The noncovalent chalcogen interaction between SO2/SO3 and diazines was studied through a dispersion-corrected DFT Kohn-Sham molecular orbital together with quantitative energy decomposition analyses. For this, supramolecular circular chains of up to 12 molecules were built with the aim of checking the capability of diazine molecules to detect SO2/SO3 compounds within the atmosphere. Trends in the interaction energies with the increasing number of molecules are mainly determined by the Pauli steric repulsion involved in these σ-hole/π-hole interactions. But more importantly, despite the assumed electrostatic nature of the involved interactions, the covalent component also plays a determinant role in its strength in the involved chalcogen bonds. Noticeably, π-hole interactions are supported by the charge transfer from diazines to SO2/SO3 molecules. Interaction energies in these supramolecular complexes are not only determined by the S···N bond lengths but attractive electrostatic and orbital interactions also determine the trends. These results should allow us to establish the fundamental characteristics of chalcogen bonding based on its strength and nature, which is of relevance for the capture of sulfur oxides.

BACKGROUND: Organic halides stand as invaluable reagents with diverse applications in synthetic chemistry and various industrial processes. Despite their utility, concerns arise due to their inherent toxicity. Addressing these apprehensions, hydro-dehalogenation has emerged as a promising strategy involving the replacement of halogen atoms with hydrogen atoms to transform toxic organic halides into hydrocarbons. This study delves into the computational exploration of hydro-dehalogenation reactions of benzyl halide, mediated by frustrated Lewis pairs (FLPs), using density functional theory (DFT). The reactions entail the formation of FLP1 or FLP2 in the presence of TMP or lutidine with B(C6F5)3, respectively. This is followed by heterolytic cleavage of dihydrogen and subsequent reaction with benzyl halides. Non-covalent interaction analysis underscores the significance of π-π stacking and CH-π interactions in stabilizing transition states. Additionally, the activation strain model (ASM) dissects activation energies, revealing the substantial impact of strain energy on reaction barriers. Energy decomposition analysis (EDA) offers insights into the contributions of electrostatic, orbital, and dispersion energies to the overall attractive interaction energy. The investigation extends to hydro-dehalogenation reactions of ethyl halides, uncovering distinct mechanisms and activation barriers. This comprehensive analysis illuminates the intricacies of hydro-dehalogenation reactions, providing valuable insights into their mechanisms and paving the way for future studies in this field.
METHODS: Geometry optimizations were carried out at the M06-2X/def2-SVP level of theory, which was performed using the Gaussian 16 program. Solvent-corrected single-point energies were also calculated using the polarizable continuum model (PCM) at the PCM(chloroform)-M06-2X/def2-TZVP//M06-2X/def2-SVP level of theory. The Gibbs free energy correction was determined from computations performed at the M06-2X/def2-SVP level of theory. Principal interacting orbital (PIO) analysis was conducted using the NBO 6.0 software. The nature of bonding in the respective transition state (TS) structures was analyzed using atoms-in-molecules (AIM) analyses. Additionally, the presence of non-covalent interactions (NCI) was exemplified using Multiwfn software.

The cooperative mechanism is of paramount importance in the synthesis of supramolecular polymers with desired characteristics, including molecular mass, polydispersity, and morphology. It is primarily driven by the presence of intermolecular interactions, which encompass strong hydrogen bonding, metal-ligand interactions, and dipole-dipole interactions. In this study, we utilize density functional theory and energy decomposition analysis to investigate the cooperative behavior of perylene diimide (PDI) oligomers with alkyl chains at their imide positions, which lack the previously mentioned interactions. Our systematic examination reveals that dispersion interactions originating from the alkyl side-chain substituents play an important role in promoting cooperativity within these PDIs. This influence becomes even more pronounced for alkyl chain lengths beyond hexyl groups. The energy decomposition analysis reveals that the delicate balance between dispersion energy and Pauli repulsion energy is the key driver of cooperative behavior in PDIs. Additionally, we have developed a mathematical model capable of predicting the saturated binding energies for PDI oligomers of varying sizes and alkyl chain lengths. Overall, our findings emphasize the previously undervalued significance of dispersion forces in cooperative supramolecular polymerization, enhancing our overall understanding of the cooperative mechanism.

