Implementation of machine learning protocols to predict the hydrolysis reaction properties of organophosphorus substrates using descriptors of electron density topology.

Prediction of catalytic reaction efficiency is one of the most intriguing and challenging applications of machine learning (ML) algorithms in chemistry. In this study, we demonstrated a strategy for utilizing ML protocols applied to Quantum Theory of Atoms In Molecules (QTAIM) parameters to predict the ability of the A17 L47K catalytic antibody to covalently capture organophosphate pesticides. We found that the novel "composite" DFT functional B97-3c could be effectively employed for fast and accurate initial geometry optimization, aligning well with the input dataset creation. QTAIM descriptors proved to be well-established in describing the examined dataset using density-based and hierarchical clustering algorithms. The obtained clusters exhibited correlations with the chemical classes of the input compounds. The precise physical interpretation of the QTAIM properties simplifies the explanation of feature impact for both supervised and unsupervised ML protocols. It also enables acceleration in the search for entries with desired properties within large databases. Furthermore, our findings indicated that Ridge Regression with Laplacian kernel and CatBoost Regressor algorithms demonstrated suitable performance in handling small datasets with non-trivial dependencies. They were able to predict the actual reaction barrier values with a high level of accuracy. Additionally, the CatBoost Classifier proved reliable in discriminating between "active" and "inactive" compounds.

Response of the mechanical and chiral character of ethane to ultra-fast laser pulses.

A pair of simulated left and right circularly polarized ultra-fast laser pulses of duration 20 femtoseconds that induce a mixture of excited states are applied to ethane. The response of the electron dynamics is investigated within the next generation quantum theory of atoms in molecules (NG-QTAIM) using third-generation eigenvector-trajectories which are introduced in this work. This enables an analysis of the mechanical and chiral properties of the electron dynamics of ethane without needing to subject the C-C bond to external torsions as was the case for second-generation eigenvector-trajectories. The mechanical properties, in particular, the bond-flexing and bond-torsion were found to increase depending on the plane of the applied laser pulses. The bond-flexing and bond-torsion, depending on the plane of polarization, increases or decreases after the laser pulses are switched off. This is explainable in terms of directionally-dependent effects of the long-lasting superpositions of excited states. The chiral properties correspond to the ethane molecule being classified as formally achiral consistent with previous NG-QTAIM investigations. Future planned investigations using ultra-fast circularly polarized lasers are briefly discussed.

Exchange-correlation effects in interatomic energies for pure density functionals and their application to the molecular energy prediction.

In this proof-of-concept paper, we show how exchange-correlation effects can be simply recovered for interatomic energies within the interacting quantum atoms decomposition when local, gradient generalized, or meta-gradient generalized approximations are used in density functional theory (DFT) calculations. We also demonstrate how inhomogeneity and non-local effects can be introduced even from a pure local scheme, without resorting to any orbital information. Finally, we provide numerical evidence on a database of selected energetic molecules that this decomposition scheme can be efficiently used to build accurate models for the prediction of molecular energies from an initial "cheap" DFT calculation.

Determining the Factors Accounting for Reaction Selectivity: A Relative Energy Gradient - Interacting Quantum Atoms and Natural Bonding Orbitals Study.

Identifying the main physicochemical properties accounting for the course of a reaction is of utmost importance to rationalize chemical syntheses. To this aim, the relative energy gradient (REG) method is an appealing approach because it is an unbiased and automatic process to extract the most relevant pieces of energy information. Initially formulated within the interacting quantum atoms (IQA) framework for a single reaction, here we extend the REG method to natural bond orbitals (NBO) analysis and to the case of two competitive processes. This development enables the determination of the driving forces of any chemical selectivity. We illustrate the extended REG method on the case study of ring opening in cyclobutenes, which is an important instance of the so-called torquoselectivity.

Does Aromaticity Play a Role in Electronic and Structural Properties of YBn (n=2-14) Clusters?

