Chemistry and Materials Science

Abstract: Marine cyclic peptides and depsipeptides constitute structurally complex natural products of considerable interest for drug discovery, but the relationship between their electronic reactivity and predicted pharmacokinetic behavior remains insufficiently characterized. In this work, five pairs of bioactive marine congeners, Callipeltins, Calyxamides, Rolloamides, Tamandarins, and Pipecolidepsins, were investigated using Conceptual Density Functional Theory within the Generalized Quadratic Model (GQM), complemented by KID consistency criteria, atom-resolved Fukui functions, frontier-orbital and electrostatic-potential analyses, and in silico ADMET predictions. The GQM/KID analysis revealed branch- and family-dependent electronic responses, including an exceptionally small electron-addition deviation for Tamandarin A, a larger corresponding deviation for Calyxamide A, pronounced A-to-B electronic reorganization for the Rolloamides, and comparatively larger electron-removal deviations for the Pipecolidepsins. Local reactivity patterns further differentiated the congeners, with approximately 98% of the Pipecolidepsin electron-removal response concentrated on the same N68–C67–C66–C65 region. Rolloamides showed the highest predicted intestinal absorption, followed by Tamandarins, whereas negligible absorption was predicted for the other families. Overall, electronic differentiation was not necessarily mirrored by predicted ADMET behavior, demonstrating that GQM/CDFT and pharmacokinetic profiling provide complementary dimensions for the computational characterization of complex marine natural products.

Abstract: Bovine chymosin (Chn) selectively cleaves the Phe105–Met106 bond of κ-casein (κ-CN), initiating milk coagulation. The molecular organization of the enzyme–substrate complex immediately preceding cleavage remains incompletely characterized. Here, AlphaFold3-based structural modeling, molecular docking, replicated molecular dynamics (MD), and quantum mechanics/molecular mechanics (QM/MM) calculations were combined to characterize the pre-reactive Chn/κ-CN complex. Ten independent 300-ns MD trajectories were generated for each modeled system. Chymosin predominantly sampled an open Tyr77 conformation near 300°, while substrate binding was stabilized by a network of contacts involving the His-Pro region of κ-CN. The Phe105–Met106 scissile region remained locally mobile relative to the Asp34/Asp216 catalytic dyad, indicating a dynamically organized rather than rigid pre-reactive geometry. QM/MM refinement revealed a hydrogen-bond network involving Asp34, Asp216, the scissile peptide region, and several water molecules. An exploratory one-dimensional relaxed scan along the O(water)···C(carbonyl) coordinate showed that progressive water approach is associated with a moderate energetic cost. These results provide an atomistic multiscale model of the pre-reactive Chn/κ-CN complex and identify structural features that may contribute to substrate recognition and catalytic organization in bovine chymosin.

Abstract: Loperamide is an inexpensive μ-opioid receptor (MOR) agonist whose central action is normally restricted by low systemic exposure and ATP-binding cassette subfamily B member 1 (ABCB1/P-glycoprotein) efflux. Its major metabolite, N-desmethyl loperamide (dLop), is an informative matched molecular pair: dLop retains high MOR affinity but inhibits hERG less potently than loperamide, while remaining strongly effluxed and retaining other liabilities. We propose that the scaffold can be redesigned only if four overlapping maps—MOR function, ABCB1 transport, cardiac ion-channel inhibition, and developability—are measured separately and then recombined. Ten modification axes are analysed, with their evidence, favourable and adverse consequences, interaction logic, and synthetic burden. Single-variable pairs establish attribution; higher-order candidates combine only validated, non-redundant modules. We also compare original-plus-original, modified-plus-original, and modified-plus-modified products, while rejecting transporter or metabolic inhibition as a shortcut to brain exposure. Case reports of dependence, withdrawal-motivated misuse, malignant arrhythmia, and death motivate a co-primary abuse-liability programme and layered prevention strategy. The lowest-complexity programme is a dLop-centred, common-intermediate platform that first combines one safety module, one disposition module, and, only when justified, one efficacy-shaping module. The framework fails if improved central exposure or cardiac selectivity cannot be separated from lost MOR function or from respiratory, behavioural, gastrointestinal, addiction-related, and cardiac toxicity.

