Structural Chemistry

In this research, density functional theory (DFT) was used with the B3LYP functional hybrid and the 6–311++G(d,p) basis set for the geometry optimization. First, the findings of the scanning for the potential energy surface (PES) for the vinyl chalcone (VC) have shown that the s-cis conformer was more stable than the s-trans conformer. The data also indicated that 1-butenyl chalcone (1-BC) is the most stable conformer and significantly improves the stability of unsubstituted chalcone (CA). VC was shown to be the least stable conformer. Second, the results were further supported by measuring the thermodynamic parameters thermal energy (TE), entropy (S), and heat capacity (Cv). TE, S, and Cv increased with the stability of conformer and decreased with the increased polarity of the solvent. Finally, the computed C = O stretching vibrations indicated that divinyl chalcone (DVC) causes the largest shift in the peak center of the C = O stretching vibrations of CA by a deviation 4.79 cm⁻¹ in the gas phase and 5.75 cm⁻¹ in n-hexane. The UV–Vis spectra for the studied conformers were analyzed by time-dependent density functional theory (TD-DFT) and the results displayed that the most planar conformers DVC and 1-BC have the highest values of maximum wavelength (λmax). The results shown that CA possesses the highest electronegativity (χ) while trans propenyl chalcone (E-PC) possesses the lowest electronegativity. The dipole moment (µ), polarizability (α), and first hyper polarizability (β) were seen to increase with the π-conjugation and solvent polarity. E-PC, 1-BC, and DVC constituted the highest magnitudes of µ, α, and β.

This work presents the study of the conformations of {[Choline][Chloride]:Phenol} ratio [1:2] and {[Choline][Chloride]:Glycolic acid} ratio [1:1] deep eutectic solvents in their isolated state and with the presence of water. The optimization of the geometries was carried out using density functional theory with the B3LYP functional and the 6–311(+ +)G(d,p) basis set. Through the study of the geometry optimization and the charge distribution, the most stable conformations of choline, choline chloride, the two aforementioned deep eutectic solvents and their cluster with water are detailed. The main hydrogen bonds are identified using the values of stabilizing energies between interacting orbitals. The results highlight the OH‧‧‧Cl type of hydrogen bonds as one of the key interactions. It is found that the chloride ion acts as a hydrogen bond acceptor while the choline ion acts primarily as a hydrogen bond donor. Glycolic acid and phenol can play both roles. The molecule of water is able to form various hydrogen bonds. The strongest hydrogen bonds are observed between the chloride ion and a hydroxyl group. Finally, an increasing total number of hydrogen bonds in a system decreases the strength of the overall interactions.

In the present paper, we report crystal structures of four types ([A(1)H][A(2)H]Y, [A(1)H]3[A(2)H]Y2, A(1)H[A(2)H···A(2)]Y, and A(1)H[A(1)H···A(2)]Y) of mixed salts containing the sulfate anion (Y = SO4²⁻) and amino acids A, i.e., sarcosine (Sar), dimethylglycine (DMG), betaine (Bet), β-alanine (β-Ala), and l-proline (l-Pro): (β-AlaH)(DMGH)SO4·2H2O (I), (β-AlaH)(BetH)SO4 (II), (β-AlaH)(l-ProH)SO4 (III), (BetH)(l-ProH)SO4 (IV), (SarH)3(l-ProH)(SO4)2 (V), (β-AlaH)(l-ProH···l-Pro)SO4 (VI), and (β-AlaH)(β-AlaH···DMG)SO4 (VII). The O···O distances in dimeric cations (l-ProH···l-Pro) and (β-AlaH···DMG) are 2.450(3) and 2.5295(12) Å in (VI) and (VII), respectively. Crystal structure determinations of (β-AlaH)(BetH)SO4 (II) at 100 K (P21/n), 200 K (Pnma), 250 K (Pnma), and room temperature (Pnma) revealed a structural phase transition in the interval between 100 and 200 K.

Various undesirable side effects are frequently associated with isomers of chiral clinical agents. The separation of chiral medicines remains a challenging issue in the medicines research. In this work, we employed cyclic decapeptide as the host molecule and the M06-2X theoretical computational method for chiral recognition of four clinical candidate guests and their isomers, including bucillamine, molnupiravir, azvudine, and VV116, which are relevant for the treatment of COVID-19. The obtained results indicated that bucillamine and molnupiravir and their respective isomers may be distinguished by cyclic decapeptide and that some of the isomers of Azvudine and VV116 may be discriminated by cyclic decapeptide. The inclusion conformation, deformation analysis, and electrostatic potential analysis also visualized the binding modes and binding sites between cyclic peptides and medicine candidates. A series of weak interaction analyses suggest that hydrogen bonding and dispersion interactions may be the primary factors for the recognition and separation of the clinical candidates by cyclic decapeptides. Visualized analyses of noncovalent interaction, hydrogen bond interaction, and NBO, AIM topological demonstrated that the difference of dispersion interaction is not obvious between the complexes, while the type and number of hydrogen bonds are very different, hinting that hydrogen bonds might be crucial for the differentiation of molnupiravir and its isomers. These findings might provide a theoretical reference for the identification and separation of chiral compounds in host–guest interaction.

The Nobel laureate Paul Berg initiated genetic manipulation and pioneered genetic engineering. He was also one of the initiators of setting up guidelines for carrying out recombinant DNA experiments. He was an innovative scientist and cared for the impact of science on society.

A theoretical investigation of the metal chelation ability of piceatannol ligand (PIC) with Ti(IV) and Zr(IV) metal ions is undertaken in this work utilizing DFT/B3LYP-GD3/6-31 + G(d,p) level theory in gas and DMSO. PIC is a naturally occurring polyphenolic stilbene having anticancer properties. Interaction of the deprotonated form of PIC with metal ions forms [TiL 2 ] and [ZrL 2 ] complexes. The stability of the complexes is evaluated using geometrical parameters, binding energy, and thermodynamic properties like ∆H and ∆G. The observed results indicate the higher stability of [TiL 2 ] complexes. Topol-ogy, NCI, and IRI analyses were used to explore the metal-ligand interactions in formed complexes. This establishes the metal-oxygen bonds in both complexes as an ionic bonding domain on the boundary of the intermediate bonding regime, which comprises dative bonding with a weak covalent character. The interaction of PIC with metal ions is less favourable in implicit DMSO. This is due to the presence of a solvent, which may compete with the ligand for interaction with the ion, reducing complex stability. The ligand and complexes are examined against protein kinase B using deep learning-based GNINA 1.0 software, and the results show a higher negative binding affinity of the [TiL 2 ] complex in comparison with others. These complexes outperform PIC as an anti-cancer drug candidate by inhibiting Akt kinase.

