Targeted delivery of the chemotherapeutic 2-mercaptopyridine (2-MP) requires robust carriers to mitigate rapid systemic degradation. Because pristine carbon nanotubes (CNTs) exhibit weak drug retention, this study investigates transition-metal-doped (Co, Sc, Ru, V) CNTs as dual-action nanocarriers and electrochemical sensors. While pristine CNTs display weak physisorption with adsorption energy E_ads= -36.52 kcal/mol, transition-metal doping induces robust coordinate covalent chemisorption. Ru-doped CNTs exhibit optimal thermodynamic stability with E_ads= 43.56 kcal/mol and extended gas-phase drug retention with recovery time τ =828 s, preventing premature payload leakage. Conversely, in competitive aqueous media, these functionalized carriers facilitate rapid, diffusion-controlled release. Furthermore, 2-MP encapsulation triggers a highly sensitive 34.32
Bowman-Birk inhibitors (BBIs) are cysteine-rich proteins that inhibit trypsin and chymotrypsin proteases. Derived from soybeans, these natural BBIs have been identified as potential anticarcinogenic agents. Recent studies of the black-eyed pea trypsin/chymotrypsin inhibitor (BTCI) demonstrated that peptides derived from the BBI family may retain their structure and inhibitory activity. Therefore, this study aimed to investigate the effects of solvent on BTCI-derived peptides and their inhibitory activity against trypsin. The results show that cyclic peptides exhibit reduced conformational flexibility, enhanced reactivity (narrower HOMO–LUMO gap), and LUMO localized at the disulfide bonds, in contrast to the linear peptide Ptry6. Non-covalent interactions were evaluated using the Independent Gradient Model based on Hirshfeld partitioning (IGMH). Molecular electrostatic potential maps and the IGMH confirmed that the cyclic architecture concentrates electropositive donor regions at key residues (Thr2, Lys3, Ser4, and Ile5), whereas Ptry6 displays only weak van der Waals contacts. Docking studies against trypsin showed strong hydrogen-bond and electrostatic interactions between cyclic peptides and residues involved in the catalytic mechanism. Predicted inhibition constants obtained from docking studies closely match experimental data. These findings suggest that electronic redistribution upon solvation governs peptide–trypsin affinity, highlighting Ptry9L as the most promising BTCI-derived inhibitor for further biotechnological development. BTCI peptides were studied using quantum-chemical calculations and molecular docking. Three peptides—a cyclic nonapeptide in both L- and D-configurations (Ptry9L, Ptry9D) and a linear hexapeptide (Ptry6)—were optimized in vacuo and in implicit aqueous solvent using density functional theory at B3LYP-D3/Def2-SVP and B3LYP-D3/6-311+G(d,p) levels with D3 dispersion correction. Frontier molecular orbital analyses (HOMO–LUMO gaps and orbital localization) and IGMH revealed that the disulfide bond stabilizes cyclic peptides.
Hybrid organic–inorganic chalcogenides have emerged as promising multifunctional materials due to their structural flexibility and tunable physical properties, making them attractive candidates for energy-conversion, optoelectronic, environmental, and radiation-protection technologies. In this study, the structural, electronic, mechanical, optical, thermodynamic, radiation-shielding, and hydrogen-storage properties of CH3NH3MnS3 were comprehensively investigated. The optimized structure exhibits excellent stability, while mechanical analysis confirms elastic stability and anisotropic behavior. Optical calculations reveal strong absorption across the visible and ultraviolet regions, accompanied by a high dielectric response, moderate refractive index, and low reflectivity, indicating suitability for photovoltaic and photodetection applications. Dynamical and thermal stability are verified through phonon-dispersion and thermodynamic analyses. Radiation-shielding calculations demonstrate efficient attenuation of low-energy photons with small half-value and tenth-value layers. Furthermore, hydrogen-storage investigations predict favorable adsorption energetics, a gravimetric storage capacity of approximately 13.2 wt. 1 E(V)=E_0+9/16B_0V_0[(V_0/V)^2/3-1]^2[1+3/4(B_0^/-4)(((V_0/V)^2/3-1)] In the Birch–Murnaghan equation of state, E(V) represents the total energy of the compound at a given unit-cell volume V, while E0 is the minimum equilibrium energy. V0 denotes the equilibrium unit-cell volume corresponding to the most stable structure. B0 is the equilibrium bulk modulus, which measures the resistance of the material to compression, whereas B0′ represents the pressure derivative of the bulk modulus and describes how the compressibility changes under pressure. The term (V0/V)2/3 describes the relative change in volume with respect to the equilibrium volume. By fitting calculated energy–volume data to this equation, the equilibrium structural and mechanical parameters of the investigated compound can be obtained.
