Asymmetric conformation of the high-spin state of iron(II)-tris(2,2-bipyridine): Time-resolved x-ray absorption and ultraviolet circular dichroism.

We analyze the structures of the low-spin (LS) ground state and the high-spin (HS) lowest excited state of the iron-(II)-tris bipyridine complex ([Fe(bpy)]) using density functional theory PBE methods, modeling the solvent interactions with conductor-like polarizable continuum model. These calculations are globally benchmarked against a wide range of experimental observables that include ultraviolet-visible linear absorption and circular dichroism (CD) spectra and Fe K-edge x-ray absorption near edge spectra (XANES). The calculations confirm the already established D geometry of the LS state, as well as a departure from this geometry for the HS state, with the appearance of inequivalent Fe-N bond elongations.

DFT Computational Analysis of the Mechanism of Action of Ru(II) Polypyridyl Complexes as Photoactivated Chemotherapy Agents: From Photoinduced Ligand Solvolysis to DNA Binding.

Photoactivated chemotherapy (PACT) is a form of target-oriented cancer therapy that exploits light of the proper wavelength to selectively activate the drug. Among the prodrugs used for this purpose, ruthenium-based complexes are particularly interesting, as when irradiated by light, they can release ligands by forming aquo-complexes able to bind DNA in both single and double strand fashions, causing its distortion. Using as model system a Ru(II) polypyridyl complex that has been demonstrated to be a promising photochemotherapeutic agent, all of the key aspects of the photoinduced solvolysis process and subsequent DNA interaction have been scrutinized using density functional theory (DFT) and time-dependent-DFT (TDDFT).

On the supramolecular interactions into a pH- and Metal-Actuated Molecular Shuttle: some insights from QTAIM modeling.

Supramolecular contacts responsible for chemical interaction of cucurbit[7]uril (CB[7]) macrocycle on a Tolyl-Viologen-Phenylene-Imidazole (T-VPI) molecular thread, at acid pH (T-VPI-H) or after Ag cation addition (T-VPI-Ag), are analytically addressed in a computational framework combining Quantum Theory of Atoms in Molecules (QTAIM) with Density Functional Theory (DFT). In this respect, the crystallographic structure (CCDC number 2217466) is taken as reference condition for addressing the nature of the chemical interactions driving the shuttling of the CB[7] between T and P stations recently observed in dilute water solutions. Beside the host(CB[7]) vs guest(T-VPI-H or T-VPI-Ag) complexation, the coordination sphere of the Ag cation is also investigated by means of local electronic energy density - H(r) - descriptors.

Optical and Supramolecular Properties of Cyclometalated Palladium Nanostructures with Tumor Targeting Properties in Living Mice: A Quantum Mechanics Interpretation.

The recent discovery that metallophilic interactions between cyclometalated palladium supramolecular nanostructures - with efficient tumour accumulation rate in a skin melanoma model - maintain excellent photodynamic properties even in a hypoxic microenvironment has inspired the present study focused on the theoretical predictions of optical properties of the bis-cyclometalated palladium compound in different contexts. More specifically, structural and UV/Vis absorption properties of both monomeric and dimeric forms of this anticancer drug are well reproduced with a Time-Dependent Density Functional Theoretical (TD-DFT) approach based on Exchange-Correlation (XC) hybrid functionals in conjunction with conductor-like and polarization solvation effects. A further novelty is represented by a fine investigation of the supramolecular interactions between the different subunits of the drug via dispersion force correction and Quantum Theory of Atoms in Molecules (QTAIM).

Noble Gas Anions: An Overview of Strategies and Bonding Motifs.

This review article aims to provide an overview of the strategies employed to prepare noble gas anions under different environments and experimental conditions, and of the bonding motifs typically occurring in these species. Observed systems include anions fixed into synthesized salts, detected in the gas phase or in high-pressure devices. The major role of the theoretical calculations is also highlighted, not only in support of the experiments, but also as effective in predicting still unreported species.

Noble gas hydrides: theoretical prediction of the first group of anionic species.

The first group of anionic noble-gas hydrides with the general formula HNgBeO (Ng = Ar, Kr, Xe, Rn) is predicted through MP2, Coupled-Cluster, and Density Functional Theory computations employing correlation-consistent atomic basis sets. We derive that these species are stable with respect to the loss of H, H, BeO, and BeO, but unstable with respect to Ng + HBeO. The energy barriers of the latter process are, however, high enough to suggest the conceivable existence of the heaviest HNgBeO species as metastable in nature.

G-quadruplex DNA selective targeting for anticancer therapy: a computational study of a novel Pt monofunctional complex activated by adaptive binding.

Targeting of G-quadruplex (G-Q) nucleic acids, which are helical four-stranded structures formed from guanine-rich nucleic acid sequences, has emerged in recent years as an appealing opportunity for drug intervention in anticancer therapy. Small-molecule drugs can stabilize quadruplex structures, promoting selective downregulation of gene expression and telomerase inhibition and also activating DNA damage responses. Thus, rational design of small molecular ligands able to selectively interact with and stabilize G-Q structures is a promising strategy for developing potent anti-cancer drugs with selective toxicity towards cancer cells over normal ones.