Nanoclusters exhibit electronic, optical, and magnetic properties that differ significantly from those of extended and molecular systems with comparable stoichiometries. In this work, we examined the structural, energetic, and electronic characteristics of yttrium-doped boron clusters (YBn,  n =2-14) with robust wavefunction analysis tools. Special emphasis is placed on the elucidation of the potential aromatic character exhibited by the resultant molecules and how it can affect their chemical bonding and stability. Our results revealed that the YBn stability is governed by the maximization of the ionic Y-B interactions. This is evidenced from the lowest-energy conformations, which manifest as half-sandwich structures wherein the majority of boron atoms are bonded to yttrium. The stabilization of such chemical contacts comes at the expense of a notorious depletion of the Y local electron density, crystallizing in a considerable ionic character, close to Y2+ + Bn2-. Such a  charge transfer is coupled to the enhancement of the electron delocalization within the YBn lattice, resulting in quite remarkable local and global aromatic characters. Altogether, this study shows how the toolkit of real space chemical bonding descriptors can offer valuable insights into the structural and electronic properties,  of YBn clusters, contributing to a better understanding of their behavior.

Theoretical Insights into Bifurcated Intramolecular Dihydrogen Bonds.

Two-ring intramolecular π-electron delocalization assisted dihydrogen bonds existing in (1Z,4Z)-1,4-dipentene-3-bora-1,5-diol and its symmetrically substituted derivatives have been analysed here since the MP2/6-311++G(d,p) calculations on these systems were performed. The influence of the coexistence of two intramolecular dihydrogen bonded rings in these molecular structures on properties of intramolecular dihydrogen bonds as well as on the π-electron delocalization within these rings was investigated. The comparison with corresponding structures of typical two-ring, so-called resonance-assisted, RAHB, systems was performed. The results of calculations show that such rings' coexistence leads to the weakening of dihydrogen bonds, similarly as for the typical two-ring RAHB systems. The Quantum Theory of ''Atoms in Molecules'' (QTAIM) was also applied here to get more details about the nature of dihydrogen bonds. Correlations between dihydrogen bond strength measures and other energetic, geometrical and topological parameters were also analysed. It was found that characteristics of bond critical points as well as of ring critical points are useful to estimate the strength of intramolecular dihydrogen bonds in two-ring dihydrogen bonded systems discussed here. The Natural Bond Orbital, NBO, approach parameters are also discussed as useful ones to describe properties of dihydrogen bonded systems.

Exploring the Efficiency of Algerian Kaolinite Clay in the Adsorption of Cr(III) from Aqueous Solutions: Experimental and Computational Insights.

The current study comprehensively investigates the adsorption behavior of chromium (Cr(III)) in wastewater using Algerian kaolinite clay. The structural and textural properties of the kaolinite clay are extensively characterized through a range of analytical methods, including XRD, FTIR, SEM-EDS, XPS, laser granulometry, N2 adsorption isotherm, and TGA-DTA. The point of zero charge and zeta potential are also assessed. Chromium adsorption reached equilibrium within five minutes, achieving a maximum removal rate of 99% at pH 5. Adsorption equilibrium is modeled using the Langmuir, Freundlich, Temkin, Elovich, and Dubinin-Radushkevitch equations, with the Langmuir isotherm accurately describing the adsorption process and yielding a maximum adsorption capacity of 8.422 mg/g for Cr(III). Thermodynamic parameters suggest the spontaneous and endothermic nature of Cr(III) sorption, with an activation energy of 26.665 kJ/mol, indicating the importance of diffusion in the sorption process. Furthermore, advanced DFT computations, including COSMO-RS, molecular orbitals, IGM, RDG, and QTAIM analyses, are conducted to elucidate the nature of adsorption, revealing strong binding interactions between Cr(III) ions and the kaolinite surface. The integration of theoretical and experimental data not only enhances the understanding of Cr(III) removal using kaolinite but also demonstrates the effectiveness of this clay adsorbent for wastewater treatment. Furthermore, this study highlights the synergistic application of empirical research and computational modeling in elucidating complex adsorption processes.