Nipah virus (NiV) is a high-lethality RNA virus from the family of Paramyxoviridae and genus Henipavirus, classified under Biosafety Level-4 (BSL-4) pathogen due to the severity of pathogenicity and lack of medications and vaccines. Direct contacts or the body fluids of infected animals are the major factor of transmission of NiV. As it is not an airborne infection, the transmission rate is relatively low. Still, mutations of the NiV in the animal reservoir over the years, followed by zoonotic transfer, can make the deadliness of the virus manifold in upcoming years. Therefore, there is no denial of the possibility of a pandemic after COVID-19 considering the severe pathogenicity of NiV, and that is why we need to be prepared with possible drugs in upcoming days. Considering the time constraints, computational aided drug design (CADD) is an efficient way to study the virus and perform the drug design and test the HITs to lead experimentally. Therefore, this review focuses primarily on NiV target proteins (covering NiV and human), experimentally tested repurposed drug details, and latest computational studies on potential lead molecules, which can be explored as potential drug candidates. Computationally identified drug candidates, including their chemical structures, docking scores, amino acid level interaction with corresponding protein, and the platform used for the studies, are thoroughly discussed. The review will offer a one-stop study to access what had been performed and what can be performed in the CADD of NiV.

Polymeric materials as drug carriers were applied to enhance the solubility of Silymarin. The structures (drug and drug-ethylene glycol derivatives compounds) were modeled in the gas phase by quantum mechanical calculations. Afterward, the optimized Silymarin-ethylene glycol derivatives were modeled in an aqueous environment, and solvation free energies and association free energies were calculated by Monte Carlo simulation and perturbation method. Diethylene glycol and diethylene glycol-dilactic acid could be associated with Silymarin in an aqueous solution. Application of ethylene glycol derivatives enhances the solvation free energy of Silymarin in aqueous media.

Due to less sensitivity of graphene towards the cisplatin (CPT), the graphene is modified by doping systematically boron atoms (B/Gra), nitrogen atoms (N/Gra), and hexagonal boron nitride (BN/Gra) to form hetero-quantum dots (QDs). In our DFT investigations, the CPT drug adsorbs on the surface of modified QDs within favorable range of adsorption energy. Among them, B/Gra QD shows high adsorption behavior with CPT at about −1.44 eV and −0.6 eV energies in gas and water solvent phases. On the other hand, BN/Gra and N/Gra hetero-QDs interact with CPT at about −0.88 eV and −1.03 eV adsorption energies respectively. During interaction of CPT with B/Gra, CPT loses 0.215 e and 0.129 e charge to the B/Gra in gas and solvent phases. About 26.4% and 14% reductions of E g have been occurred after the interaction of CPT with B/ Gra. Furthermore quantum molecular descriptors also suggest the high sensitivity of the B/Gra QDs with the CPT. Therefore, B/Gra QD can be used as drug carrier for CPT.

Walter Kohn (1923−2016) was an Austrian-born American physicist who received half of the Nobel Prize in Chemistry in 1998 “for his development of the density-functional theory.” He was a refugee from Nazism. He learned from great scientists and contributed to many areas of physics, chemistry and materials science using theory and computation.

Four mechanisms have been proposed in the literature to explain beryllium toxicity; they can be divided in two groups of two mechanisms: (i) replacement type: models 1 and 2; (ii) addition type: models 3 and 4. At this moment is not possible to select the best model not even to establish if one of these models will be the ultimate mechanism of beryllium toxicity. However, it is important to know the still open discussion about something so important associated with one of the simplest elements of the periodic table.

Vacancies in graphene are places with altered chemical reactivity and the possibility of adjusting the properties of graphene by defective engineering. Understanding the chemical reactivity of such defects is essential for the successful implementation of carbon materials in advanced technologies such as adsorption and elimination of compounds. To improve the agricultural potential of saline soils, the elimination of the responsible cations including Na⁺, K⁺, Mg²⁺, and Ca²⁺ with nitrogen-functionalized porous graphene (NPG) was considered by density functional theory (DFT) calculations. The adsorption energy as an important parameter of trapping has been calculated. The NBO results show strong interactions between lone pair (LP) of N with LP* of cations which reveals that the charge transfer plays an important role in the formation of the complex M/NPG. Our results demonstrate that NPG would be a potential candidate for salinity stress management with alkali and alkaline earth cation elimination.

Tautomerism is one of the most important phenomena to consider when designing biologically active molecules. In thiswork, we use NMR spectroscopy, IR, and X-ray analysis as well as quantum-chemical calculations in the gas phase and in asolvent to study tautomerism of 1- (2-, 3- and 4-pyridinecarbonyl)-4-substituted thiosemicarbazide derivatives. The tautomercontaining both carbonyl and thione groups turned out to be the most stable. The results of the calculations are consistentwith the experimental data obtained from NMR and IR spectroscopy and with the crystalline forms from the X-ray studies.The obtained results broaden the knowledge in the field of structural studies of the thiosemicarbazide scaffold, which willtranslate into an understanding of the interactions of compounds with a potential molecular target.

Crystal and electronic structures of a newly synthesized thiazolium pentaiodide, C3H4NS(I5), were examined in detail. The title pentaiodide crystallizes in the monoclinic space group P21/m with the unit cell volume of 1289.27(6) ų. Its crystal structure features branched pentaiodide chains composed of alternating I3⁻ and I2 building units, whereas the chains are further linked into a 3D array by thiazolium cations with the help of (N)H⋅⋅⋅I and S⋅⋅⋅I bonds. The electronic structure and bonding assessed by DFT calculations show that covalent interactions within the I2 and I3⁻ units are supplemented by non-covalent (N)H⋅⋅⋅I and S⋅⋅⋅I interactions, which were revealed by the electron localization function and reduced density gradient analyses.

By analogy to the understanding of the energetics of amides, the current study discusses the stabilization/destabilization energy of α-diketones, dienes and derived radical ions.