Abstract: Inspired by the newly discovered sandwich D_5d [Os(η⁵-B₅H₁₀)₂] as a carbon-free analog of ferrocene [Fe(η⁵-C₅H₅)₂] (Science 392, (2026): 411) and based on extensive global searches and first-principles theory calculations, we present herein the viable possibility of a staggered sandwich bis(η⁶-cycloborane)chromium D_6d [Cr(η⁶-(BH)₆H₆)₂] (1) with two equivalent η⁶- (BH)₆H₆ ligands isovalent with benzene as the boron analog of the eclipsed bis(η6-benzene)chromium D_6h [Cr(η⁶-C₆H₆)₂] (2). Detailed coordination bonding pattern, energy decomposition, and magnetically induced ring current analyses indicate that D_6d 1 matches the 18-electron rule (1S²1P⁶1D¹⁰) and exhibits similar aromaticity with D_6h 2, rendering high stability to the system. The metal-ring coordination bonding in D_6d 1 is dominated by effective Cr → (η⁶-(BH)₆H₆)₂ δ-back-donations which appear to be significantly stronger than the corresponding Cr → (η⁶-C₆H₆)₂ δ-back-donations in D_6h 2, leading to an unusually short ring-ring distance of 2.70 Å and large HOMO-LUMO gap of 7.06 eV in 1. D_6d 1 and D_6h 2 can also be used as building blocks to form their sandwich tetramers D_2h [Cr₄(BH)₄₈H₂₈] (3) and D_2h [Cr₄C₄₈H₂₈] (4) and sandwich two-dimensional nanosheets [Cr(η⁶-(BH)₆)₂] (5) and [Cr(η⁶-C₆)₂] (6) via partial or complete dehydrogenations, respectively.

Abstract: The development of lanthanide-based molecular magnetic materials incorporating organic radicals requires a fundamental understanding of how ligand modification influences magnetic exchange interactions while preserving the coordination environment around the metal center. In this predictive computational study, the electronic structures and magnetic properties of two hypothetical gadolinium(III) complexes with donor–acceptor semiquinone–nitronylnitroxide biradicals, Tp₂Gd(SQNN) (1) and Tp₂Gd(SQPhNN) (2), were investigated using SA-CASSCF/NEVPT2 calculations and compared with the previously characterized monoradical complex Tp₂Gd(SQ). The inclusion of dynamic correlation at the NEVPT2 level was essential for correctly predicting the antiferromagnetic nature of the Gd³⁺–biradical interaction, whereas SA-CASSCF alone yielded a ferromagnetic ground state. The computed exchange interaction between Gd³⁺ and the biradical in complexes 1 and 2 (J ≈ –2.6 cm⁻¹) is approximately two times weaker than that in Tp₂Gd(SQ) (J = –5.4 cm⁻¹). The intraligand exchange parameters JSQ–NN = 679.1 cm⁻¹ and JSQ–PhNN = 71.0 cm⁻¹ reflect strong ferromagnetic coupling within the biradical moieties. Application of the valence bond configuration interaction model yielded electronic coupling matrix elements HDA of 15283 cm⁻¹ and 6546 cm⁻¹ for the yttrium analogues of 1 and 2, respectively. The calculated magnetic susceptibility data for complexes 1 and 2 closely resemble the behavior of Tp₂Gd(SQ), although the characteristic temperatures differ due to the unequal exchange coupling strengths. This study demonstrates that modern computational methods enable reliable prediction of the key magnetic characteristics of heterospin systems based on their possible molecular structures.