An atoms-in-molecules characterization of the nature of the OO bond in peroxides and nitroxide dimers.

The quantum theory of atoms-in-molecules (QTAIM) method is used to examine the OO bond in peroxides (RO-OR) and nitroxide dimers (R2 NO-ONR2 ), including Fremy's salt. The electron density (ρ), electron kinetic energy density [K(ρ)], and Laplacian of the electron density (∇2 ρ) at bond critical points characterize the nature of the OO bond. The data distinguish OO bonding of two kinds. Large values of ρ and positive ∇2 ρ and K(ρ) suggest that simple peroxides have charge-shift bonds. Nitroxide dimers, with smaller ρ, positive ∇2 ρ, and near-zero K(ρ), show a lack of shared electron density, suggesting there is no conventional OO bonding in these molecules. QTAIM analysis at the B3LYP/6-311+G(d,p) level of theory gives results in agreement with valence-bond theory and X-ray diffraction characterizations of peroxide OO bonds as charge-shift bonds. In contrast, CCSD/cc-pVDZ calculations fail to agree with previous results because of an insufficient, single-determinant treatment of the charge-shift bond.

A building-block database of distributed polarizabilities and dipole moments to estimate optical properties of biomacromolecules in isolation or in an explicitly solvated medium.

Since atomic or functional-group properties in the bulk are generally not available from experimental methods, computational approaches based on partitioning schemes have emerged as a rapid yet accurate pathway to estimate the materials behavior from chemically meaningful building blocks. Among several applications, a comprehensive and systematically built database of atomic or group polarizabilities and related opto-electronic quantities would be very useful not only to envisage linear or non-linear optical properties of biomacromolecules but also to improve the accuracy of classical force fields devoted to simulate biochemical processes. In this work, we propose the first entries of such database that contains distributed polarizabilities and dipole moments extracted from fragments of peptides. Twenty three prototypical conformers of the dipeptides alanine-alanine and glycine-glycine were used to extract functional groups such as CH2 , CHCH3 , NH2 , COOH, CONH, thus allowing construction of a diversity of chemically relevant environments. To evaluate the accuracy of our database, reconstructed properties of larger peptides containing up to six residues of alanine and glycine were tested against density functional theory calculations at the M06-HF/aug-cc-pVDZ level of theory. The procedure is particularly accurate for the diagonal components of the polarizability tensor with errors up to 15%. In order to include solvent effects explicitly, the peptides were also surrounded by a box of water molecules whose distribution was optimized using the CHARMM force field. Solvent effects introduced by a classical dipole-dipole interaction model were compared to those obtained from polarizable-continuum model calculations.

Origin of structure and stability of M@C18 (M = Cu, Ag, and Au) complexes with D9h point group.

Theoretical predictions and recent experimental studies lead to the discovery of an exciting new member of the carbon allotrope family polyynic cyclo[18]carbon (C18 ). Present investigation aims to probe the structure, stability, and properties of coinage metal (M)@C18 complexes using density functional theory (DFT) calculations. The DFT results unequivocally show that even Cu@C18 , Ag@C18 , and Au@C18 complexes substantially preserve the ground state polyynic structure of C18 . It is also worth to mention that only Au@C18 is a stable D9h structure, however the symmetry is distorted in the case of Cu@C18 and Ag@C18 . Due to computational limitations, in this investigation the M@C18 complexes were scrutinized using the C2v sub abelian group of D9h . The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of D9h conformers are a singlet a1 and two same value singlets a1 ⊕ b1 generated from doublet e, respectively. The non-covalent interaction index (NCI), quantum theory of atoms in molecule (QTAIM), and energy decomposition analysis (EDA) vividly explains the interaction between a coinage metal atom and C18 ring. It is found from the results that the stability of Cu@C18 Ag@C18 , and Au@C18 is governed by the attractive electrostatic, orbital and dispersion interaction.

Aza-Michael Addition in Explicit Solvent: A Relative Energy Gradient-Interacting Quantum Atoms Study.