Many sciences are described by two conceptually different but complementary theories, one visual and insightful the other better suited to computation. Chemistry has a powerful computational theory in quantum mechanics, but its visual and insightful theory of valence has never been properly developed. The rigorous theory of valence described here takes the atom as its fundamental particle. As the theory has no knowledge of the atom’s internal structure, the valence is not associated with the electron, hence it is free to adopt fractional values. Each atom is characterized by two experimental properties: its valence determined from the compositions of observed compounds, and its size determined from its observed coordination numbers. These two properties are able to describe a surprising amount of chemistry. The amount of valence an atom typically uses to form a bond determines both the conditions under which bonds can be formed and their resulting properties. A valence definition of electronegativity removes the need to distinguish between ionic and covalent bonds by defining the more nuanced concept of bond polarization, clearing up much of the confusion found in popular bonding models. The theory is compatible with the physical picture provided by quantum mechanics but not with the physically unrealistic ionic model. It can be used for analyzing, modeling, and teaching of chemical structure and reactivity, but having no knowledge of the internal structure of the atom it cannot be used to calculate energies or any of the properties that depend on the energy; for that quantum mechanics must be used.

In response to the malaria parasite’s resistance towards quinoline-based antimalarial drugs, we have employed quinoline-containing compounds in combination with dihydropyrimidinone (DHPM) analogues as resistance reversal agents (RAs) and investigated their antimalarial activities based on DHPM’s resistance reversal abilities. The present study employed click chemistry to link DHPM and quinoline compounds which offered several synthetic advantages over the previously used amide coupling for the same hybrids. Among the synthesised compounds, 4 hybrids with the 7-chloroquinoline moiety showed antimalarial activity below 1 µM while compounds with the mefloquine moiety showed lower antimalarial activity than chloroquine (CQ) and the 7-chloroquinoline hybrids. Among the tested hybrids for the IC50 determination, four compounds displayed good antimalarial activity with increased sensitivity against the CQ-resistant K1 strain between 421 and 567 nM and showed higher activity between 138 and 245 nM against the NF54 CQ-sensitive strain, while three compounds have IC50 values greater than 5 µM. Additionally, in silico molecular docking and molecular dynamics studies were conducted to investigate the binding affinities of all the synthesised compounds as glutathione reductase protein competitive inhibitors. Further optimisation of the compound with the highest binding affinity generated 16 compounds with higher binding affinities than the flavine adenine dinucleotide (FAD) cofactor.

Density functional theory (DFT) calculations were carried out on ML2Cl2 (M = Co, Ni) and M’LCl2 (M’= Zn, Cd) and L=(BDQ) quinolino[3,2-b]benzodiazepine or L = (BDO) = quinolino[3,2-b]benzoxazepine) transition metal complexes. The geometry optimizations and frequency calculations of the aforementioned complexes were performed at the Becke, 3-parameter, Lee–Yang–Parr/triple zeta polarization (B3LYP/TZP) level, followed by the partitioning of the interaction energies using the energy decomposition analysis scheme (EDA) to assess the interaction strength in function of L ligand and the nature of the metal. Indeed, the total bonding energies are more significant for Zn(II) cation in the presence of (QBD) ligand than those of the Cd(II) one and (QBO). The findings show that the electrostatic interaction energy is the most important contributing by two third into the total interaction energy of each of the complex systems. Calculations and analyses were performed by means of the natural bond orbital analyses (NBO) giving rise to significant natural population of the M(II) cations. As concerns of the structures corresponding to odd electron counts, the unpaired electrons are chiefly localized on the metal center with regard to the spin density values. UV–Vis spectra are mainly π→π* electronic transitions corresponding to intra-ligand charge transfers (ILCT) but showed weak influence of the introduction of the MCl2 metallic fragment.

Reaching back to his discontinued research done some 50 years ago, a retired chemist proposes novel synthetic routes to 3′-thiocytidylates and their polymers. The driving force of these reactions is based on the superior nucleophilicity of the thiophosphate anion coupled with charge interactions in facilitating displacement reactions on anhydrocytidine moieties. The products of these reactions could be of biochemical and pharmacological interest. If the polymerization reaction would indeed take place in water as suggested, it might fill a gap in prebiotic/origin of life chemistry.

Boronic acids and their conjugate esters have been employed in a variety of biomedical applications. This work reports structural, bonding, and thermochemical calculations for the boronic acids, RB(OH)2 (R = H, methyl, phenyl, and ortho-methyl-phenyl) and the corresponding ethylene glycol diesters, RB(−OCH2CH2O−), in the presence of explicit NH3 and/or H2O molecules. Calculations were performed in vacuo and in polarizable continuum model (PCM) aqueous media using density functional theory (DFT) and second-order Moller-Plesset perturbation theory (MP2) with the Dunning-Woon aug-cc-pVTZ basis set. These results quantify the relative stability of N→B dative-bonded, water-inserted Owater→B (Ow→B) dative-bonded, Zwitterionic, and hydrogen-bonded conformers on the model RB(OH)2⋅NH3⋅H2O and RB(−OCH2CH2O−)⋅NH3⋅H2O potential energy surfaces (PESs). In the PCM aqueous media model, conformers containing an H3N→B dative bond and a water molecule bridging the NH3 and acid/ester moieties were found consistently to be lower in energy than arrangements with either a H3N⋯H(H)Ow→B linkage or Zwitterionic forms, [H4N]⁺[HOw−BR(OH)2]⁻ or [H4N]⁺[HOw−BR(−OCH2CH2O−)]⁻. For the acids, however, conformers with a H3N⋯HOwH moiety hydrogen bonded to the boronate hydroxyl group(s) proved to be lowest in energy.

Structural chemistry provides the foundation for progress in organic and inorganic chemistry with far-reaching consequences in medicine and in materials science and technology. New tools and concepts appear shaping together the progress in structural chemistry.