We theoretically study the excitonic properties in semiconductor transition metal dichalcogenide monolayers (ML-TMDs)(WSe _2 , WS _2 , MoSe _2 , MoS _2 , and MoTe _2 ) encapsulated in hexagonal boron nitride (hBN). Excitonic binding energies and full non-hydrogenic Rydberg series (s, p, and d states) are calculated. As a first validation, the binding energies of the 1s-5s states of WSe _2 /hBN are reproduced to less than 2 meV ( <1% ) over the entire range of thicknesses N ∈ [0,∞ [ , and the separation Δ _12= 127.8 meV reproduces the experimental value without adjusted parameters. We further derive a generalized two-sided dielectric potential V(r, N_top, N_bot) that captures the asymmetric encapsulation geometry, and compute the two-dimensional map E_b(N_top,N_bot) for WSe _2 . A new analysis of Coulomb engineering shows that E _b (1s) varies by up to a factor of three across experimentally accessible dielectric environments, while the ratio E_b(2s)/E^b(1s) serves as a sensitive probe of the non-hydrogenic character. Moreover, Berry-curvature corrections lift the angular-momentum degeneracy of p-and d-type excitons by 2–8 meV, with M-based compounds showing larger effects. Finally, the quadratic Stark polarizability under an out-of-plane electric field is computed via exact s-p coupling, with results depending sensitively on N and the material parameters. These results provide a unified quantitative framework directly applicable to studies on van der Waals heterostructures. The generalized Rytova-Keldysh (RK) Schrödinger equation is solved using a cell-centered finite-difference scheme on a fine real-space grid (N = 2000 points, ξ _max = 50), with the calculations incorporating both Coulomb engineering effects and an applied out-of-plane electric field. Topological Berry phase corrections are subsequently introduced: the differential Berry curvature between the conduction and valence bands computed within the bulk Dirac model is averaged over the exciton momentum distribution through a Bessel-Hankel transform, yielding an energy shift that scales linearly with the azimuthal quantum number m.
The [H3O(H2O)3]+Cl− ion-pair is the smallest cluster of ionized HCl in water. It has been demonstrated experimentally that it can be formed in conditions compatible with the interstellar medium (ISM). It is also a precursor of another ion-pair, H3O+(MetOH)3Cl−, suggested as an important prebiotic species in the ISM. Aiming to help the detection of the former ion-pair several properties of its n-3 s and n-3p singlet and triplet Rydberg states have been studied through a highly correlated ab-initio method. The vertical excitation energies (ΔEv), oscillator strengths (f), dipole moments (μ), diradical character, participation ratio of natural transition orbitals (PRNTO), single-excitation character (Ω), charge-transfer numbers and the singlet–triplet gaps (ΔEST) have been studied at the ground state (gs) geometry. The energies of the two lowest-lying dissociation channels have also been computed. Our highest-level results for ΔEv of the n-3 s singlet states are between 6.63 and 6.65 eV, while for n-3p one has 7.40 to 7.74 eV. Previous TD-DFT results are 0.84 to 0.95 eV lower, but our results nicely agree with available CASPT2 results for the n-3 s states. The brighter state is the 2nd n-3 s state, with f = 0.172 at the highest-level. While the gs is essentially a closed-shell state, consistent with the [H3O(H2O)3]+Cl− ion pair, all n-3 s and n-3p singlet states have high diradical characters, consistent with their small ΔEST values and with their nature as charge-recombination (CR) states. For most of the cases the CR characters are consistent with a decrease of μ. A possible deactivation pathway for the n-3 s states, involving their optimized geometries and a four-states conical intersection, is discussed. Our highest-level results yield the ionic channel 0.46 eV lower than the neutral channel. Ω indicates dominant single-excitation character for all Rydberg states, while PRNTO indicates multi-configurational character only for few n-3p states. The multi-reference configuration interaction with singles and doubles (MR–CISD) calculations (including size-extensivity corrections) have been employed. Size-extensivity corrections have only been applied for ΔEv and for the energies of the dissociation channels. f, μ and ΔEST have been computed from the MR-CISD wavefunctions. PRNTO, Ω and the charge-transfer numbers (from which the nature of the excited states in terms of local, charge-transfer or CR states are obtained) have been computed from the one-electron transition density matrix. Three basis sets have been employed. The smallest one is the Pople’s 6–31+ +G**, while the second one is a mixed basis set based on the aug-cc-pVDZ and the dʹ-aug-cc-pVDZ (a reduced d-aug-cc-pVDZ basis set). The third one is also a mixed basis set, consisting of the aug-cc-pVDZ and the universal Rydberg basis set of Kaufman et al. The possible deactivation pathway for the n-3 s states has only been studied at the MR-CISD level with the smallest basis set.
