Inorganic anion recognition in aqueous solution by coupling nearby highly hydrophilic and hydrophobic moieties in a macrocyclic receptor.

Receptor L, composed of a tripropylenetetramine chain linking the 2 and 7 positions of an acridine unit methylene bridges, behaves as a pentaprotic base in aqueous solution. The first four protonation steps occur on the tetra-amine chain, while the acridine nitrogen protonates only below pH 4. The penta-protonated receptor assumes a folded conformation, resulting in a cleft delimited by the aliphatic tetramine and acridine moieties, in which anions of appropriate size can be hosted.

Cu(Proline) Complex: A Model of Bio-Copper Structural Ambivalence.

Complexes of Cu(d) with proline may be considered a simple model to address the structural flexibility and electronic properties of copper metalloproteins. To discuss optical electronic spectra and infrared spectral responses, we use quantum chemistry applied to model systems prepared under different geometries and degree of hydration. A comparison of experimental data with calculations indicates that first explicit neighbor water clustering next to the Cu(d) complex is critical for a correct description of the electronic properties of this system.

Ethanol electro-oxidation reaction on the Pd(111) surface in alkaline media: insights from quantum and molecular mechanics.

The ethanol electro-oxidation catalyzed by Pd in an alkaline environment involves several intermediate reaction steps promoted by the hydroxyl radical, OH. In this work, we report on the dynamical paths of the first step of this oxidation reaction, namely the hydrogen atom abstraction CHCHOH + OH → CHCHOH + HO, occurring at the Pd(111) surface and address the thermodynamic stability of the adsorbed reactants by means of quantum and molecular mechanics calculations, with special focus on the effect of the solvent. We have found that the impact of the solvent is significant for both ethanol and OH, contributing to a decrease in their adsorption free energies by a few dozen kcal mol with respect to the adsorption energy under vacuum.

Computational Investigation of the Selective Cleavage of Diastereotopic Cyclopropane Bonds in 5-Spirocyclopropane Isoxazolidines Rearrangement.

The complete path of the Brandi-Guarna rearrangement of 5-spirocyclopropane isoxazolidines has been investigated by means of density functional theory calculations to rationalize the competing formation of tetrahydropyridones and enaminones by the determination of the minimum energy reaction paths. Our calculations confirm that the rearrangement is triggered by the homolysis of the isoxazolidine N-O bond followed by cleavage of one of the two C-CH cyclopropane bonds as previously proposed by the Fabian group [ Eur. J.

Imidazole in Aqueous Solution: Hydrogen Bond Interactions and Structural Reorganization with Concentration.

The structural and dynamic properties of imidazole in aqueous solution have been studied by means of classical and ab initio molecular dynamics simulations. We developed a new force field for the imidazole molecule with improved modeling of the electrostatic interactions, specifically tailored to address the well-known drawbacks of existing force fields based on the atomic fractional charge approach. To this end, we reparametrized the charge distribution on the heterocyclic ring, introducing an extra site accounting for the lone pair on the deprotonated nitrogen.

A Photochromic Azobenzene Peptidomimetic of a β-Turn Model Peptide Structure as a Conformational Switch.

The insertion of azobenzene moiety in complex molecular protein or peptide systems can lead to molecular switches to be used to determine kinetics of folding/unfolding properties of secondary structures, such as α-helix, β-turn, or β-hairpin. In fact, in azobenzene, absorption of light induces a reversible trans ↔ cis isomerization, which in turns generates a strain or a structure relaxation in the chain that causes peptide folding/unfolding. In particular azobenzene may permit reversible conformational control of hairpin formation.

Correspondence between light-absorption spectrum and nonequilibrium work distribution as a mean to access free energy differences between electronic states.

The problem of recovering the free energy difference between two electronic states has been investigated by Frezzato [Chem. Phys. Lett.

Structural Insights into the Osteopontin-Aptamer Complex by Molecular Dynamics Simulations.

Osteopontin is an intrinsically disordered protein involved in tissue remodeling. As a biomarker for pathological hypertrophy and fibrosis, the protein is targeted by an RNA aptamer. In this work, we model the interactions between osteopontin and its aptamer, including mono- (Na) and divalent (Mg) cations.

Binding Free Energies of Host-Guest Systems by Nonequilibrium Alchemical Simulations with Constrained Dynamics: Illustrative Calculations and Numerical Validation.

In the companion article (Giovannelli et al., 10.1021/acs.

Insights on the Realgar Crystal Under Pressure from XP-PCM and Periodic Model Calculations.

The spectroscopic properties of AsS with pressure have been computed by the quantum mechanical XP-PCM method and by density functional theory periodic calculations. The comparison has allowed the interpretation of the available experimental data. By comparison of the two methods and with experiments, we show that the XP-PCM method is able to reproduce the same behavior of the periodic calculations with much lower computational cost allowing to be adopted as a first choice computational tool for a qualitative interpretation of molecular crystals properties under pressure.

Binding Free Energies of Host-Guest Systems by Nonequilibrium Alchemical Simulations with Constrained Dynamics: Theoretical Framework.

