Solvent Effects Research Articles

Computational Characterization of the DAD Photoisomerization: Functionalization, Protonation, and Solvation Effects.

Photoswitches are becoming increasingly popular in pharmacology due to the possibility of modifying their activity with light. Hence, it is crucial to understand the photophysics of these compounds to identify promising light-activated drugs. We focused our study on DAD, an azobenzene derivative that, according to a previous experimental investigation, can restore visual function in blind mice due to trans-cis photoisomerization upon light absorption. With the present computational study, we aim to characterize the absorption spectrum of DAD, and to understand its photoisomerization mechanism by means of conformational search analysis, quantum mechanical (QM) and hybrid QM/continuum calculations, and classical molecular dynamics simulations. Moreover, we explored the effect of the derivation (DAD vs azobenzene), the protonation (DAD vs DADH22+, the two possible protonation states) and the solvation (vacuum vs water) on the photoisomerization. Similarly to azobenzene, we showed that the photoisomerization of both protonation states of DAD begin with the population of the bright S2 state. Then, it crosses to the S1 surface and relaxes along the rotation of the azo dihedral to a S1/S0 crossing point. The latter is close to a transition state that connects the trans and cis geometries on the ground state. Finally, our results suggested that amino derivation, nonprotonation and water solvation could improve the quantum yield of the photoisomerization.

Revealing the antioxidant properties of alkyl gallates: a novel approach through quantum chemical calculations and molecular docking.

This study investigates the antioxidant potential of alkyl gallates (C1-C10), focusing on the impact of alkyl chain length and solvent polarity on their antioxidant properties. Known for their biomedical relevance in mitigating oxidative stress, alkyl gallates' structure-activity relationships, particularly regarding chain length and environmental factors, still need to be explored. Key thermochemical parameters, including bond dissociation enthalpy (BDE), ionization potential (IP), proton affinity (PA), and electron transfer enthalpy (ETE), reveal that shorter alkyl chains (C1-C4) exhibit superior antioxidant activity. In contrast, longer chains (C5-C10) show reduced effectiveness due to steric hindrance and lower solubility in polar solvents. Molecular docking studies also demonstrated favorable binding interactions with vital biological targets, further reinforcing their antioxidant potential. Quantum chemical calculations were performed using Gaussian 16 with the B3LYP/6-311G(dp) basis set for geometry optimizations. Solvent effects were modeled using the integral equation formalism-polarized continuum model (IEF-PCM). Molecular docking studies were conducted using AutoDockTools 4.2, targeting Tyrosine Kinase Hck, Heme Oxygenase, and Human Serum Albumin to evaluate fundamental binding interactions. These computational methods provided insights into alkyl gallates' chemical reactivity and antioxidant efficiency, allowing for the rational design of more potent antioxidant compounds.

Structural, Solvent, and Temperature Effects on Protein Junction Conductance.

Cytochrome b562 is a small redox-active heme protein that has served as an important model system for understanding biological electron transfer processes. Here, we present a comprehensive theoretical study of electron transport mechanisms in protein-metal junctions incorporating cytochrome b562 using a multi-scale computational approach. Employing molecular dynamics (MD) simulations, we generated junction geometries for both vacuum-dried and solvated conditions, with the protein covalently bound to gold contacts in various configurations. Coherent tunneling, described by the Landauer-Buttiker formalism within the density functional theory (DFT) framework, is compared to the incoherent hopping charge transport mechanism captured by the semi-classical Marcus theory. The tunneling was identified as the dominant mechanism explaining the experimental data measured on the cytochrome b562 junctions, exhibiting exponential yet very shallow distance dependence. While the structural orientations and protein contacts with the electrodes influence the junction conductance significantly, the solvation effects are relatively small, affecting the electronic properties mostly via the adsorption arrangement. On the other hand, the considerable temperature dependence of the conductance was found strong only for hopping, while the tunneling current magnitudes remain practically unaffected and are a good indicator of the coherent mechanism in this case.

Polarity Gradient Solvent Confinement Membrane Cartridge to Broaden Metabolite Coverage of Plasma Untargeted Analysis.

Various polarity chemicals exist in complex samples, such as plasma; nontargeted comprehensive analysis naturally requires multiple polar-extracted solvents; consequently, the polarity of the solvent plays a crucial role in the extraction efficiency of analytes from complex samples. In the present study, based on the diffusion behavior and nanoconfinement effect of solvents in the nanoconfined space, the polarity gradient solvent confinement liquid-phase nanoextraction (PGSC-NLPNE) protocol aimed to perform a one-step nontargeted analysis of a wide range of metabolites in plasma was established. The continuously wide range of extracted solvent polarities on carbon nanofibers/carbon fiber (CNFs/CF) membranes was achieved using a mixture of hexane, dichloromethane, methanol, and water as nanoconfined solvents. The polarities (Log P) of gradient solvents ranged from -1.38 to 3.94. Correlational analyses indicated that metabolites with Log P values ranging from -1.90 to 3.84 were closely related according to similarity-intermiscibility theory. Coupled with a homemade modified guard column device, CNFs/CF membrane cartridge (CCMC), a PGSC-NLPNE-UHPLC-MS online protocol was established and applied in plasma untargeted analysis. By comparing metabolome coverage, reproducibility, and extraction recovery with protein precipitation and two-step liquid-liquid extraction commonly used in untargeted analysis, the PGSC-NLPNE-CCMC protocol demonstrated higher reproducibility and recovery. This protocol has shown great potential for ultrafast analysis of plasma untargeted metabolomics with broader metabolome coverage. It could be a potential tool to rapidly screen out valuable biomarkers related to diseases in the clinic.