Coumarin and its derivatives are privileged scaffolds in medicinal chemistry, yet their polymorphism poses significant challenges in pharmaceutical solid-form development. This work explores the crystal polymorphs and optoelectronic properties at ground state of coumarin. The crystal energy landscape of coumarin was constructed, identifying P43, Pccn, and P42bc as the dominant competing polymorphic structures. Electronic structure calculations reveal that the symmetry of crystal packing and intermolecular interactions significantly modulate the optical absorption edge and spectral response range, with the P43 phase exhibiting the smallest band gap (2.69 eV) due to its unique helical packing arrangement. Crystal structures were generated using the PyXtal library across 230 space groups. High-throughput geometric optimization was performed using the universal machine learning interatomic potential DPA-3. Low-energy candidate structures were further refined via density functional theory (DFT) calculations using the Quantum ESPRESSO package with the PBE functional and DFT-D3 dispersion correction. Optical properties were derived from the complex dielectric function computed from first principles.
The widespread application of crumb rubber modified asphalt is limited by its inadequate storage stability, which is largely governed by the compatibility between the asphalt binder and crumb rubber. This study investigated the influence of desulphurized crumb rubber with different solubility on the compatibility and storage stability of modified asphalt by combining molecular simulations with experimental validation. The results demonstrate that the compatibility between desulphurized crumb rubber and asphalt is strongly dependent on solubility when the difference in solubility parameter exceeds approximately 1.5 (J·cm⁻3)1/2. Desulphurized crumb rubber with a solubility of approximately 28.66 exhibited the highest interfacial binding energy, reduced phase separation, and improved storage stability, whereas excessive desulphurization decreased interfacial binding energy and increased the tendency for phase separation. Molecular dynamics (MD) simulations and density functional theory (DFT) calculations were performed using Materials Studio 2023. MD simulations were carried out with the Forcite module using the COMPASS III force field. Following geometry optimization and annealing, the systems were equilibrated under the NPT and NVT ensembles, and the solubility parameter, interaction energy, mean square displacement, and fractional free volume were calculated. DFT calculations were performed using the DMol3 module with the BLYP functional within the generalized gradient approximation (GGA) to investigate the intermolecular interactions. Desulphurized crumb rubber with different solubility was prepared by a twin-screw extrusion process, and the simulation results were validated using the separation softening point difference and multi-stress creep recovery (MSCR) tests.
Monte Carlo (MC) simulations reveal that diblock copolymer nanoparticle morphology is dictated by the interplay between intermolecular attractions and soft confinement. Blocks with stronger cohesive interactions undergo local densification in the core, while blocks with weaker interactions localize at the surface. A key stabilizing mechanism is the expulsion of high-mobility end-monomers toward the interface to maximize cohesive energy in the bulk. This process is accompanied by a backbone gauche-to-trans conformational transition that enables polymer chains to flatten tangentially and adapt to nanoparticle curvature. By quantifying radial density profiles, structural anisotropy, and energetic oscillations, the methodology distinguishes morphologies ranging from surface-energy-driven mixing to frustrated core–shell segregation, providing molecular-level insight for the rational design of functional polymeric nanostructures. MC simulation of the coarse-grained (CG) models based on “polyethylene-like” chains mapped onto the second nearest neighbor diamond (2nnd) lattice was employed to investigate conformational and structural properties of diblock copolymer nanoparticles. The model integrates a revised Rotational Isomeric State (RIS) model to define backbone bond conformations and discretized Lennard–Jones (LJ) potential energy settings to systematically vary intermolecular interaction parameters. Free-standing nanoparticles were equilibrated using single bead moves and the Metropolis criterion over 40 million Monte Carlo steps, and data analysis was based on snapshots collected at intervals of 10,000 MCS. All simulations and data analysis were performed using in-house FORTRAN codes with the gfortran compiler.