Abstract: Theоretical methоds are indispensable in studying phоtоcatalytic reactiоn pathways, the energy barriers оf each elementary reactiоn step and in elucidating the active sites in catalysis. Transitiоn metal sulfides оf the 3d elements, M = Fe, Cо, Ni, Cu, mimic natural reductase and carbоn mоnоxide dehydrоgenase enzymes. The exact envirоnment оf enzyme centers, which includes a prоtein surrоunding the active site and cооrdinated ligands, cannоt be achieved by synthesis. Careful mоdeling оf ligands cооrdinated tо the active site can predict whether phоtоactivatiоn оccurs and the ways tо enhance visible light absоrptiоn. Fоr heavier transitiоn metals, such as the f-blоck elements, the phоtоphysical prоperties becоme mоre prоnоunced. Frоm the cоmputatiоnal results, suppоrted by experiments, sulfur emerges as a key element in prоmоting phоtоchemical and phоtоphysical activity. Bridging sulfur in the clusters and cоmplexes оf the 3d elements (M2-S2) acts as an electrоn-dоnоr similar tо cооrdinated carbоnyl оr nitrоsyl ligands. Lanthanides alsо take advantage оf the cооrdinatiоn оf sulfur-cоntaining ligands tо fine-tune light absоrptiоn and light-emissiоn, prоducing lanthanide sulfide phоtоcatalysts оr high-intensity luminescent cоmplexes. The excited-state energy transfer mechanism and factоrs respоnsible fоr the specific lanthanide emissiоn are successfully predicted by cоmbined DFT/TDDFT, multireference and semiempirical calculatiоns in clоse cоrrelatiоn with experiment.

Abstract: In the Heikal Universal Theory of Selective Interfaces and Spatial Resonance natural boundaries, called Selective Interfacial Manifolds (Barzakh), mediate interactions in macroscopic, biological, chemical, nuclear, and quantum systems. Conventional scientific and cosmological systems, are largely dependent on just mechanical measuring instruments, along with seeming dimensions, to narrate the behaviors of matter and energy. This dependency places basic methodological limitations, which cannot consider into complex systems, and interfacial phenomena. To overcome this limitation, we present here The Heikal Theory of Topological Selective Interfacial Manifolds a universal theoretical/mathematical model that dictates all reactive endeavors, be they chemical, physical, geological or the like – rethinking interaction, scattering and -equilibrium on cosmological, microscopic and quantum scales of -orders – including those of double orders. This is based on a sound mathematical structure with well-defined topological metric tensors (G_μν -Barzakh), scattering S_matrix, geometric resistance coefficients (Λ_T), diagnostic resonance criteria (R_lock), and indices of topological transformation efficiency ηHeikal. This paradigm-level manifestation shows that all the manifestations of formation of objects, flow of matter and energy, and spatial regularity of the universe are controlled not by simple volumetry but by nano- and cosmic-scale Selective Interfacial Manifolds which serve as topological bridges and states of topological tension connecting different domains of any category of interaction. By treating astrodynamics, interfacial interactions, scattering amplitudes, and structural transitions under different boundary conditions the theory provides a unified mathematical treatment of the most ultra-efficient topological confinement states, as well as structural collapse mechanisms under oxidative stress. Therefore, this approach establishes the basis for a universal scientific model beyond classical disciplinary boundaries which might gain insights into a geometric unification of the cosmos from minute particles to gaping the vastness of outer space as shown in Figure 1.

Abstract: The electrocatalytic reduction of CO₂ (CO2RR) into value-added chemicals represents a promising strategy for achieving carbon-neutral energy conversion. However, it is fundamentally limited by sluggish reaction kinetics, insufficient product selectivity, and the competitive hydrogen evolution reaction (HER). Herein, density functional theory (DFT) calculations were employed to systematically investigate transition-metal single-atom catalysts anchored on boron and nitrogen co-doped graphene (TM@BNG), with the aim of elucidating the role of heteroatom-induced coordination engineering in modulating catalytic performance. The results demonstrate that B, N co-doping effectively tailors the electronic structure of the metal active sites, thereby optimizing the adsorption energetics of key intermediates and dictating the reaction pathways. Among the 27 candidates examined, Pd@BNG, Ag@BNG, Sc@BNG, Cu@BNG, Co@BNG, Cd@BNG, and Y@BNG exhibit superior catalytic activity and selectivity toward CO or HCOOH production, featuring low limiting potentials down to −0.06 V while simultaneously suppressing HER. Mechanistic analysis reveals that product selectivity is governed by the relative stabilization of *COOH and *HCOO intermediates during the initial proton-coupled electron transfer step. Furthermore, a physically interpretable descriptor (φ), constructed via machine-learning approaches based on intrinsic electronic properties, establishes a volcano-type correlation with the limiting potential, thereby enabling quantitative prediction of catalytic activity. Collectively, these findings elucidate the electronic-structure modulation of single-atom catalysts and establish a generalizable framework for the rational design of high-performance CO₂RR electrocatalysts.