Aza-Michael additions are key reactions in organic synthesis. We investigate, from a theoretical and computational point of view, several examples ranging from weak to strong electrophiles in dimethylsulfoxide treated as explicit solvent. We use the REG-IQA method, which is a quantum topological energy decomposition (Interacting Quantum Atoms, IQA) coupled to a chemical-interpretation calculator (Relative Energy Gradient, REG). We focus on the rate-limiting addition step in order to unravel the different events taking place in this step, and understand the influence of solvent on the reaction, with an eye on predicting the Mayr electrophilicity. For the first time, a link is established between an REG-IQA analysis and experimental values.

Ga···C Triel Bonds-Why They Are Not Strong Enough to Change Trigonal Configuration into Tetrahedral One: DFT Calculations on Dimers That Occur in Crystal Structures.

Structures characterized by the trigonal coordination of the gallium center that interacts with electron rich carbon sites are described. These interactions may be classified as Ga···C triel bonds. Their properties are analyzed in this study since these interactions may be important in numerous chemical processes including catalytical activities; additionally, geometrical parameters of corresponding species are described. The Ga···C triel bonds discussed here, categorized also as the π-hole bonds, do not change the trigonal configuration of the gallium center into the tetrahedral one despite total interactions in dimers being strong; however, the main contribution to the stabilization of corresponding structures comes from the electrostatic forces. The systems analyzed theoretically here come from crystal structures since the Cambridge Structural Database, CSD, search was performed to find structures where the gallium center linked to CC bonds of Lewis base units occurs. The majority structures found in CSD are characterized by parallel, stacking-like arrangements of species containing the Ga-centers. The theoretical results show that interactions within dimers are not classified as the three-centers links as in a case of typical hydrogen bonds and numerous other interactions. The total interactions in dimers analyzed here consist of several local intermolecular atom-atom interactions; these are mainly the Ga···C links. The DFT results are supported in this study by calculations with the use of the quantum theory of atoms in molecules, QTAIM, the natural bond orbital, NBO, and the energy decomposition analysis, EDA, approaches.

Inverse Versus Normal Behavior of Interactions, Elucidated Based on the Dynamic Nature with QTAIM Dual-Functional Analysis.

In QTAIM dual-functional analysis, Hb(rc) is plotted versus Hb(rc) - Vb(rc)/2 for the interactions, where Hb(rc) and Vb(rc) are the total electron energy densities and potential energy densities, respectively, at the bond critical points (BCPs) on the interactions in question. The plots are analyzed by the polar (R, θ) coordinate representation for the data from the fully optimized structures, while those from the perturbed structures around the fully optimized structures are analyzed by (θp, κp). θp corresponds to the tangent line of the plot, and κp is the curvature; θ and θp are measured from the y-axis and y-direction, respectively. The normal and inverse behavior of interactions is proposed for the cases of θp > θ and θp < θ, respectively. The origin and the mechanism for the behavior are elucidated. Interactions with θp < θ are typically found, although seldom for [F-I-∗-F]-, [MeS-∗-TeMe]2+, [HS-∗-TeH]2+ and CF3SO2N-∗-IMe, where the asterisks emphasize the existence of BCPs in the interactions and where [Cl-Cl-∗-Cl]- and CF3SO2N-∗-BrMe were employed as the reference of θp > θ. The inverse behavior of the interactions is demonstrated to arise when Hb(rc) - Vb(rc)/2 and when the corresponding Gb(rc), the kinetic energy densities at BCPs, does not show normal behavior.

Comprehensive Study of the Ammonium Sulfamate-Urea Binary System.