Organic light-emitting materials based on tris(8-hydroxyquinoline) aluminum (Alq₃) and gallium (Gaq₃) remain benchmark emitters in OLED research due to stable emission behaviors. The present work is concerned with the molecular and optical characteristics of these compounds by introducing CH/N substitutions at different positions. A series of derivatives was constructed to evaluate the impact of structural modifications on absorption, emission, and Stokes shift. The results reveal that substitution position apparently affects electronic transitions and spectral behavior. Modifications on the pyridyl side tend to induce red shifts, whereas those on the phenoxide side result in blue shifts. Molecular orbital analyses further indicate that parent complexes exhibit multi-orbital excitations, whereas the 5n₂p derivatives show localized HOMO to LUMO + 1 transitions, leading to higher excitation energies and narrower Stokes shifts. Molecular structures were constructed using GaussView and subsequently optimized by density functional theory (DFT) with the B3LYP functional and the 6-31G(d) basis set. The first singlet excited-state (S₁) geometries were optimized using the CIS method with the 3-21G* basis set. Then, based on the optimized ground- and excited-state structures, the absorption and emission spectra were obtained at the B3LYP/3-21G* level from time-dependent DFT (TD-DFT). All calculations were carried out using the Gaussian software package. The computed results have a good agreement with the experimental UV–vis and photoluminescence trends, providing confidence in the modeling approach.
A theoretical investigation of 28 homoleptic Cu(I) complexes was conducted to assess their suitability as sensitizers in dye-sensitized solar cells (DSSCs). Two ligand families, triazolylpyridine (G1) and imidazopyridine–pyridine (G2), were systematically functionalized with heteroaromatic substituents derived from pyridine, furan, pyrrole, and thiophene. Pyridine- and thiophene-based spacers produced substantial bathochromic shifts in the absorption maxima, which reached 492 nm, and reduced the HOMO–LUMO energy gaps to values as low as 3.33 eV. These modifications also decreased the chemical hardness (η) and increased the electrophilicity (ω), thereby promoting intramolecular charge transfer and enhancing electron-accepting ability. In contrast, furan- and pyrrole-derived substituents induced only minor electronic changes but increased the propensity to form dual-bidentate or multidentate adsorption motifs on TiO2 surfaces, resulting in stronger interfacial binding. An integrated DSSC index (Di), combining structural, optoelectronic, reactivity, and photovoltaic parameters, identified the G2 family as the most favorable structural framework, with G2ANNC (Di = 0.6096) emerging as the leading sensitizer candidate. Overall, these results demonstrate the potential of these Cu(I) complexes for DSSC applications and provide a systematic framework for their rational design. Minimum-energy geometries were determined in ethanol using the M06 functional, with the 6-31G(d) basis set for nonmetal atoms, the DZVP basis set for Cu, and the IEF-PCM solvation model as implemented in Gaussian 16. UV–Vis transitions and excited-state energies were calculated by TD-DFT at the same level of theory for 20 excited states. Electronic transitions were analyzed using AOMix, whereas hole − electron distributions and natural transition orbitals were evaluated using Multiwfn. Photovoltaic parameters, including the light-harvesting efficiency (LHE), excited-state lifetimes, and thermodynamic driving forces for electron injection, dye regeneration, and recombination, were quantified. Bulk anatase TiO2 and an expanded (TiO2)96 slab were optimized using the tiorg-0–1 and mio parameter sets in DFTB + 24.1. Slab reoptimization and dye–surface interactions were evaluated using GFN1-xTB at the Γ point. The candidates were globally evaluated and ranked using a custom Python script. Molecular and crystal structures were visualized using VESTA 3.90.5a.