Abstract: Counterion-deficient liquid states are formulated within a solvent-general framework for charge-selective forcing under rapid electrostatic relaxation. When the Maxwell relaxation time is short relative to the forcing or chemical timescale, persistent bulk space charge is not an admissible long-lived description: the liquid interior relaxes toward near electroneutrality, finite residual charge localizes predominantly at the interface, and the compensating opposite charge need not be stored as an ordinary dissolved counterion in the same phase. On that basis, two complementary forcing branches are developed. In the negative branch, low-entry-energy electron delivery reduces dissolved cations or plates neutral material by populating the lowest accessible acceptor manifold, leaving anion-rich dissolved states. In the positive branch, low-entry-energy noble-gas dications act as formally universal two-electron scavengers that remove electrons from the highest available occupied density, including solvated-electron populations, lone-pair-rich molecular donors, and halide anions. A solvent-general admissibility window is derived in terms of entry kinetic energy, Maxwell relaxation, interfacial field, Rayleigh stability, leakage time, and heat-removal capacity. From these constraints, explicit operatingcurrent bounds are obtained, and an illustrative aqueous benchmark shows how Rayleigh, dielectric, and thermal limits separate in practice. Water, electron-solvating media such as calcium in tetrahydrofuran, and halide-containing liquids such as LiCl in tetrahydrofuran serve as representative realizations. The framework therefore yields predictive bookkeeping relations, dimensionless admissibility parameters, a noble-gas dication energy ladder, operational current ceilings, and experimentally falsifiable signatures that distinguish counterion-deficient chemistry from ordinary dissolved countercharge compensation.

Abstract: This paper investigates the application of the Symbolic Difference Structure (SSD) method as an innovative tool for multidimensional analysis and classification of elements in the periodic system. By applying the SSD algorithm (\(k=3\)) to five key physicochemical properties—atomic mass, electronegativity, first ionization energy, number of unpaired electrons, and melting point—the study demonstrates that the periodic system exhibits a recognizable numerical geometry that can be systematically quantified. The results show that SSD classification does not alter established chemical periodicity but enables: (1) quantitative discrimination between genuine nuclear anomalies and metrological artifacts, (2) identification of characteristic “hotspots’’ where multiple properties change simultaneously, and (3) a heuristic framework for predicting properties of heavy and superheavy elements. The analysis is extended using monoisotopic masses and correlation studies, confirming the diagnostic value of the method and opening new pathways for comparative analysis in materials science and chemical education.

Abstract: We present D2BIA_discrete, a zero-cost computational framework for predicting local aromaticity in linear acenes without quantum chemical calculations. The model partitions π-electron density using a 61/39 localized/delocalized ratio derived from spin-coupled valence bond and QTAIM analyses, combined with Slater-type orbital decay to estimate ring-center electron density. Three progressive refinements introduce molecular topology weighting, tunable bond-sharing (α), and depth-dependent attenuation (γ) parameters. Leave-one-n-out cross-validation on benzene through undecacene yields optimal parameters α=1.00 and γ=0.05, achieving ring-by-ring predictions with R²=0.456 and RMSE=2.394×10⁻³ against fluorescence aromaticity index (FLU). Model 2 provides excellent molecular-averaged correlations (R²>0.93 for FLU, PDI, HOMA) and reliable ring-level predictions for terminal and first internal rings. Local LONOCV D2BIA_discrete has excellent metrics with six-center index (R² = 0.922, R = 0.960, RMSE = 0.219, MAE = 0.139, MRE = 4.83%), showing importance of zero-cost D2BIA_discrete to obtain local aromaticity of linear acenes in agreement with SCI gradients for the same group. This is our third work based on the so-called discrete geometry chemistry.