Cyclodextrins (CDs) were used as green char promoters in the formulation of organophosphorus flame retardants (OPFRs) for polymeric materials, and they could reduce the amount of usage of OPFRs and their release into the environment by forming [host:guest] inclusion complexes with them. Here, we report a systematic study on the inclusion complexes of natural CDs (α-, β-, and γ-CD) with a representative OPFR of DOPO using computational methods of molecular docking, molecular dynamics (MD) simulations, and quantum mechanical (QM) calculations. The binding modes and energetics of [host:guest] inclusion complexes were analyzed in details. α-CD was not able to form a complete inclusion complex with DOPO, and the center of mass distance [host:guest] distance amounted to 4-5 Å. β-CD and γ-CD allowed for a deep insertion of DOPO into their hydrophobic cavities, and DOPO was able to frequently change its orientation within the γ-CD cavity. The energy decomposition analysis based on the dispersion-corrected density functional theory (sobEDAw) indicated that electrostatic, orbital, and dispersion contributions favored [host:guest] complexation, while the exchange-repulsion term showed the opposite. This work provides an in-depth understanding of using CD inclusion complexes in OPFRs formulations.

The clinical success of [223Ra]RaCl2 (Xofigo®) for the palliative treatment of bone metastases in patients with prostate cancer has highlighted the therapeutic potential of α-particle emission. Expanding the applicability of radium-223 in Targeted Alpha Therapy of non-osseous tumors is followed up with significant interest, as it holds the potential to unveil novel treatment options in the comprehensive management of cancer. Moreover, the use of barium radionuclides, like barium-131 and -135m, is still unfamiliar in nuclear medicine applications, although they can be considered as radium-223 surrogates for imaging purposes. Enabling these applications requires the establishment of chelators able to form stable complexes with radium and barium radionuclides. Until now, only a limited number of ligands have been suggested and these molecules have been primarily inspired by existing structures known for their ability to complex large metal cations. However, a systematic inspection of chelators specifically tailored to Ra2+ and Ba2+ has yet to be conducted. This work delves into a comprehensive investigation of a series of small organic ligands, aiming to unveil the coordination preferences of both radium-223 and barium-131/135m. Electronic binding energies of both metal cations to each ligand were theoretically computed via Density Functional Theory calculations (COSMO-ZORA-PBE-D3/TZ2P), while thermodynamic stability constants were experimentally determined for Ba2+-ligand complexes by potentiometry, NMR and UV-Vis spectroscopies. The outcomes revealed malonate, 2-hydroxypyridine 1-oxide and picolinate as the most favorable building blocks to design multidentate chelators. These findings serve as foundation guidelines, propelling the development of cutting-edge radium-223- and barium-131/135m-based radiopharmaceuticals for Targeted Alpha Therapy and theranostics of cancer.

Halogen bonds are typically observed to have a linear arrangement with a 180° angle between the nucleophile and the halogen bond acceptor X-R. This linearity is commonly explained using the σ-hole model, although there have been alternative explanations involving exchange repulsion forces. We employ two-dimensional Distortion/Interaction and Energy Decomposition Analysis to examine the archetypal H3 N⋯X2 halogen bond systems. Our results indicate that although halogen bonds are predominantly electrostatic, their directionality is largely due to decreased Pauli repulsion in linear configurations as opposed to angled ones in the I2 and Br2 systems. As we move to the smaller halogens, Cl2 and F2 , the influence of Pauli repulsion diminishes, and the energy surface is shaped by orbital interactions and electrostatic forces. These results support the role of exchange repulsion forces in influencing the directionality of strong halogen bonds. Additionally, we demonstrate that the 2D Energy Decomposition Analysis is a useful tool for enhancing our understanding of the nature of potential energy surfaces in noncovalent interactions.

This study presents a comprehensive analysis of nickel-phosphine complexes, specifically Ni(PH3)2(OCCH2), Ni(PH3)2(H2CCO), Ni(PH3)2(H2CCCH2), Ni(PH3)2(NNCH2), and Ni(PH3)2(η1-H2CNN). Utilizing ETS-NOCV analysis, we explored orbital energy decomposition and the Hirshfeld charges of the ligands, providing insights into the electronic structures and donor-acceptor interactions within these complexes. The interactions in the ketene and allene complexes exhibit similar deformation densities and NOCV orbital shapes to those calculated for Ni(PH3)2(NNCH2), indicating consistent interaction characteristics across these complexes. The total interaction energy for all η2 complexes is observed to be over 60 kcal/mol, slightly exceeding that of the analogous carbon dioxide complex reported earlier. Furthermore, the study highlights the stronger back-donation as compared to donor interactions across all η2 complexes. This is further corroborated by Hirshfeld analysis, revealing the charge distribution dynamics within the ligand fragments. The research offers new perspectives on the electron distribution and interaction energies in nickel-phosphine complexes, contributing to a deeper understanding of their catalytic and reactive behaviors.