Cellulose nanocrystals (CNCs) are a type of cellulose with excellent mechanical performance and other advantageous attributes. According to previous reports, hydrogen bonds play a pivotal role in the anisotropic structure of the CNC. Understanding the structure and mechanical behavior of CNC on a mesoscopic scale is critical for the development and manufacture of cellulose materials. However, experimental observations and atomistic simulations are not appropriate on the mesoscopic scale. In this study, we introduce an analytical coarse-grained (CG) potential following an extended bottom-up approach that is directly parameterized using reinforcement learning (RL). RL is a powerful tool for industrial and academic applications in various fields. Nevertheless, the potential of RL has not yet been fully exploited in the field of molecular dynamics. The RL and Boltzmann inversion methods were employed to develop a novel CG model of cellulose to represent its anisotropy and polymer stiffness. The resulting approximate CG model is not limited to the specific properties used for training; it can reproduce the dynamic mechanical properties under various conditions without further optimization. This model confirms that RL can construct a CG potential that is both physically interpretable and powerful. The training code is available at https://github.com/EiPiFun/rl-cll-cg . All atom (AA) reference molecular dynamics simulations were conducted using GROMACS with CHARMM36 force field, utilizing CHARMM-GUI tools to generate the necessary force field files. Coarse-grained (CG) simulations were performed using LAMMPS, employing a custom-defined explicit analytical force field. This potential consists of harmonic bonded interactions, 12–6 Lennard–Jones nonbonded interactions, and a modified 12–10 potential to account for directional hydrogen bonding. Initial estimates for bonded force constants were derived using the Boltzmann inversion method. The CG potential parameters were parameterized via a degenerate reinforcement learning (RL) approach employing the soft actor-critic (SAC) algorithm, implemented through the OpenAI Stable-Baselines3. To assess mechanical performance and model generalization, steered molecular dynamics techniques were utilized to simulate in-plane and out-of-plane fractures. For benchmarking purposes, baseline CG models were generated using the iterative Boltzmann inversion (IBI), relative entropy (RE), and force matching (FM) approaches via VOTCA, while the MARTINI 3 model was prepared using Polyply. Further validation of the optimization strategy was performed by comparing the RL approach against Tree-structured Parzen Estimator (TPE) and Covariance Matrix Adaptation Evolution Strategy (CMAES) algorithms using OPTUNA. All molecular structures were visualized using Open-Source PyMOL.
Chloride-containing species, H2O, and O2 are important environmental factors during the initial atmospheric corrosion of copper. In the present work, Cl− adsorption on Cu(111) was first investigated using a fully relaxed Cu model to characterize chloride-induced structural reconstruction and electronic activation. H2O and O2 were subsequently introduced to examine their additional co-adsorption effects on the chloride-affected Cu surface under simplified conditions representing humid and oxygen-containing environments. The introduction of Cl− induces pronounced local Cu-atom displacement, surface reconstruction, lattice distortion, and redistribution of the Cl-derived and Cu-derived electronic states. The subsequent addition of H2O and O2 further modifies the adsorption geometry and interfacial electronic environment. These results provide atomistic insight into chloride-induced surface activation relevant to the initial stage of copper corrosion, but they are not interpreted as direct proof of Cu dissolution or crystalline copper-chloride formation. Density functional theory calculations were performed using a three-layer, nonuniform Cu(111)-derived model containing 121 Cu atoms. Two structural-relaxation protocols were adopted according to the purposes of the calculations. For the initial Cl−/Cu(111) systems used to examine chloride-induced reconstruction, all Cu atoms and the Cl− species were allowed to relax without positional constraints. After the optimized Cl/Cu(111) configuration had been obtained, H2O and O2 were introduced sequentially. In the subsequent co-adsorption calculations, all adsorbates and the Cu atoms in the outermost layer were allowed to relax, whereas the lower two Cu layers were fixed. Optimized structures, relaxation-inclusive adsorption energies, Hirshfeld charge redistribution, work-function changes, interlayer displacements, total density of states, and projected density of states were analyzed to characterize the structural and electronic responses of the investigated systems.