New organic dyes (H1-H6) for their promising applications as dye sensitized solar cell (DSSCs) were theoretically designed from 6,6′-di(thiophen-2-yl)-4,4′-bipyrimidine (TB) moiety in acceptor (A), π-spacer, and donor (D) type architecture to create A-π-D-π-D-π-A framework. After their benchmarking study against various exchange correlation (XC) and long-range corrected (LC) functional, the CAM-B3LYP produced accurate results so as selected for further density functional theory (DFT) and time dependent DFT (TD-DFT) studies. The frontier molecular orbitals (FMOs) were analyzed for their electron transfer properties, and their energies of the highest occupied molecular orbital (EHOMO) and the lowest unoccupied molecular orbital (ELUMO) were used to assess various electronic properties. Their energy differences (EH-L) ranged between 1.69 and 2.03 eV indicating their good responsiveness to electron injection (Ginj) being the values greater than 0.2 eV. The maximum absorbance of the dyes was reported around the 388–406 nm while their starting material (TB) had this value to be 371 nm. This redshift was significant with an intensification of electron-withdrawing groups on the dye structures. The dyes were evaluated for their device related parameters like their light harvesting efficiency, open circuit voltage, exciton binding energies, and exciton life times which were found in their promising values. The dyes were analyzed for their linear (α), first (βtotal), and second (γtotal) order nonlinear responses and were found to have significantly higher responses, not only against their starting materials but also those reported in literature for standard molecules (urea and p-nitric acid). Among the dyes under study, dye H4 exhibits the highest molecular polarizability (α) and hyperpolarizability (β and γ) values thanks to two CN substituted units on each ends. These dyes are most likely to have possible optical and photonic uses. Also, according to the results of the current theoretical research, all of these dyes may function as effective photosensitizer for their DSSC application.

Density functional theory is applied to account the ligand effect on modification in the redox potential of coordination of three NN bidentate ligands (bpy/phen) to the metal ion (Fe2+/3+/Co2+/3+). Also, the role of the ligand framework for the stabilization of [M(bpy/phen)3]2+/3+ species is discussed in detail. In this work, we have found that the M²⁺ ions are more stabilized with the bpy ligands while the M³⁺ ions are more stable with the phen ligands. The electronic structure and geometrical study disclosed the electronic configurations of the metal ions in both the possible spin states of a species. Furthermore, the HOMO–LUMO analysis demonstrates that the M³⁺ ion coordinated species have more energy gap as compared to the M²⁺ ion coordinated species. Among all the species, HOMO–LUMO energy gap has been found highest (4.62 eV) in the [Fe(bpy)3]³⁺ whereas lowest (3.28 eV) in the [Co(phen)3]²⁺ species. Additionally, we have also found that the bpy coordinated species have relatively higher redox potential value as compared to phen ligated species. Here we have noticed a close relationship between the redox potential and the optimized structural parameters of the studied species. Also, all the computed structural parameters of the studied species are in good agreement with the experimental data.

The four-membered ruthenium(II) organometallics Ru(η²-RL)(PPh3)2(CO)(Cl) (1) where η²-RL = C6H2O-2-CHNHC6H4R(p)-3-Me-5 and R = CH3 reacts with 2-(2-hydroxyphenyl)benzothiazole (Hhpbt) and 2-(2-hydroxyphenyl)benzoxazole (Hhpbo) in refluxing ethanol to afford Ru(PPh3)2(CO)(hpbt)Cl (2) and Ru(PPh3)2(CO)(hpbo)Cl (3) respectively in excellent yield. In the course of these reactions, the Ru − C(aryl) bond in 1 is cleaved, and the RL ligand is no longer coordinated with the metal center in the products. The spectral (UV–vis, IR, ¹H NMR) and electrochemical data of the complexes are reported. The identity of complex 2 has been established by single-crystal X-ray structure determination. The electronic structure and the absorption spectra of the complexes are scrutinized by DFT and TD-DFT analyses. The complexes were also tested for their ability to exhibit DNA-binding activity.

Cathepsin K and S are two isoforms of cysteine protease with diverse biological functions in the aspect of osteoporosis and autoimmune diseases. Accordingly, the homologous sequence and similar binding site features among CTSK/S may lead to unselective inhibition and side effects. To address such issue, various computational strategies were applied in the current study to explore the selectivity mechanism of CTSK/S inhibitors, including sequence alignment, molecular docking, MD simulations, MM/GBSA energy calculation, and so on. Our findings highlight the notable effects of CTSK residues Glu59 and Tyr67, as well as CTSS residue Asn67, on inhibition selectivity. Overall, this study provides an informative guideline for the rational design of CTSK/S selective inhibitors.

The Nobel Assembly at Karolinska Institutet awarded the 2022 Nobel Prize in Physiology or Medicine to a Swedish geneticist, Svante Pääbo, for his discoveries concerning the genomes of extinct hominins and human evolution, for the sequencing of the genome of the Neanderthal, the discovery of a previously unknown hominin, Denisova, and the establishment of a new scientific discipline, paleogenomics.

The exploration on the redox properties of sodiated quinone molecules as organic cathode material in sodium-ion batteries has been comprehensively studied. As the electrochemical performance of the cathode material is known to depend on the intrinsic molecular properties such as conformations, the present work focuses on the redox properties of sodiated 1,4-benzoquinone (1,4-BQ) conformers employing the density functional theory. Such investigation on the sodiated structures might provide insight on the discharge state of the puckered conformers. The 38 conformers of 1,4-BQ (2 chairs, 6 boats, 6 skew-boats, 12 half-chairs, 12 envelopes) constructed from the torsion angles given by Berces et al. are optimized at B3LYP/6–311 + G(d,p) level of theory and their structural propensities during the reduction process are explored. The influence of puckering over the charge distribution of neutral, anionic and sodiated structures is analysed using the natural bond orbital method. The electrochemical performance of Na incorporated conformers is explored through the calculation of electron affinity, change in Gibbs free energies and redox potentials. The conductor-like polarizable continuum model (C-PCM) is used to include the solvation effects of the electrolyte such as ethylene carbonate. A good correlation between the conformers with more negative lowest unoccupied molecular orbital (LUMO) energies and their redox potentials and electron affinity is observed. Noticeable variation in the frontier energies and redox potentials of the sodiated quinone conformers emphasize the significance of intrinsic molecular level properties to play a major role in the overall electrochemical performance of quinone-like electrode materials in sodium-ion batteries.