The fast-switching decoupling method is a powerful nonequilibrium technique to compute absolute binding free energies of ligand-receptor complexes (Sandberg et al., J. Chem.

Photochemical Reactivity of 1,6-Methano[10]annulene.

1,6-Methano[10]annulene solutions in cyclohexane have been subjected to continuous and pulsed UV irradiation. Photolysis occurs in both cases, giving naphthalene as a minor and major product, respectively. The wavelength dependence of the reaction in solution indicates that the photochemical process occurs, exciting 1,6-methano[10]annulene in the second and third singlet electronic excited states.

Statistical Mechanics of Ligand-Receptor Noncovalent Association, Revisited: Binding Site and Standard State Volumes in Modern Alchemical Theories.

The present paper is intended to be a comprehensive assessment and rationalization, from a statistical mechanics perspective, of existing alchemical theories for binding free energy calculations of ligand-receptor systems. In detail, the statistical mechanics foundation of noncovalent interactions in ligand-receptor systems is revisited, providing a unifying treatment that encompasses the most important variants in the alchemical approaches from the seminal double annihilation method [ Jorgensen et al. J.

II. Dissociation free energies in drug-receptor systems via nonequilibrium alchemical simulations: application to the FK506-related immunophilin ligands.

The recently proposed fast switching double annihilation (FS-DAM) [Cardelli et al., J. Chem.

Elastic Barrier Dynamical Freezing in Free Energy Calculations: A Way To Speed Up Nonequilibrium Molecular Dynamics Simulations by Orders of Magnitude.

An important issue concerning computer simulations addressed to free energy estimates via nonequilibrium work theorems, such as the Jarzynski equality [Phys. Rev. Lett.

Nonequilibrium Candidate Monte Carlo Simulations with Configurational Freezing Schemes.

Nonequilibrium Candidate Monte Carlo simulation [Nilmeier et al., Proc. Natl.

Computing Free Energy Differences of Configurational Basins.

A simulation-based approach is proposed to estimate free energy differences between configurational states A and B, defined in terms of collective coordinates of the molecular system. The computational protocol is organized into three stages that can be carried on simultaneously. Two of them consist of independent simulations aimed at sampling, in turn, A and B states.

Simulations in generalized ensembles through noninstantaneous switches.

Generalized-ensemble simulations, such as replica exchange and serial generalized-ensemble methods, are powerful simulation tools to enhance sampling of free energy landscapes in systems with high energy barriers. In these methods, sampling is enhanced through instantaneous transitions of replicas, i.e.

A fluorescent receptor for halide recognition: clues for the design of anion chemosensors.

The chemosensing properties of the polyaza-macrocycle 1-(6,7)-acridine-3,6,9,12-tetraaza-tridecaphane have been investigated by means of emission fluorescence spectroscopy, considering halide ions as substrates. As in the case of the free ligand, the fluorescence emission of the complexes is due to the acridinium species which are formed after photoinduced proton transfer reaction. The complexation constants have been obtained for the bi- and tri-protonated ligands in deoxygenated aqueous solutions.

Annealed importance sampling with constant cooling rate.

Annealed importance sampling is a simulation method devised by Neal [Stat. Comput. 11, 125 (2001)] to assign weights to configurations generated by simulated annealing trajectories.

Convective Replica-Exchange in Ergodic Regimes.

In a recent article (J. Comput. Chem.

Combining path-breaking with bidirectional nonequilibrium simulations to improve efficiency in free energy calculations.

An important limitation of unidirectional nonequilibrium simulations is the amount of realizations of the process necessary to reach suitable convergence of free energy estimates via Jarzynski's relationship [C. Jarzynski, Phys. Rev.

Path-breaking schemes for nonequilibrium free energy calculations.

We propose a path-breaking route to the enhancement of unidirectional nonequilibrium simulations for the calculation of free energy differences via Jarzynski's equality [C. Jarzynski, Phys. Rev.

Toward quantitative estimates of binding affinities for protein-ligand systems involving large inhibitor compounds: a steered molecular dynamics simulation route.

Understanding binding mechanisms between enzymes and potential inhibitors and quantifying protein-ligand affinities in terms of binding free energy is of primary importance in drug design studies. In this respect, several approaches based on molecular dynamics simulations, often combined with docking techniques, have been exploited to investigate the physicochemical properties of complexes of pharmaceutical interest. Even if the geometric properties of a modeled protein-ligand complex can be well predicted by computational methods, it is still challenging to rank with chemical accuracy a series of ligand analogues in a consistent way.

Tuning the emission properties of fluorescent ligands by changing pH: the unusual case of an acridine-containing polyamine macrocycle.

Synthesis and characterization of a new macrocyclic compound, composed by a triethylentetraamine chain linking the 4 and 5 positions of an acridine moiety, are reported. The molecule, devised as a fluorescent chemosensor for anions, has revealed an intriguing pH-dependent spectroscopic behavior, whose features are the specific object of this article. Ligand protonation in aqueous solution has been analyzed by means of potentiometric, (1)H NMR, UV-vis, and fluorescence emission measurements.