Abstract: The review presents the first attempt to build the virtual world of free-radical polymerization of vinyl monomers itself and in the presence of small additives of stable radicals in due course of extended virtual experiment. Chain-reaction essence of the chemical process; quantum-chemical concept of elementary reactions; spin theory of radicals; and digital-twin of their presentation lay the foundation of the world formed, which opens a new vision of the role of IT technologies for the virtualization of various chemical processes

Abstract: This review presents the covalent chemistry of carbon within the spin-radical concept of electron interaction. Using the language of valence bond trimodality, the regions of classical spinless covalence and its spin counterpart are defined. Carbon is the only element exhibiting spin covalent chemistry. Classical covalent chemistry of carbon concerns molecular substances whose valence bond structure includes segregate or chained single sp3C-C bonds. Substances with double sp2C=C and triple sp1C≡C bonds are the subject of spin covalent chemistry of carbon. The mathematical apparatus of spin covalence forms the basis of algorithms governing the chemical modification of carbon substances, polymerization processes, and catalysis involving them, making it possible to supplement the empirical spin covalent chemistry of carbon with its virtual analog.

Abstract:

This computational study investigates the thermal decomposition of 1,2,4-triazol-3(2H)-ones and their thione analogues using Density Functional Theory (DFT). The reaction proceeds via a concerted, six-membered cyclic transition state, primarily driven by the breaking of the N–N bond. A key finding is that the accuracy of the calculated activation energies (Ea) strongly depends on the choice of the DFT functional. For sulfur-containing systems (thiones), the hybrid functional APFD (with 25% Hartree-Fock exchange) provides the most reliable results, effectively describing their higher polarizability. In contrast, for oxygen-containing systems (triazolones), the dispersion-corrected functional B97D-GD3BJ (with 0% Hartree-Fock exchange) delivers superior accuracy by better modeling electrostatic and dispersion interactions. The -CH₂CH₂CN group at the N-2 position acts not only as a protecting group, but also stabilizes the transition state through non-covalent interactions. Electron-withdrawing substituents slightly increase the Ea, while electron-donating groups decrease it. Sulfur analogues consistently show significantly lower activation energies (by ~40 kJ/mol) than their oxygen counterparts, explaining their experimentally observed faster decomposition. This work establishes a dual-methodology computational framework for accurately predicting the kinetics of these reactions, providing valuable insights for the regioselective synthesis of biologically relevant triazole derivatives via controlled pyrolysis.

Abstract:

Tuberculosis, caused by Mycobacterium tuberculosis (M. tb), remains a leading global threat, escalated now by the rise of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains. In search of a novel anti-tubercular agent with a distinct mechanism of action, this study explores deep-sea marine metabolites as potential inhibitors of the F₄₂₀-dependent oxidoreductase Rv1155, a redox enzyme essential for M. tb survival. A total of 2,773 marine-derived compounds curated from the CMNPD, Reaxys, and MarinLit databases were screened using an integrated CADD workflow combining molecular docking, in-silico ADMET profiling, and molecular dynamics (MD) simulations. Docking results revealed several metabolites with high affinity for the Rv1155 binding pocket, and three compounds: Upenamide (CMNPD_22964), Aspyronol (Compound_1749), and Fiscpropionate F (Compound_1796) as hit candidates. Among these, Upenamide displayed the strongest binding and stable protein-ligand dynamics, while Aspyronol demonstrated a promising ADMET profile comparable to that of the native cofactor F₄₂₀₂. These findings highlight the potential of deep-sea marine metabolites as a valuable source of anti-tubercular scaffolds and establish a computationally driven, cost-effective framework for discovering inhibitors targeting F₄₂₀-dependent enzymes. This approach provides a foundation for future experimental validation and expansion to additional F₄₂₀-related drug targets in M. tb.

Abstract:

The reactions of formaldehyde oxide (CH2OO) with methane and ethane that yield alcohol products were investigated using dual-level variational transition state theory with multidimensional tunneling corrections (VTST/MT). Additional systems—including halogenated formaldehyde oxides (CF2OO and CCl2OO), deuterated alkanes (CD4, C2D6), and isotopically substituted formaldehyde oxide (CH218O18O)—were also examined to explore substituent and isotope effects. Bimolecular rate constants and kinetic isotope effects (KIEs) were computed over the temperature range of 100–600 K. Significant tunneling contributions were predicted, especially below room temperature, where tunneling increases the rate constants of the CH2OO + alkane reactions by up to two orders of magnitude. The computed H/D KIEs are approximately 3 at 300 K and rise to ~10 at 200 K. Notably, pronounced oxygen tunneling was also observed, giving 18O KIEs of ~1.2 at 300 K and ~2.2 at 200 K. Halogen substitution was predicted to substantially reduce reaction barriers due to the weakening of the O–O bond, leading to rate constants for CF2OO reactions that exceed those of CH2OO by more than ten orders of magnitude at 300 K. The mechanisms underlying the strong tunneling effects, the individual contributions to the calculated KIEs, and the implications of these findings for atmospheric chemistry are discussed.