X-ray molecular and supramolecular structure were analyzed for N-t-Bu-N′-(triflyl)acetamidine t-BuNHC(Me) = NTf 1 and compared to that of N-bromobicycloheptanyl-N′-(triflyl)acetamidine 2. Self-associates of amidines 1, 2 bound by NH···O = S bonds form lamellar structure with the layers linked by CH···O = S short contacts. DFT calculations were performed for the conformational isomers, tautomers RNHC(Me) = NTf (a) or RN = C(Me)NHTf (b), the solvate H-complexes, and self-associates. The calculations showed good agreement of the experimental and theoretical geometry for the associates of 1 in polar medium. The IR spectra of 1 were taken in different states at variable temperature and concentration and its conformational composition was analyzed using the results of calculations. The free energy barriers of 20–25 kcal/mol were calculated for the syn-anti rotation about the C–N bond. The barriers of the 1a ⇌ 1b tautomerization in the E-isomer and its complexes with dioxane and MeCN (37–45 kcal/mol) are too high to occur under usual conditions, whereas in the complex with hexafluoroisopropanol, it is much lower (< 17 kcal/mol) rendering the process kinetically more feasible. The C = N and C–N bonds are equalized or even invert due to conjugation in the amidine fragment, which is different in the conformational isomers, in dimers, and in different media.

Some particularities in the bonding of simple sulfenic acids and their sulfoxide isomers are explored using accurate theoretical methods. Some unexpected results are described using thermochemical results on diverse nitrogen- and/or oxygen-containing functionalities such as amino, nitro, nitroso, and nitrite derivatives.

In this work, we have investigated the complex formation capability of gemcitabine drug with host cucurbit[n]urils, Q[n] (n = 6, 7, and 8) using density functional theory (DFT). The DFT studies demonstrate that the most stable configuration is a fully encapsulated complex. In the encapsulated gemcitabine@Q[6] and gemcitabine@Q[7] complexes, the gemcitabine amino -NH2 and the alcoholic groups bond with the carbonyl units of Q[n]. The addition of sodium ions leads to the partial exclusion of the gemcitabine molecule and the sodium atoms lie close to the carbonyl portal of Q[7]. Thermodynamic parameters computed for the complexation process exhibit high negative Gibbs free energy change, implying that the encapsulation process is spontaneous and is an enthalpy-driven process. Frontier molecular orbitals are located mainly on the gemcitabine uracil ring, before and after encapsulation, indicating that the encapsulation occurs by pure physical adsorption. Quantitative molecular electrostatic potentials demonstrate a shift in electron density during the complex formation and are more pronounced in gemcitabine@Q[7]. Atoms-in-molecule (AIM) topological analysis illustrate that these complexes are stabilized by various non-covalent interactions including hydrogen bonding (HBs) and C···F interactions. The reduced density gradient (RDG) graph exhibits the presence of strong HBs and weak van der Waals interactions and the presence of steric repulsion. The isosurface non-covalent interactions (NCI) diagram shows predominant steric interaction in the gemcitabine@Q[6] complex. The NCI isosurface for gemcitabine encapsulated complexes with Q[7] and Q[8] host displays that the green patches are uniformly distributed in all directions. Finally, EDA results demonstrate Pauling’s repulsive energy is predominant in gemcitabine@Q[6] complex, while the orbital and dispersion energies stabilize the gemcitabine@Q[7] complex.

Nanocarriers allow the connection between biomolecules and other structures to enhance the treatment efficacy, through the biomolecule’s properties to an existing drug, or to allow a better and specific delivery. Apigenin and orientin are biomolecules with excellent therapeutic properties that are proposed in the fight against COVID-19. Besides that, graphene oxide is a nanomaterial that exhibits antiviral activity and is used as a nanocarrier of several drugs. We evaluated in this work, through molecular docking, the binding affinity between these structures to the receptor-binding domain of spike protein of two coronavirus variants, Delta and Omicron. The results indicate that all the structures exhibit affinity with the two protein targets, with binding affinity values of −11.88 to −6.65 kcal/mol for the Delta variant and values of −9.58 to −13.20 kcal/mol for the Omicron variant, which is a successful value as found in the literature as a potential inhibitor of SARS-CoV-2 infection. Also, through first-principles calculations based on Density Functional Theory, the interaction of graphene oxide with the biomolecules apigenin and orientin occurred. The results exhibit weak binding energy, which indicates that physical adsorption occurs, with better results when the biomolecule is set in parallel to the nanomaterial due to attractive π-π staking. These results are conducive to the development of a nanocarrier.

COVID-19 which is caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has been declared pandemic in 2019. Though there is development of vaccines but there is an emergence requirement of drugs against SARS-CoV-2. Antiviral peptides can be rationally created and improved based on the known structures of viral proteins and their biological targets. In the given study, small peptide inhibitors with three amino acids are designed and docked against SARS-CoV-2 coronavirus using molecular docking approach. All the designed peptides bind at the active site but the highest binding affinity was observed for HisGluAsp. Molecular dynamics was performed to validate the stability and interactions of compound. The molecule has followed the druglikeness properties and with highest probability of being absorbed by the gastrointestinal tract. The results of the current investigation point to the possibility that the identified small peptides may prevent SARS-CoV-2 infection, although additional wet-lab tests are still required to confirm these results.

In this work, seven organic dyes were designed (M2–M7) to have the D-π1-Ai-π2-A structure from the reference dye M1, which has the D-π1-π2-A structure. By inserting different auxiliary acceptors Ai (i = 1–7) between the π1 and π2 onto the reference dye M1, we obtained the designed dyes to study their photovoltaic properties for use in DSSC devices. The geometrical structures, absorption spectrum properties, nonlinear optical properties (NLOs), energy levels, frontier molecular orbitals, and some photovoltaic parameters were theoretically investigated using density function theory (DFT) and time-dependent DFT (TD-DFT) methods, with the aim of improving the DSSC performance of the designed dyes. The theoretical results reveal that the designed dyes would be used as potential sensitizers in DSSCs due to their very small energy gaps, broad absorption spectra, higher NLO properties, lower reorganization energy (λtot), lower regeneration driving force (ΔGreg), longer excited lifetime (τ), higher vertical dipole moment (µnormal), reasonable electron injection driving force (∆Ginj), and equally reasonable light-harvesting efficiency (LHE) compared to the reference dye M1. Furthermore, the designed dyes (M2–M8) have better charge transferability, the highest stabilization energy, and the highest ability of electron-donating and electron-accepting, resulting in a high short-circuit current and better power conversion energy (PCE) compared to reference dye M1. These results show that the introduction of different auxiliary acceptors Ai can most effectively improve the photovoltaic performance of our system.