Using the density functional theory (DFT) method, we studied the adsorption behaviour of different toxic quinone molecules, including anthraquinone (AQ), naphthoquinone (NQ), and pyrenequinone (PQ), on β-antimonide phosphorus (β-SbP) nanosheet. Initially, we ascertained the geometrical stability of β-SbP with the support of formation energy, phonon band maps, and ab initio molecular dynamics (AIMD). The electronic attributes of β-SbP are investigated using band structure and projected density of states (PDOS) maps, and the energy gap is calculated to be 2.265 eV. The adsorption of quinone molecules induces a relative band gap variation of 33 20 A in order to eliminate the field effect of neighbouring layers. Also, the thermal stability of β-SbP nanosheet under ambient conditions and at elevated temperatures of 400 K and 500 K is explored using ab initio molecular dynamics (AIMD) simulations.
Directional solute–solvent contacts can influence the electrostatic response of donor–acceptor chromophores, although such local effects are often represented only as averaged contributions in continuum solvent models. Quinolinylaminophenol (QMAP) in dimethyl sulfoxide (DMSO) was examined as an explicit first-shell microsolvation model to clarify how local solvent organization couples to QMAP conformation and dipolar response. The Car–Parrinello molecular dynamics trajectory indicates a geometric reorganization around 12–13 ps, accompanied by changes in the first-shell DMSO dipolar arrangement. Within the limitations of the finite microsolvated model, these results suggest that transient first-shell solvent organization contributes to the modulation of the local electrostatic environment of QMAP, rather than acting only as a static dielectric background. The gas-phase QMAP geometry was optimized at the CAM-B3LYP/6–311 + + G(d,p) level using Gaussian 16. The explicit QMAP–DMSO model contained one QMAP molecule and 21 DMSO molecules in a periodic cubic cell and was propagated by Car–Parrinello molecular dynamics using the CPMD code. The production trajectory was obtained with the PBE exchange–correlation functional, Troullier–Martins norm-conserving pseudopotentials, a plane-wave basis set, NVT equilibration at 300 K, and a restarted thermostatted CPMD production protocol, with a total analyzed trajectory length of approximately 32 ps. Structural, hydrogen-bond, dipole-moment, IR-like, and orientational-correlation analyses were carried out using in-house Python scripts.
Asphaltene aggregation and deposition pose major challenges in crude oil transport and processing. While extensive experimental studies have explored mitigation strategies, nanomaterials—particularly carbon nanotubes (CNTs)—have emerged as promising inhibitors due to their ability to adsorb asphaltenes and limit their clustering. However, experimental approaches provide limited insight into molecular-scale mechanisms. To address this, molecular dynamics (MD) simulations were performed to investigate interactions between model asphaltenes and CNTs in a toluene/heptane solvent. Five systems were studied: pristine CNTs and CNTs functionalized with carbamoyl (CONH2), methylcarbamoyl (CONHCH3), hydroxymethyl (CH2OH), and carboxylate (COO⁻) groups. Intermolecular interactions and aggregation behavior were analyzed using radial distribution functions (RDF), solvent-accessible surface area (SASA), cluster analysis, hydrogen bonding, and interaction energy decomposition (van der Waals and electrostatic contributions). Results show that CNTs significantly modify asphaltene aggregation, with carboxyl-functionalized CNTs exhibiting the strongest inhibition effect. This performance correlates with enhanced specific interactions between functional groups and asphaltene molecules, leading to reduced aggregation. Geometry optimizations and vibrational frequency calculations of toluene, heptane, the model asphaltene molecule, and the pristine carbon nanotube were performed using the Gaussian software package. These calculations were carried out within the framework of density functional theory (DFT) using the B3LYP functional and the 6-31G(d,p) basis set. The optimized structures obtained were subsequently used to construct the initial configurations for the molecular dynamics simulations and to derive Mulliken atomic charges for force-field parameterization. All-atom molecular dynamics simulations were performed using GROMACS 2023.3 and the OPLS-AA force field. After energy minimization using the steepest descent algorithm, the systems were equilibrated under NVT and NPT ensembles at 298.15 K and 1 bar. Production simulations were subsequently carried out for 150 ns using periodic boundary conditions and a 2 fs integration time step. Temperature and pressure were controlled using the velocity-rescaling thermostat and the Berendsen barostat, respectively. Long-range electrostatic interactions were treated using the Particle Mesh Ewald (PME) method, while bond constraints were maintained using the LINCS algorithm.