The physicochemical properties of binary systems are of great importance for the application of the latter. We report on the investigation of an ammonium sulfamate-urea binary system with different component ratios using a combination of experimental (FTIR, XRD, TGA/DSC, and melting point) and theoretical (DFT, QTAIM, ELF, RDG, ADMP, etc.) techniques. It is shown that, at a temperature of 100 °C, the system under study remains thermally and chemically stable for up to 30 min. It was established using X-ray diffraction analysis that the heating time barely affects the X-ray characteristics of the system. Data on the aggregate states in specified temperature ranges were obtained with thermal analysis and determination of the melting point. The structures of the ammonium sulfamate-urea system with different component ratios were optimized within the density functional theory. The atom-centered density matrix propagation calculation of the ammonium sulfamate-urea system with different component ratios was performed at temperatures of 100, 300, and 500 K. Regardless of the component ratio, a regular increase in the potential energy variation (curve amplitude) with an increase in temperature from 100 to 500 K was found.

Dynamic and Static Nature of XH-∗-π and YX-∗-π (X = F, Cl, Br, and I; Y = X and F) in the Distorted π-System of Corannulene Elucidated with QTAIM Dual Functional Analysis.

The dynamic and static nature of the XH-∗-π and YX-∗-π (X = F, Cl, Br, and I; Y = X and F) interactions in the distorted π-system of corannulene (π(C20H10)) is elucidated with a QTAIM dual functional analysis (QTAIM-DFA), where asterisks emphasize the presence of bond critical points (BCPs) on the interactions. The static and dynamic nature originates from the data of the fully optimized and perturbed structures, respectively, in QTAIM-DFA. On the convex side, H in F-H-∗-π(C20H10) and each X in Y-X-∗-π(C20H10) join to C of the central five-membered ring in π(C20H10) through a bond path (BP), while each H in X-H-∗-π(C20H10) does so to the midpoint of C=C in the central five-membered ring for X = Cl, Br, or I. On the concave side, each X in F-X-∗-π(C20H10) also joins to C of the central five-membered ring with a BP for X = H, Cl, Br, and I; however, the interactions in other adducts are more complex than those on the convex side. Both H and X in X-H-∗-π(C20H10) (X = Cl and Br) and both Fs in F-F-∗-π(C20H10) connect to the three C atoms in each central five-membered ring (with three BPs). Two, three, and five BPs were detected for the Cl-Cl, I-H, Br-Br, and I-I adducts, where some BPs do not stay on the central five-membered ring in π(C20H10). The interactions are predicted to have a vdW to CT-MC nature. The interactions on the concave side seem weaker than those on the convex side for X-H-∗-π(C20H10), whereas the inverse trend is observed for Y-X-∗-π(C20H10) as a whole. The nature of the interactions in the π(C20H10) adducts of the convex and concave sides is examined in more detail, employing the adducts with X-H and F-X placed on their molecular axis together with the π(C24H12) and π(C6H6) adducts.

A real space picture of the role of steric effects in SN 2 reactions.

Within substitution reactions, the Bimolecular Nucleophilic Substitution (SN 2) reaction mechanism is one of the most frequently found and studied ones. Among other factors, the easiness of the SN 2 pathway is classically considered to be determined by steric hindrance. However, the diffuse nature of the latter inevitably darkens these and other arguments holding the pillars of chemical intuition. In this work, we employ the steric energy (EST ) descriptor, formulated within the Interacting Quantum Atoms approach, to offer insights regarding this problem. The steric demands of the substrate, nucleophile and leaving group were studied using the gas-phase SN 2 reaction with different organic skeletons (CH3 , CH3 CH2 , (CH3 )2 CH, (CH3 )3 C, (CH3 )3 CCH2 ) and halogens (F, Cl, and Br) as test-bed systems. Our results show that, according to EST , the SH experienced along these simple reactions fits, in the general case, the trends predicted by a meticulous and rigorous application of chemical intuition. However, steric clash alone should not be considered as the only argument used to explain the easiness of the SN 2 reaction over different electrophiles.

A fast approximate extension of the interacting quantum atoms energy decomposition to excited states.

