A theoretical investigation of ligand-stabilized MX diatomics (M = group 13, X = group 15 element) with N-heterocyclic carbene (NHC) ligands has been carried out to assess bonding and electronic structure. Binding of two ligands in the form L-MX-L is generally preferred over binding of a single ligand as L-MX or MX-L. Binding of carbene donor ligands is predicted to be thermodynamically favorable for all the systems, and is very favorable for the lighter group 15 systems (nitrogen and phosphorus). Detailed analysis of the bonding in these complexes has been carried out with energy decomposition analysis (EDA). In all cases, the carbene to boron and carbene to nitrogen bonding is described as an electron-sharing double bond with both σ and π bonding interactions. For the heavier elements, bonding to C (except for PC interactions) is best described as a donor-acceptor σ single bond.

As a complement to virtual screening, de novo design of small molecules is an alternative approach for identifying potential drug candidates. Here, we present a new 3D genetic algorithm to evolve molecules through breeding, mutation, fitness pressure, and selection. The method, termed DOCK_GA, builds upon and leverages powerful sampling, scoring, and searching routines previously implemented into DOCK6. Three primary experiments were used during development: Single-molecule evolution evaluated three selection methods (elitism, tournament, and roulette), in four clinically relevant systems, in terms of mutation type and crossover success, chemical properties, ensemble diversity, and fitness convergence, among others. Large scale benchmarking assessed performance across 651 different protein-ligand systems. Ensemble-based evolution demonstrated using multiple inhibitors simultaneously to seed growth in a SARS-CoV-2 target. Key takeaways include: (1) The algorithm is robust as demonstrated by the successful evolution of molecules across a large diverse dataset. (2) Users have flexibility with regards to parent input, selection method, fitness function, and molecular descriptors. (3) The program is straightforward to run and only requires a single executable and input file at run-time. (4) The elitism selection method yields more tightly clustered molecules in terms of 2D/3D similarity, with more favorable fitness, followed by tournament and roulette.

A series of di- and polymetal complexes involving closed-shell, heavy main-group atoms and ions shows a selection of special physical properties. These involve short metal-metal contacts, low entropies of formation and, most interestingly, strong Raman bands at low wavenumbers. These results together with the constitution of the coordination compounds, where the majority of electrons are assembled on the highly polarizable metal atoms and ions, experimental results have been interpreted in terms of direct, partial covalent metal-metal bonding. Previous theoretical studies have challenged this view and instead attributed the obvious attractive forces involved to secondary-type of interactions, such as dispersion. This study utilizes a multitude of theoretical tools, such as natural bond order (NBO) and natural energy decomposition analysis (NEDA), non-covalent interaction (NCI) analysis, electron localization functions (ELFs), and atoms-in-molecules (AIM) to characterize the interactions in models comprising closed-shell dimers, as well as experimentally studied ring and cage systems constituting the main reason for the hypotheses on metal-metal interactions. The results show that all experimental results can be attributed to the covalent interactions between the electron-rich, metal centers and the bridging anions in ring and cage coordination compounds of high symmetry, where the experimentally observed effects can be traced to the combination of covalent interactions between the metal centers and the anions along the edges of the ring and cage systems in combination with the cooperative effects generated by the high symmetry of these ring and cage systems.

The bonding and electronic properties of Inn - , Inn Si- , and Inn Ge- (n = 3-16) clusters have been computationally investigated. An intensive global search for the ground-state structures of these clusters were conducted using the genetic algorithm coupled with density functional theory (DFT). The ground-state structures of these clusters have been identified through the comparison between simulated photoelectron spectra (PES) of the found lowest-energy isomers and the experimentally measured ones. Doping semiconductor atom (Si or Ge) can significantly change the structures of the In clusters in most sizes, and the dopant prefers to be surrounded by In atoms. There are three structural motifs for Inn X- (X = Si, Ge, n = 3-16), and the transition occurs at sizes n = 5 and 13. All Inn Si- and Inn Ge- share the same configurations and similar electronic properties except for n = 8. Among all above studied clusters, In13 - stands out with the largest vertical detachment energy (VDE), HOMO-LUMO gap, (Eb ) and second order energy difference Δ2 E due to its closed electronic shell of (1S)2 (1P)6 (1D)10 (2S)2 (1F)14 (2P)6 . Similarly, the neutral In12 X (X = Si, Ge) clusters are also identified as superatoms but with electronic configuration of (1S)2 (1P)6 (2S)2 (1D)10 (1F)14 (2P)6 .