Thioredoxin reductase (TrxR) plays an important role in the reduction of thioredoxin (Trx), which is found to be involved in the upregulation of a diversity of tumors, including those related to chemo-resistant tumors. In recent years, thioredoxin reductase (TrxR) has been identified as a very important regulator of tumor development, and therefore, targeting TrxR is a promising strategy for cancer therapy. The 3/2D-QSAR models were established in this study, such as HQSAR, and the study was based on CoMFA and CoMSIA analyses. The established optimal 2D-QSAR (HQSAR) model gave Q² = 0.756, R² = 0.959, and = 0.90, the established optimal CoMFA model gave Q² = 0.671, R² = 0.925, and = 0.853, and the CoMSIA/SEA model gave Q² = 0.627, R² = 0.962, and = 0.927. The predictive ability of the three proposed models was successfully evaluated using the criteria validation method of Golbraikh et al. [1] and Kunal Roy [2]. The visualization of the CoMFA contour map, the CoMSIA/SEA contour map, the HQSAR contribution map analysis, and the molecular docking results revealed that the R3 surrogate is important in enhancing or decreasing anti-cancer biological activity. Molecular dynamics (MD) simulation results revealed that both inhibitors remained stable in the active sites of the 3EAO protein for 100 ns. To propose new molecules based on a change in the R3 substituent, the three proposed models predicted the TrxR inhibitory activities of the four proposed new molecules, which were then evaluated using Lipinski’s rule, synthetic accessibility, and ADMET properties of each molecule. The obtained results have revealed that the compound C3 will be of great value as a new anti-cancer drug candidate.

Nano-kaolin-SO3H was prepared and used to synthesis of N-nitrosamines. The products were characterized by their spectral (IR and ¹H NMR) data. N-nitrosamines can exist in two mesomeric forms but the reaction is quite regioselective and only one of mesomers is formed as a main product which can exist in two E and Z stereoisomers. In this paper, we have studied the mesomeric effect of N-nitrosamines which explained the diastereotopic nature of corresponding protons in symmetric N-nitrosamines and formation of two isomers in asymmetric N-nitrosamines.

Here, we present the preparation and characterization of two novel picrate salts. The 2,2′-bis(pyridinium)ketone picrate, DPK-PA (1), crystallizes in the triclinic system and centrosymmetric space group P 1¯, with unit cell parameters a = 9.378(17) Å, b = 9.790(15) Å, c = 10.141(16) Å, α = 99.63(7)°, β = 99.09(8)°, and γ = 102.55(8)°, while the 4,4′-bis(tert-butyl)-2-pyridine-2-pyridinium picrate, BBBPY-PA (2), crystallizes in the non-centrosymmetric P212121 space group, orthorhombic unit cell parameters a = 6.3902(6) Å, b = 23.416(3) Å, and c = 16.7320(18) Å. Both crystal structures present an ion-pair in the asymmetric unit, one picrate anion, and one bipyridine derivative. In the DPK-PA (1) structure, the molecule of DPK presents one intramolecular N1-H ⋯ N H-bond that contributes to stabilizing the planar conformation of DPK. The absence of intramolecular H-bonding in the BBBPY-PA (2) can be explained by the steric hindrance of the tert-butyl group. For DPK-PA (1) and BBBPY-PA (2), the crystal packing is stabilized N–H ⋯ O strong hydrogen bonding interactions, which could be identified by the Hirshfeld surface analysis and fingerprint plots. The compounds were also studied by UV–Vis and infrared analyses, which may support the statement of the formation of new material. Finally, as an attempt to obtain a molecular system to act as a chemical sensor, we studied the fluorescence of both compounds, in solution and in solid state; however, no fluorescence was observed.

Single crystals of 8-hydroxy-5-nitroquinolinium p-toluene sulfonate (HNT) were grown by the slow evaporation solution growth technique. The structure was elucidated by single-crystal X-ray diffraction analysis, and the crystal belongs to the monoclinic system with the space group C2/c. The crystallinity of HNT was studied by powder X-ray diffraction analysis. The presence of functional groups was determined by FT-IR spectral analysis. The band gap energy is estimated by the application of the Kubelka–Munk algorithm. The charge transfer characteristic of the compound was studied by frontier molecular orbital (FMO) analysis. The first-order hyperpolarizability of the HNT molecule was found to be 285.45 × 10⁻³⁰ esu, which is ~ 750 times higher compared to the reference urea molecule. Investigation of the intermolecular interactions and crystal studies packing via Hirshfeld surface analysis, based on single-crystal XRD, reveals that the close contacts are associated with molecular interactions. Fingerprint plots of the Hirshfeld surfaces were used to locate and analyze the percentage of hydrogen-bonding interactions. The Mulliken charge of the present molecule was theoretically analyzed. The Kurtz-Perry powder technique has been used to estimate the second harmonic generation. Observed small SHG and large hyperpolarizability are rationalized.

High levels of volatile or semivolatile organic chemicals are released yearly into the atmosphere. Oxidation of anthropogenic pollutants via the reaction of hydroxyl radicals is one of the most effective means of their removal from the atmosphere. This computational study examined the mechanism of removal of aldehyde from the atmosphere via hydrogen abstraction by highly reactive hydroxide radical. The chemistry of the carbonyl bond of the aldehyde changed significantly from reactants to products. The minimum energy path (MEP) analysis with the kinetic study shows that the reaction for the abstraction of hydrogen from the aldehyde is both thermodynamically and kinetically favourable. The hydrogen abstraction of the aromatic aldehydes especially without methyl substituents is more kinetically favourable compared to the other aldehyde in the order of aromatic (without methyl or meta methyl) > alkane (short chain) > diene > long-chain aldehyde compounds. The entropy favours both the kinetic and thermodynamic of the aliphatic over the aromatic aldehyde compounds. The natural energy decomposition analysis (NEDA) of the interaction energy of the aldehyde and hydroxide radical also shows that a more favourable interaction of the reaction species is obtained for those that are thermodynamically favourable especially the interaction of the two components of reactants compared to those of the products. The molecular electrostatic potential (MESP) analysis also shows that the reaction sites in the reactants are more prone to reaction compared to what was observed in the products and transition state when considering the value of Vmin.