How Computations Can Assist the Rational Design of Drugs for Photodynamic Therapy: Photosensitizing Activity Assessment of a Ru(II)-BODIPY Assembly.

Ruthenium-based complexes represent a new frontier in light-mediated therapeutic strategies against cancer. Here, a density functional-theory-based computational investigation, of the photophysical properties of a conjugate BODIPY-Ru(II) complex, is presented. Such a complex was reported to be a good photosensitizer for photodynamic therapy (PDT), successfully integrating the qualities of a NIR-absorbing distyryl-BODIPY dye and a PDT-active [Ru(bpy)] moiety.

Computational Exploration of the Synergistic Anticancer Effect of a Multi-Action Ru(II)-Pt(IV) Conjugate.

An in-depth computational study of the ability of a recently proposed multi-action Ru(II)-Pt(IV) conjugate to act as a photosensitizer in photodynamic therapy (PDT) and chemotherapeutic drugs is presented here. The investigated complex is characterized by a polypyridyl Ru(II) chromophore linked to a Pt(IV) complex that, acting as a prodrug, should be activated by reduction releasing the Ru-based chromophore that can absorb light of proper wavelength to be used in PDT. The reaction mechanism for active species formation has been fully elucidated by means of density functional theory and its time-dependent extension.

Noble Gas-Silicon Cations: Theoretical Insights into the Nature of the Bond.

The structure, stability, and bonding situation of some exemplary noble gas-silicon cations were investigated at the MP2/aVTZ level of theory. The explored species include the mono-coordinated NgSiX3+ (Ng = He-Rn; X = H, F, Cl) and NgSiF22+ (Ng = He-Rn), the di-coordinated Ar2SiX3+ (X = H, F, Cl), and the “inserted” FNgSiF2+ (Ng = Kr, Xe, Rn). The bonding analysis was accomplished by the method that we recently proposed to assay the bonding situation of noblegas compounds.

Noble-gas compounds: A general procedure of bonding analysis.

This paper accounts for a general procedure of bonding analysis that is, expectedly, adequate to describe any type of interaction involving the noble-gas (Ng) atoms. Building on our recently proposed classification of the Ng-X bonds (X = binding partner) [New J. Chem.

Concerning the Role of -Hole in Non-Covalent Interactions: Insights from the Study of the Complexes of ArBeO with Simple Ligands.

The structure, stability, and bonding character of some exemplary Ar and -ArBeO ( = He, Ne, Ar, N, CO, F, Cl, ClF, HF, HCl, NH) were investigated by MP2 and coupled-cluster calculations, and by symmetry-adapted perturbation theory. The nature of the stabilizing interactions was also assayed by the method recently proposed by the authors to classify the chemical bonds in noble-gas compounds. The comparative analysis of the Ar and -ArBeO unraveled geometric and bonding effects peculiarly related to the -hole at the Ar atom of ArBeO, including the major stabilizing/destabilizing role of the electrostatic interactionensuing from the negative/positive molecular electrostatic potential of at the contact zone with ArBeO.

Altered Local Interactions and Long-Range Communications in UK Variant (B.1.1.7) Spike Glycoprotein.

The COVID-19 pandemic is caused by SARS-CoV-2. Currently, most of the research efforts towards the development of vaccines and antibodies against SARS-CoV-2 were mainly focused on the spike (S) protein, which mediates virus entry into the host cell by binding to ACE2. As the virus SARS-CoV-2 continues to spread globally, variants have emerged, characterized by multiple mutations of the S glycoprotein.

On the Proton-Bound Noble Gas Dimers (Ng-H-Ng) and (Ng-H-Ng') (Ng, Ng'= He-Xe): Relationships betweenStructure, Stability, and Bonding Character.

The structure, stability, and bonding character of fifteen (Ng-H-Ng) and (Ng-H-Ng') (Ng, Ng' = He-Xe) compounds were explored by theoretical calculations performed at the coupled cluster level of theory. The nature of the stabilizing interactions was, in particular, assayed using a method recently proposed by the authors to classify the chemical bonds involving the noble-gas atoms. The bond distances and dissociation energies of the investigated ions fall in rather large intervals, and follow regular periodic trends, clearly referable to the difference between the proton affinity (PA) of the various Ng and Ng'.

Complexes of helium with neutral molecules: Progress toward a quantitative scale of bonding character.

The complexes of helium with nearly 30 neutral molecules (M) were investigated by various techniques of bonding analysis and symmetry-adapted perturbation theory (SAPT). The main investigated function was the local electron energy density H(r), analyzed, in particular, so to estimate the degree of polarization (DoP) of He in the various He(M). As we showed recently (Borocci et al.

Noncovalent Complexes of the Noble-Gas Atoms: Analyzing the Transition from Physical to Chemical Interactions.

The bonding character of the noncovalent complexes of the noble-gas (Ng) atoms ranges from nearly purely dispersive contacts to interactions featuring appreciable contributions of induction and charge transfer. In this study, we discuss a new quantitative index that seems peculiarly informative about these diverse bonding situations. This index was termed as the degree of polarization (DoP) of Ng, as it measures, in essence, the Ng polarization promoted by the binding partner.