Energy decomposition analysis is one of the most attractive features of fragment molecular orbital (FMO) calculations from the point of view of practical applications. Here we report some enhancements for PIEDA in the ABINIT-MP program. One is a separation of the dispersion-type stabilization from the electron correlation energy, traditionally referred to as the \"dispersion interaction\" (DI). Another is an alternative evaluation of the electrostatic (ES) interaction using the restrained electrostatic potential (RESP) charges. The GA:CT stacked base pair and the Trp-Cage miniprotein were used as illustrative examples.

The activation of H2 by pyramidalized boron-based frustrated Lewis Pairs (FLPs) (B/E-FLP systems where \"E\" refers to N, P, As, Sb, and Bi) have been explored using density functional theory (DFT) based computational study. The activation pathway for the entire process is accurately characterized through the utilization of the activation strain model (ASM) of reactivity, shedding light on the underlying physical factors governing the process. The study also explores the hydrogenation process of multiple bonds with the help of B/N-FLP. The research findings demonstrate that the liberation of activated dihydrogen occurs in a synchronized, albeit noticeably asynchronous, fashion. The transformation is extensively elucidated using the activation strain model and the energy decomposition analysis. This approach suggests a co-operative double hydrogen-transfer mechanism, where the B-H hydride triggers a nucleophilic attack on the carbon atom of the multiple bonds, succeeded by the migration of the protic N-H.

Benzofuran, 1,3,4-oxadiazole, and 1,2,4-triazole are privileged heterocyclic moieties that display the most promising and wide spectrum of biological activities against a wide variety of diseases. In the current study, benzofuran-1,3,4-oxadiazole BF1-BF7 and benzofuran-1,2,4-triazole compounds BF8-BF15 were tested against HCV NS5B RNA-dependent RNA polymerase (RdRp) utilizing structure-based screening via a computer-aided drug design (CADD) approach. A molecular docking approach was applied to evaluate the binding potential of benzofuran-appended 1,3,4-oxadiazole and 1,2,4-triazole BF1-BF15 molecules. Benzofuran-1,3,4-oxadiazole scaffolds BF1-BF7 showed lesser binding affinities (-12.63 to -14.04 Kcal/mol) than benzofuran-1,2,4-triazole scaffolds BF8-BF15 (-14.11 to -16.09 Kcal/mol) against the HCV NS5B enzyme. Molecular docking studies revealed the excellent binding affinity scores exhibited by benzofuran-1,2,4-triazole structural motifs BF-9 (-16.09 Kcal/mol), BF-12 (-15.75 Kcal/mol), and BF-13 (-15.82 Kcal/mol), respectively, which were comparatively better than benzofuran-based HCV NS5B inhibitors\' standard reference drug Nesbuvir (-15.42 Kcal/mol). A molecular dynamics simulation assay was also conducted to obtain valuable insights about the enzyme-compounds interaction profile and structural stability, which indicated the strong intermolecular energies of the BF-9+NS5B complex and the BF-12+NS5B complex as per the MM-PBSA method, while the BF-12+NS5B complex was the most stable system as per the MM-GBSA calculation. The drug-likeness and ADMET studies of all the benzofuran-1,2,4-triazole derivatives BF8-BF15 revealed that these compounds possessed good medicinal chemistry profiles in agreement with all the evaluated parameters for being drugs. The molecular docking affinity scores, MM-PBSA/MM-GBSA and MD-simulation stability analysis, drug-likeness profiling, and ADMET study assessment indicated that N-4-fluorophenyl-S-linked benzofuran-1,2,4-triazole BF-12 could be a future promising anti-HCV NS5B RdRp inhibitor therapeutic drug candidate that has a structural agreement with the Nesbuvir standard reference drug.