The mechanisms for the deamination reactions of 6-thioguanine (6-TG) with H2O, OH−, and OH−/H2O and for protonated 6-thioguanine (6-TGH+) with H2O have been studied by theoretical calculations. Six pathways, paths A–F, have been explored and relative energies, enthalpies, and Gibbs energies were calculated for each reaction path. Compared with the deamination reaction of 6-TG with H2O or 6-TGH+ with H2O, the deamination reaction of 6-TG with OH− shows a lower overall Gibbs energy of activation, indicating that the 6-TG deamination reaction is favorably to occur for the deprotonated form 6-TG− with H2O. With the assistance of an additional water molecule, the deamination reaction of 6-TG with OH−/H2O (path F) is found to be the most feasible pathway in gas phase and also in aqueous solution. The overall Gibbs energy of activation for path F in gas phase and in aqueous solution is 169.8 and 140.6 kJ mol−1 (SMD model), respectively, at the B3LYP/6–311++G(d,p) level of theory.

The crystal structures of uranyl fluoride complexes with alkali metal cations and ammonium, with protonated cations of organic bases, with divalent transition metal cations, and with mixed monovalent and divalent transition metal cations studied by the single-crystal X-ray diffraction method have been systematized and discussed. The crystal chemical features of the structures of the uranyl fluoride complexes were determined: the coordination polyhedron of the hexavalent uranium atom in the structures of the uranyl fluoride complexes has a pentagonal-bipyramidal structure; the oxygen atoms of the uranyl group are located on the vertical axis of the bipyramid, perpendicular to the equatorial plane in which five atoms of the coordinated ligands are located. With the exception of UO2F2 (uranium center CN 6), a pentagonal-bipyramidal configuration of the central atom polyhedron is realized in all the studied structures of the fluoride complexes of uranyl. Based on the performed studies on the structural chemistry of uranyl fluoride complexes, the regularity in the formation of this class of compounds was established. The dependence of the frequency of the asymmetric stretching vibration of the uranyl ion on the structure of the complex anion and on the formation of hydrogen bonds in the structures of the investigated uranyl fluoride complexes has been established.

In this article, a novel energetic cocrystal composed of CL-20 and bicyclo-HMX was designed. The crystal models of pure components (CL-20, and bicyclo-HMX) and CL-20/bicyclo-HMX energetic cocrystal models with different molecular ratios were established. Molecular dynamic (MD) method was adopted to optimize the cocrystal structure and predict its properties, including sensitivity, stability, mechanical properties, and energetic performance. Results show that the trigger bond (N-NO2 bond) energy in CL-20/bicyclo-HMX energetic cocrystal model is increased, meaning that the trigger bond strength is enhanced and the cocrystal explosive should have lower mechanical sensitivity than pure CL-20. The CL-20/bicyclo-HMX cocrystal model with molecular ratio of 2:1 has higher value of binding energy, implying that the intermolecular interaction is stronger and this energetic cocrystal model is more stable. The engineering moduli (bulk modulus, shear modulus, and tensile modulus) of CL-20/bicyclo-HMX energetic cocrystal models are decreased, while Cauchy pressure is increased, indicating that the energetic cocrystal has better mechanical properties than CL-20. The energy density of CL-20/bicyclo-HMX cocrystal explosive is lower than pure CL-20, but much higher than bicyclo-HMX, the energetic cocrystal with molecular ratio of 10:1 ~ 2:1 can be regarded as potential candidate for high energy density compound (HEDC).

The process of midazolam ring closure was studied from the thermodynamic and kinetic points of view by means of quantum-chemical methods. B3LYP/6–311 + + G(d,p) model was employed for gas phase and water environment (polarizable continuum model) calculations. It was concluded that the reaction rate determining step is the first step—carbinolamine formation from amine and carbonyl ends of the opened benzodiazepine ring. The Gibbs free energy of activation was calculated as 35.1 kcal/mol for gas- phase and 33.9 kcal/mol for water environment. Intrinsic reaction coordinate calculations were performed to verify that the transition state really connects the substrate and product. Thermodynamically, this reaction is endoergic with Δ G = 9.6 kcal/mol for gas phase and 10.0 kcal/mol for water environment. However, the next step—carbinolamine protonation with immediate water molecule loss is expected to be fast and activation barrierless, which enables further progress of the ring closure, despite the positive Δ G of the fist step. Next, the protonated imine undergoes deprotonation to final closed ring, pharmacologically active molecule of midazolam. The whole chain of reaction is exoergic with Δ G equal to − 5.6 kcal/mol for gas phase and − 7.7 kcal/mol for water environment. In order to understand the role of other than benzodiazepine/imidazole molecular fragments on the ring closure process, a model was build which contains only benzodiazepine and imidazole rings. The activation barrier for the carbinolamine formation of the model is similar to midazolam in the gas phase but higher by about 10 kcal/mol for water environment. The most interesting difference is however that for the model, the carbinolamine formation step is exoergic with Δ G equal to − 2.2 kcal/mol for gas phase and − 1.8 kcal/mol for water environment. This difference can be connected to complicated conformational shape of the midazolam molecule, which during the ring closure undergoes unfavorable deformations with accompanying rise of the energy of the molecule. The protonation sites for both midazolam and the model were also studied. In the case of midazolam, the preferred protonation site is the imidazole ring nitrogen atom, but in the case of the model it is the benzodiazepine ring nitrogen atom. The aromaticity of the 5- and 7-membered rings were analyzed using two aromaticity—HOMA and pEDA. It follows that larger stability of the cation protonated at the benzodiazepine ring is accompanied with substantial increase of the 7-ring aromaticity in the model of midazolam. The complexes of midazolam and its model with a water molecule were analyzed because they are needed for evaluation of the energy of the whole process of ring closure. In the case of midazolam, the water molecule preferentially connects to imidazole ring, but in the case of the model, complexes with both imidazole and benzodiazepine rings have similar stability.