The tautomerization of thymine between its keto and enol forms is a key event for spontaneous mutagenesis. While the intrinsic enol-to-keto conversion is kinetically hindered in the gas phase, the presence of a discrete microhydration environment can drastically alter this landscape. Our M06-2X free energy calculations indicate that the cluster with two water molecules provides the lowest Gibbs free energy barrier among the investigated hydrated systems. However, benchmark electronic calculations show that the energetic differences between the mono-, bi-, and trihydrated clusters are small. HOMA index and QTAIM analyses confirm that the third water molecule induces an offset between aromaticity and intermolecular stabilization, providing a structural basis for the observed kinetic stabilization of the rare tautomer in a hydrated environment. In this work, we employ Hybrid-Meta DFT calculations to investigate the impact of sequential microhydration (0 to 3 water molecules) on the proton-transfer dynamics. Stable geometries for all stationary points (minima and transition states) were obtained through full optimization using the hybrid-meta M06-2X functional along with the def2-TZVP basis set. The nature of the stationary points was confirmed by harmonic frequency analysis. Furthermore, the normal modes associated with the imaginary frequencies were inspected to confirm that they correspond to the proton-transfer coordinate. Kinetic rate constants were calculated based on Transition State Theory (TST) at 298.15 K. Topological properties of the electronic density were obtained through QTAIM and NCI analyses.
In this work a DFT modeling of various routes of hydrogenation of a non-conjugated bicyclic diene—norbornadiene (NBD)—was carried out using the all-electron scalar-relativistic approximation. According to calculations, the determining role in selective hydrogenation of NBD to norbornene (NBE) belongs to the type of palladium surface and adsorption configuration (exo or endo) of NBD and NBE molecules. Pd(111) surface shows selectivity in NBD adsorption, as well as activity in selective hydrogenation of NBD to NBE. Gibbs activation energies of hydrogenation of NBD to NBE and NBE to NB on Pd(111) differ by 4.3 kcal/mol in favor of the former route, which determines the selectivity of NBD hydrogenation. Formation of byproduct nortricyclane (NTC) involves overcoming a large Gibbs activation energy (29.2 kcal/mol), explaining its experimental trace amounts. Despite the high selectivity of Pd(100) surface in NBD adsorption, it is almost inactive in its hydrogenation. Notably, Gibbs activation energy of hydrogenation route of NBD to NBE on Pd(100) is 5.2 kcal/mol higher than that of NBE to NB on Pd(100) and 9.2 kcal/mol higher than that of NBD to NBE on Pd(111). Despite the significant increase in the adsorption energies of NBD and NBE, that was calculated with Grimme’s D3 dispersion corrections, most of this difference is compensated when calculating activation energy. Main DFT calculations were carried out using the scalar-relativistic approximation. The PBE exchange–correlation functional and all-electron basis sets L2 for C and H atoms and L11 for Pd atoms were used. The Pd(111) and Pd(100) surfaces were modeled as 3-layered flat clusters Pd70 and Pd73, respectively. Geometry optimization for key intermediates and TSs using the PBE-D3(BJ) functional, def2-TZVP basis sets, and def2-ECP pseudopotentials was performed in ORCA 6.1.1 software. For the most energetically favorable adsorption configurations of NBD and NBE molecules, DFT-PBE and PBE-D3(BJ) calculations were performed under periodic boundary conditions in CP2K software.