An approach is developed for the fast calculation of the interacting quantum atoms energy decomposition (IQA) from the information contained in the first order reduced density matrix only. The proposed methodology utilizes an approximate exchange-correlation density from Density Matrix Functional Theory without the need to evaluate the correlation-exchange contribution directly. Instead, weight factors are estimated to decompose the exact Vxc into atomic and pairwise contributions. In this way, the sum of the IQA contributions recovers the energy obtained from the electronic structure calculation. This method can, hence, be applied to obtain atomic contributions in excited states on the same footing as in their ground states using any method that delivers the reduced first-order density matrix. In this way, one can locate chromophores from first principles quantum chemical calculations. Test calculations on the ground and excited states of a set of small molecules indicate that the scaled atomic contributions reproduce vertical electronic transition energies calculated exactly. This approach may be useful to extend the applicability of the IQA approach in the study of large photochemical systems especially when the calculations of the second order reduced density matrices is prohibitive or not possible.

The performance of exchange-correlation functionals in describing electron density parameters of saddle point structures along chemical reactions.

This work is focused on evaluating the performance of exchange-correlation functionals from density functional theory in providing descriptor values derived from the electron density of saddle point structures (transition states) in chemical reactions. The properties investigated were obtained from the quantum theory of atoms in molecules, including atomic charges and electron density topological data at the bond critical points. In addition, parameters from the Interacting quantum atom energy partition were used as well in this comparative study. The reference values are attained in coupled cluster calculations with iterative single and double excitations (CCSD). Six elementary reactions are considered here: CO + H2  â†” H2 CO, CO + H2 O â†” HCOOH, HCN â†” HNC, H + F2  â†” HF + F, H + N2  â†” HN2 , and H + CO â†” HCO. In general, the BB1K functional (hybrid-meta-generalized gradient approximation) provides the best description of these properties. Our study indicates that an intermediate percentage of nonlocal exact exchange, around 40%-55% (perhaps even larger), is probably required for attaining more accurate values with actual functionals, although this condition is not able of explaining all the trends observed.

Comprehensive Empirical Model of Substitution-Influence on Hydrogen Bonding in Aromatic Schiff Bases.

In this work, over 500 structures of tri-ring aromatic Schiff bases with different substitution patterns were investigated to develop a unified description of the substituent effect on the intramolecular hydrogen bridge. Both proximal and distal effects were examined using Density Functional Theory (DFT) in the gas phase and with solvent reaction field (Polarizable Continuum Model (PCM) and water as the solvent). In order to investigate and characterize the non-covalent interactions, a topological analysis was performed using the Quantum Theory of Atoms In Molecules (QTAIM) theory and Non-Covalent Interactions (NCI) index. The obtained results were summarized as the generalized, empirical model of the composite substituent effect, assessed using an additional group of simple ring-based Schiff bases. The composite substituent effect has been divided into separate increments describing the different interactions of the hydrogen bridge and the substituent: the classical substituent effect, involving resonance and induction mediated through the ring, steric increment based on substituent proximity to the bridge elements, and distal increment, derived from substitution on the distal ring.

Redox-Triggered Switching of Conformational State in Triple-Decker Lanthanide Phthalocyaninates.

Double- and triple-decker lanthanide phthalocyaninates exhibit unique physical-chemical properties, particularly single-molecule magnetism. Among other factors, the magnetic properties of these sandwiches depend on their conformational state, which is determined via the skew angle of the phthalocyanine ligands. Thus, in the present work we report the comprehensive conformational study of substituted terbium(III) and yttrium(III) trisphthalocyaninates in solution depending on the substituents at the periphery of molecules, redox-states and nature of solvents. Conjunction of UV-vis-NIR spectroscopy and quantum-chemical calculations within simplified time-dependent DFT in Tamm-Dancoff approximation provided the spectroscopic signatures of staggered and gauche conformations of trisphthalocyaninates. Altogether, it allowed us to demonstrate that the butoxy-substituted complex behaves as a molecular switcher with controllable conformational state, while the crown-substituted triple-decker complex maintains a staggered conformation regardless of external factors. The analysis of noncovalent interactions within the reduced density gradient approach allowed to shed light on the nature of factors stabilizing certain conformers.