Dynamic multiple-scattering treatment of X-ray absorption: Parameterization of a new molecular dynamics force field for myoglobin.

We present a detailed analysis of the X-ray absorption near-edge structure (XANES) data on the Fe K-edge of CO Myoglobin based on a combined procedure of Molecular Dynamics (MD) calculations and MXAN (Minuit XANes) data analysis that we call D-MXAN. The ability of performing quantitative XANES data analysis allows us to refine classical force field MD parameters, thus obtaining a reliable tool for the atomic investigation of this important model system for biological macromolecules. The iterative procedure here applied corrects the greatest part of the structural discrepancy between classical MD sampling and experimental determinations.

Solvent dependency of the UV-Vis spectrum of indenoisoquinolines: role of keto-oxygens as polarity interaction probes.

Indenoisoquinolines are the most promising non-campthotecins topoisomerase IB inhibitors. We present an integrated experimental/computational investigation of the UV-Vis spectra of the IQNs parental compound (NSC314622) and two of its derivatives (NSC724998 and NSC725776) currently undergoing Phase I clinical trials. In all the three compounds a similar dependence of the relative absorption intensities at 270 nm and 290 nm on solvent polarity is found.

WEP: a high-performance analysis pipeline for whole-exome data.

Background: The advent of massively parallel sequencing technologies (Next Generation Sequencing, NGS) profoundly modified the landscape of human genetics.In particular, Whole Exome Sequencing (WES) is the NGS branch that focuses on the exonic regions of the eukaryotic genomes; exomes are ideal to help us understanding high-penetrance allelic variation and its relationship to phenotype. A complete WES analysis involves several steps which need to be suitably designed and arranged into an efficient pipeline.

Oxygen adsorption on β-quartz model surfaces: some insights from density functional theory calculations and semiclassical time-dependent dynamics.

The O/β-quartz interaction is described by combining our time-dependent semiclassical approach to atom-molecule/surface scattering with first-principles electronic structure calculations at the DFT (PBE0) level of accuracy. In particular, the O, O(2) interaction potentials with an on-top Si atom and its nearest O atom both localized over three different silica clusters have been calculated as a function of the oxygen-silica approaching distance. The calculated DFT potential energy surface has been used in semiclassical trajectory calculations to investigate the sticking and inelastic reflection of oxygen atoms from a model β-quartz surface.

Conformational analysis and UV/Vis spectroscopic properties of a rotaxane-based molecular machine in acetonitrile dilute solution: when simulations meet experiments.

A reduced form of a synthetic hydrogen-assembled molecular shuttle for nano-technological applications has been investigated by molecular dynamics simulations and density functional theory calculations. It is composed by a benzylic amide macrocycle mechanically locked onto a thread in acetonitrile solution. Classical sampling indicates, in agreement with experimental findings, that in equilibrium condition at 298 K the macrocycle and the naphthalimide radical anion moiety within the thread strongly interact forming four strong OCN-H-O=CNR hydrogen bonds.

Assignment of UV-vis spectrum of (3,3')-diindolylmethane, a Leishmania donovani topoisomerase IB inhibitor and a candidate DNA minor groove binder.

The geometrical optimization of (3,3')-diindolylmethane (DIM), an inhibitor of the bisubunit enzyme topoisomerase I from Leishmania donovani, a pathogenic protozoan parasite, mostly diffused in developing countries, has been carried out through quantum mechanical calculation. Using first-principle DFT restrained geometrical optimization, a potential energy surface has been constructed to identify a set of local minimum energy conformations of DIM. Starting from these conformations, the experimental UV-vis absorption spectrum in aqueous solution has been reproduced through TD-DFT calculations.

Structural and dynamical effects induced by the anticancer drug topotecan on the human topoisomerase I - DNA complex.

Background: Human topoisomerase I catalyzes the relaxation of DNA supercoils in fundamental cell processes like transcription, replication and chromosomal segregation. It is the only target of the camptothecin family of anticancer drugs. Among these, topotecan has been used to treat lung and ovarian carcinoma for several years.

Solvent effects on the valence UV-vis absorption spectra of topotecan anticancer drug in aqueous solution at room temperature: a nanoseconds time-scale TD-DFT/MD computational study.

The low-lying valence electronic excitations of the topotecan anticancer drug, in two stable lactone forms, have been addressed in infinite dilute aqueous solution by combining time-dependent density functional theory calculations with nanoseconds time-scale classical molecular dynamics simulations at 298 K. The effects of the surrounding and fluctuating classical environment on the investigated topotecan forms are included in a perturbed electronic Hamiltonian, which is computed, and then diagonalized, at each frame stored during the molecular dynamics sampling in explicit solution. Current results clearly indicate that, at moderately acidic and physiological conditions, the valence UV-vis absorption spectra of topotecan drug are strongly affected by the surrounding dielectric media and by its perturbing trajectory as arising from finite-temperature fluctuations and supramolecular interactions.