The main photophysical properties, useful for establishing whether hypericin in anionic form and some of its derivatives containing heavy atoms such as iodine, can be proposed for their use in photodynamic therapy, were determined using density functional based computations. The results showed that in the anionic form and in the iodinated derivatives, the absorption wavelength undergoes a bathochromic shift, the singlet-triplet energy gap assumes values ​that allow to excite the oxygen molecule from its ground to the excited singlet state, and that the spin-orbit couplings between singlet and triplet states significantly increase.

The present study consists in a novel computational protocol to model the UV-circular dichroism spectra of solvated species. It makes use of quantum-chemical calculations on a series of conformations of a flexible chromophore or on a series of chromophore/solvent clusters extracted from molecular dynamic simulations. The protocol is described and applied to the aqueous cationic tripeptide GAG+ and to the aqueous neutral decapeptide (GVGVP)2 . The protocol has proven able to: (i) properly consider the conformational motion of solute in the given environment; (ii) give the actual statistical weight of each conformational state; (iii) provide a reliable quantum mechanical method able to reproduce the spectral features. Temperature effects on conformations and spectral properties are properly taken into account. The role of explicit solvent on the conformational analysis and the spectra calculation is discussed. The comparison of the calculated circular dichroism spectra with experimental ones recorded at different temperatures represents a strict validation test of the method.

Pyranose ring pucker is a key coordinate governing the structure, interactions and reactivity of carbohydrates. We assess the ability of the machine learning potentials, ANI-1ccx and ANI-2x, and the GFN2-xTB semiempirical quantum chemical method, to model ring pucker conformers of five monosaccharides and oxane in the gas phase. Relative to coupled-cluster quantum mechanical calculations, we find that ANI-1ccx most accurately reproduces the ring pucker energy landscape for these molecules, with a correlation coefficient r2 of 0.83. This correlation in relative energies lowers to values of 0.70 for ANI-2x and 0.60 for GFN2-xTB. The ANI-1ccx also provides the most accurate estimate of the energetics of the 4 C1 -to-1 C4 minimum energy pathway for the six molecules. All three models reproduce chair more accurately than non-chair geometries. Analysis of small model molecules suggests that the ANI-1ccx model favors puckers with equatorial hydrogen bonding substituents; that ANI-2x and GFN2-xTB models overstabilize conformers with axially oriented groups; and that the endo-anomeric effect is overestimated by the machine learning models and underestimated via the GFN2-xTB method. While the pucker conformers considered in this study correspond to a gas phase environment, the accuracy and computational efficiency of the ANI-1ccx approach in modeling ring pucker in vacuo provides a promising basis for future evaluation and application to condensed phase environments.

The absorption spectra of polymers derived from ortho, meta and para phenylenediamines (o-PDA, m-PDA and p-PDA) have been simulated combining periodic density functional theory (DFT) calculations with time-dependent DFT simulations. These latter have been carried out on finite clusters embedded in a set of point charges devised to exactly reproduce the electrostatic potential of the periodic chains. The results are compared with those obtained for solvated o-PDA, m-PDA and p-PDA oligomers of increasing sizes extracted from the periodic structures. The electronic transitions involved have been investigated by a qualitative analysis based on isodensity maps completed by a quantitative analysis based on the density-based index (DCT ). For poly-(o)- and poly-(p)- phenylenediamines the agreement with the experimental data is achieved already by modeling solvated dimers whereas the inclusion of long-range electrostatic effects is mandatory for poly-(m)-phenylenediamine highlighting the importance of an accurate treatment of the electrostatic environment when a finite cluster approach is considered.