Abstract: Due to their chemical structure and convenient, tunable physicochemical properties, intermetallic alloys and materials are promising for use in various fields, such as gas sensors. The aim of this study was to perform DFT GGA calculations of the adsorption energy of atomic nitrogen and the properties of partially substituted metal atoms with nitrogen in Ti3Sb supercells with an A15 cubic structure. Adsorption and doping at various adsorption sites and crystallographic orientations (110; 111; 100), as well as their electronic properties, were studied in 2 × 2, 3 × 3, and 5 × 5 supercells. The density of states (DOS) of Ti3Sb–N supercells with two different positions of partial substitution of nitrogen for Ti3Sb metal atoms was calculated: N/Ti and N/Sb. Comparative data show that the structural and energetic properties of Ti3Sb–N vary compared to pure Ti3Sb. Controlled incorporation of nitrogen atoms and partial substitution of Ti3Sb atoms allow for tuning of the properties of Ti3Sb–N. These data can be used to optimize and predict the electronic structure and response characteristics of such materials for electronics and catalysis. They are also important as potential sensor materials with exceptional properties and promising applications for nitrogen detection in targeted developments.

Abstract: Electronegativity is a cornerstone of chemical theory, yet its traditional definitions remain empirical. Here, a variational definition of electronegativity (\( χ_V \)χ_V) is proposed, derived directly from the principle of least action. In this framework, the ratio between the effective nuclear charge (Z_eff\( Z_eff \)) and the principal quantum number (\( n^* \)n*) quantifies the deviation of an atom from its stationary (minimal-action) configuration, yielding \( \) χ_V=κ[(Z_eff/n* )²-1] , with a single universal constant (κ) fixed using fluorine. The scale reproduces periodic trends without empirical fitting and shows strong linear correlations with Pauling, Mulliken, and Allen electronegativities (r = 0.91–0.97, R² ≈ 0.9). χ_V also exhibits a nearly perfect proportionality with the first ionization energy (r = 0.9999) and an inverse-square dependence on atomic radius (R² = 0.904). When applied to 47 diatomic molecules, predicted bond-dissociation energies yield a mean absolute error of 15.8 kJ mol⁻¹—slightly lower than Pauling’s classical relation. These results demonstrate that electronegativity can be interpreted as a quantified deviation from the condition of least action, bridging atomic structure, energy, and reactivity within a unified physical framework.

Abstract: A unified electromagnetic response theory has been formulated in terms of quasi-energy derivatives within the nonrelativistic single-determinant framework. The formalism is applicable to both optical and non-optical electromagnetic responses, without restriction to monochromatic fields. Electromagnetic properties are expressed through quasi-energy derivatives, providing a consistent and general description under arbitrary static or dynamic perturbations. Magnetic properties obtained from this framework are inherently gauge-invariant, since a gauge transformation of the electromagnetic potentials corresponds to a unitary phase transformation acting on both the Hamiltonian and molecular orbitals. The present theory thus offers a comprehensive foundation for evaluating (hyper)polarizabilities, (hyper)magnetizabilities, and other related response properties.

Abstract: Machine learning is rapidly reshaping the field of chemical synthesis, influencing how chemists design, plan, and carry out reactions. Yet for many students, the role of artificial intelligence in synthesis remains abstract or inaccessible. This article introduces the current landscape of machine learning in chemistry, focusing on why these new approaches are emerging and how they complement, rather than replace, human creativity. We outline the challenges of traditional retrosynthetic planning, describe the rise of AI-driven platforms such as IBM RXN and AiZynthFinder, and discuss how they exemplify broader changes in the practice of chemistry. Practical “try it yourself” suggestions are included to help students and educators explore these developments firsthand. By highlighting both opportunities and limitations, this guide equips learners to critically understand the future of synthesis as a collaboration between chemists and computational tools.