The recent study is focused on the exploration of properties related to the optical as well as nonlinear optical (NLO) applications by doping of Calix surface (C4Ps) with alkali metals (Li, Na, and K) doped exohedrally and alkaline earth metals (Be, Mg, and Ca) endohedrally. B3LYP/6-311G (d, p) is run down to investigate geometrical and associated optoelectronic prioperties of Be-C4Ps-Li (C4Ps1), Be-C4Ps-Na (C4Ps2), Be-C4Ps-K (C4Ps3), Mg-C4Ps-Li (C4Ps4), Mg-C4Ps-Na (C4Ps5), Mg-C4Ps-K (C4Ps6), Ca-C4Ps-Li (C4Ps7), Ca-C4Ps-Na (C4Ps8), and Ca-C4Ps-K (C4Ps9). The hyperpolarizabilities, electron density distribution map (EDDM), frontier molecular orbitals (FMOs), electrostatic potential (ESP), natural bonding orbital (NBO), dipole moment (µ), transition density matrix (TDM), non-covalent interaction (NCI), absorption maximum (max), density of states (DOS), interaction energy (Eint), transition density matrix (TDM), and vertical ionization energy (VIE) of various calix surface-based complexes were studied. Doping strategy used for all complex systems drastically altered charge transfer (CT) characteristics for example, lowering band gap (Eg) as well as boosting absorption to 1096 nm when compared to pure C4Ps with the dipole moment of 4.36 Debye and \({\lambda }_{\mathrm{max}}\) at 604 nm. Due to their lowest excitation energy, C4Ps1-C4Ps9 demonstrated a considerable increase in linear polarizability and first hyperpolarizability (αo 427.4–728.8au and βo 4949–122,390.6au) as compared to C4Ps surface (αo253au and βo524.7au). The use of C4Ps to dope alkali-alkaline earth metals is advantageous for developing future nanoscale devices, with a focus on the harmony of Calix surface with alkali-alkaline earth metals as well as their effects on NLO characteristics.

Pseudomonas aeruginosa is an opportunistic pathogen, having complicated quorum sensing (QS) system utilizing multiple signals and receptors to coordinate virulence and pathogenicity. N-acyl-homoserine-lactones (AHLs) are the most common autoinducers responsible for regulation of QS-mediated virulence gene expression. There are four QS systems in P. aeruginosa among which the LasI/R and RhlI/R systems are regulated by 3-oxo-C12-HSL and C4-HSL respectively. They play a major role in host-associated pathogenesis. The LasR and RhlR binding specificity to cognate or non-cognate HSLs influences the QS-mediated responses. Here, we used computational approaches to consolidate the interaction of different types of HSLs produced by P. aeruginosa with LasR and RhlR receptors. To explore the binding affinity, fourteen different AHLs were subjected for molecular docking analysis with LasR and RhlR receptors. The RhlR was modelled using MMseqs2 in ColabFold: Alpha fold 2. Further, to validate the stability and interaction mechanism, molecular dynamic simulations was performed with the top docked six HSLs for 100 ns. In docking results, apart from 3-oxo-C12-HSL and C4-HSL, other HSLs such as C16-HSL and C6-HSL showed better binding affinity towards LasR and RhlR proteins, respectively. Further validation by molecular dynamic simulations showed that 3-oxo-C10-HSL and 3-oxo-C6-HSL formed stable complex with LasR and RhlR, respectively. Our comprehensive in silico study results may provide promising targets for development of anti-QS drugs against Las/Rhl QS systems.

The isoquinoline nucleus is the fundamental structure of many natural and synthetic biologically active substances. This scaffold is found in a variety of compounds, including antihypertensive agents, anesthetics, and vasodilators. In the present work, the synthesis and antibacterial activity of novel 3-amino-1,2-dihydroisoquinoline derivatives have been reported. Theoretical calculations were performed to get insights into the molecular geometry and electronic properties of the synthesized compounds. The antibacterial activity of all compounds has been evaluated against five different bacteria strains and found potentially effective antibacterial agents. Among them, compound 3a was found to exhibit MIC value less than 0.25 mg/mL against Staphylococcus aureus, while compound 3b exhibits MIC value less than 0.25 mg/mL for both strains Staphylococcus aureus and Klebsiella pneumonia. The docking study revealed a good affinity toward the DNA gyrase enzyme. Furthermore, in silico ADME calculations revealed that all compounds had favorable pharmacokinetic properties.

Structural properties of the two ν-carrabiose disaccharide derivatives, d-galactpyranosyl-4-sulfate-(β-1,4)-d-galactopyranosyl-2,6-disulfate, and d-galactopyranosyl-2,6-disulfate (α-1,3)-d-galactopyranosyl-4-sulfate in acidic form or neutralized by monovalent cations Na+, K+, and Li+ are investigated. The effect of substitutions by carbocations, toluene, di-toluene, or metallocene on the occurrence of complexation was also examined. The calculations were carried out using the density functional theory method (DFT) in order to examine the nature of the complexation in the different cases. The preferred structures of these two disaccharide derivatives were determined in the gas phase after making iso-energetic maps. Parameters describing reactivity were calculated on all the studied molecules to better understand the behavior of this type of molecules. The intramolecular hydrogen bonds were useful to explain the stability of the considered systems. Frontiers orbitals and molecular electrostatic potential surfaces (MESP) were then analyzed to get information on the polarity and the reactivity of each molecule and were in agreement with the reactivity studies and it has been found that these substitutions strongly influence the HOMO and LUMO energies. In addition, parameters such as chemical potential, hardness, electrophilic power, softness, and empirical nucleophilic index were calculated. In order to quantify the effect of these substitutions on the complexation, the thermodynamic parameters were determined and allowed us to suggest that the addition of carbocations (hydrophobic chains) weakens the solvation Gibbs energy.

The mechanism of the condensation reaction of Al(OH) 4 − with D-gluconate is considered as a starting point in understanding the impact of organic substances on the Bayer process for obtaining alumina from bauxitic ores. Density functional theory (DFT) with a solvation model is used to study a model system of the different complexes formed between D-gluconate molecule and Al(OH) 4 − with monodentate or bidentate structures. The different mechanisms are studied to determine the most favorable pathway for the formation of the model complex. The DFT results show that the D-gluconate model forms an oxo bridge with aluminum through a first associative condensation step involving a pentacoordinated aluminum bonded to the carbon adjacent to the carbonyl of the ligand, and then a second bond is formed through a similar mechanism to obtain the most favorable bidentate structure. The rate-limiting activation barrier of the most favorable path is found to be 16.9 kcal mol −1 with density functional and 6.5 kcal mol −1 with CCSD(T) on geometries optimized with DFT and dispersion correction. The reaction energy for the preferred mechanism in solution is − 2.3 kcal mol −1. These results are in agreement with experimental observations, proposing the formation of bidentate Al(OH) 4 − with D-gluconate through condensation reactions in a strongly alkaline medium.