Erectile dysfunction (ED) significantly affects male psychosocial health and has an increasing incidence. Although phosphodiesterase 5 (PDEi-5) inhibitors are the first-line therapy, the occurrence of visual side effects resulting from cross-inhibition of the PDE-6 isoform limits their adoption. In this context, the plant Veronica anagallis-aquatica L. emerges as a promising source of bioactive therapeutic compounds. This work investigated the inhibitory potential and selectivity of eight iridoid glycosides from this species against PDE-5 and PDE-6. The results identified catalposide as the most potent ligand, exhibiting an affinity energy of -8.6 kcal/mol against PDE-5, surpassing the reference drug Vardenafil (-8.3 kcal/mol) and showing high selectivity towards PDE-6. Trajectory analyses confirmed the robustness of the catalposide-PDE-5 complex, which exhibited smaller structural fluctuations than the commercial control. Despite initial predictions indicating low oral bioavailability, structural optimization through increased sp3 fraction proved to be a viable strategy for enhancing membrane permeability. In conclusion, the findings position catalposide as a promising prototype for the development of more selective and safe drugs for the treatment of ED. The two-dimensional structures of the ligands were constructed in Marvin JS and subjected to energy minimization using the semi-empirical PM7 method in MOPAC software. The preparation of macromolecules (addition of polar hydrogens and Gasteiger and Kollman charges) was performed in AutoDockTools. Virtual screening by molecular docking was performed in AutoDock Vina, with exhaustiveness set to 64. The stability of the protein-ligand complexes was evaluated through 500 ns molecular dynamics (MD) simulations using GROMACS 2020.4 software. The systems were solvated with the three-point water model (TIP3P) in a cubic box and described by the CHARMM36 force field. The ligand parameterization was generated via the SwissParam server. The simulations employed the LeapFrog integrator, temperature maintained constant at 310 K via V-rescale thermostat, and pressure coupling maintained at 1 bar using the Parrinello-Rahman method. For predictions of physicochemical properties, pharmacokinetic optimization, and ADMET profile analysis (including hERG toxicity), the predictive servers ADMETlab 3.0, optADMET, ADMET-AI, XenoSite, StopTox, and Pred-hERG were used. Three-dimensional structural complexity was evaluated from the calculation of the MCE-18 function.
Naringenin is a natural flavonoid compound with potential pharmaceutical use that is limited by its low aqueous solubility and bioavailability. In this work, we used an in silico drug delivery approach to screen natural deep eutectic solvents (NaDESs) that may improve solubility, membrane affinity, and predicted relative release of naringenin from 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes. Of all systems screened, betaine-based NaDESs were found to provide the best solubilization efficiency while choline chloride–caffeic acid provided the most stabilizing membrane affinity. Drug–membrane interactions characterized by free-energy, intermolecular interaction, and permeability calculations were shown to be dependent on the NaDES composition. In particular, a tunable relationship between hydrogen-bonding and van der Waals (vdW) interactions was shown to dictate encapsulation and Predicted relative release behavior allowing for rational computational selection of NaDESs to enhance liposomal delivery of poorly water-soluble drugs. Quantum chemical calculations were conducted based on density functional theory at M06/def2- TZVP level. Solubility, activity coefficients, intermolecular interactions and thermodynamics were predicted by COSMO-RS. Membrane partitioning, free-energy profiles, diffusion, permeability, and distribution in DMPC bilayers were assessed by COSMOmic.
Mitoxantrone (MTX) is an anticancer drug characterized by its hydrophobicity and low bioavailability, which can be increased by adding adjuvants to the formulation, such as surfactants (SFT). They can interact effectively with drugs, improve solubility and permeability, and stabilize them, thanks to unique properties such as amphiphilicity, adsorption, and micellization. This novel in silico study explores the intermolecular interactions between 128 surfactants and the chemotherapeutic anticancer agent “Mitoxantrone”, using molecular docking and the GIC approach. First, the MTX–SFT complexes were generated through ligand-ligand docking, showing various interactions (e.g., H-bond, π–π stacking, Pi-Alkyl). Next, to evaluate the effectiveness of these structural combinations in inhibiting Topoisomerase IIα (PDB ID: 1ZXM), a series of docking studies was performed to assess a variety of binding poses and ultimately determine the top-scoring complexes and the best binding poses. The docking results revealed that, among the 128 complexes generated, 70 complexes exhibited good Binding Energy (∆G) ranging from -34,727 to -48.116 kJ/mol. The ADMET evaluation was performed on the complexes with the highest affinity, identifying the top 33 complexes with favorable pharmacokinetic properties. Among the MTX-SFT complexes - that have top-scoring and exhibited greater inhibitory activity against topoisomerase IIα than other modified forms are MTX-Sodium Ricinoleate, MTX-Magnesium Ricinoleate, MTX-Glyceryl Laurate (Monolaurin), MTX-Sodium Lauroyl Sarcosinate, MTX-Sphingosine-1-Phosphate, MTX-Glyceryl Caprate, and MTX-Sorbitan Monolaurate (Span20). Additionally, the (GIC) approach demonstrated a strong relationship between molecular structure and interaction efficiency. The linear model yielded an AARD
