition of GP