Comprehensive Theoretical Insights on Spectroscopic Characterization, Solvent Effect (Polar and Nonpolar) in Electronic behavior, Topological Insights, and Molecular Docking Prediction of Taurolidine

In recent decades, sulfur-containing compounds have played a significant role in biological applications because of their unique biological and chemical characteristics. Taurolidine, a sulfur-containing derivative of the amino acid taurine, has been characterized theoretically utilizing Density Functional Theory (DFT) at the B3LYP approach along with a 6-311++G(d,p) basis set. The impact of solvents on electronic characteristics, Molecular electrostatic potential (MEP), and Fourier Molecular Orbital (FMO) in polar (water and ethanol) and nonpolar (toluene and chloroform) has been analyzed. The bond distances of S1-C16 and S1-C17 have been simulated at 1.817 Å and observed at 1.743 and 1.739 Å, respectively. These distances are increased compared to other bond distances due to the influence of sulfur atoms. The distinctive simulated vibrational wavenumbers of taurolidine revealed peaks for SO2, CH2, CN, and NH groups. The intramolecular interactions responsible for stabilizing the molecular structure of taurolidine have been addressed using NBO analysis shows significant stabilization energy from electron-donating lone pair oxygen O6 to antibonding S2-N10 with the stabilizing energy of 19.88 KJ/mol by the transition of LP(3)- σ*. The bonding characteristics and reactive sites (electron-rich and electron-poor) have been confirmed with Mulliken and MEP analysis. The carbons (C17 and C16) emphasize the increased negative potential due to the sulfonyl (SO2) group in the ortho position. The topological insights, ELF and LOL, were spotted using Multiwfn software, highlighting the localized and delocalized electron regions within the crystal structure. In addition, molecular docking was performed to predict the antagonist activity of taurolidine against β-catenin protein, yielding a binding energy of -6.86 KJ/mol, which confirms its antiproliferative property.

Effect of Solvent on the Structural and Morphological Properties of α-Fe2O3 Deposited at Different Temperatures Using Aerosol-assisted CVD in an In-house Built Setup

Effect of Solvent on the Structural and Morphological Properties of α-Fe2O3 Deposited at Different Temperatures Using Aerosol-assisted CVD in an In-house Built Setup

Antioxidant activity, enzyme inhibition, photoprotection, cytotoxicity, and phytochemical profiling of sea lavender (Limonium algarvense Erben) seed extracts for dermo-cosmetic use

BackgroundDespite sea lavender being a medicinal species, research on its seeds’ biological properties and chemical composition is unexplored. Thus, this study evaluated the effect of different extraction solvents on the biological activities and chemical profile of greenhouse-cultivated sea lavender seeds, aiming at their potential use as a dermo-cosmetic ingredient. Therefore, ethyl acetate, acetone, ethanol, and water extracts were examined for their antioxidant activity, enzyme inhibition, photoprotection, and cytotoxicity, followed by phytochemical analysis through spectrophotometric methods, further detailed by Ultrahigh-Performance Liquid Chromatography Coupled with Electrospray Ionization Mass/Mass Spectrometry (UHPLC-Esi-MS/MS).ResultsThe water extract demonstrated significant antioxidant activity, evidenced by low half maximal effective concentration (EC50) values in scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, reducing iron and chelating copper (296, 478, 230 and 678 µg/mL, respectively). The ethanol extract was more effective in inhibiting cosmetic-related enzymes, particularly elastase and hyaluronidase (2.18 and 3.21 µg/mL, respectively). The water and acetone extracts had the highest sun protection factors (23.2 and 18.9, respectively). All the extracts had nil to weak cytotoxicity (70–120% cell viability) towards mammalian cell lines. The water extract had the highest phenolics and condensed tannins (115 and 78.30 mg/g extract, respectively), while the ethanol contained the most flavonoids (62.73 mg/g extract). UHPLC-ESI–MS/MS analysis identified ethyl gallate, myricetin, rutin, and quercetin as major components of the ethanol extract, whereas myricetin-O-rutinoside isomers are predominant in the water extract.ConclusionsThese findings highlight the potential of greenhouse-cultivated sea lavender seeds as potential dermo-cosmetic ingredients, with ethanol and water extracts demonstrating superior biological activities and chemical profiles, significantly contributing to general skin health and protection.

Optimizing Nonaqueous Sodium–Polysulfide Redox-Flow Batteries: The Role of Solvation Effects with Glyme Solvents

Optimizing Nonaqueous Sodium–Polysulfide Redox-Flow Batteries: The Role of Solvation Effects with Glyme Solvents

A computational study on the detection properties of pristine, Al-, and Ga- doped Zn12O12 nanoclusters toward Deferiprone in gas and solvent phases

Electrochemical sensors have great potential in point-of-care diagnostic devices, benefiting from advancements in nanomaterials that enhance sensitivity and selectivity and reduce costs. This study theoretically investigates Deferiprone (DEF) sensing using pristine and aluminum – and gallium-doped Zn12O12 nanoclusters (AlZn11O12 and GaZn11O12) through a density functional theory (DFT) approach at the B3LYP-D level with a 6-311G (d, p) basis set. The results indicate DEF adsorption energies of −29.53 kcal mol−1 for Zn12O12, −42.19 kcal mol−1 for AlZn11O12, and −27.12 kcal mol−1 for GaZn11O12 in their most stable orientations. The adsorption of DEF significantly alters the energy gap (Eg) in the doped nanoclusters, highlighting the superior sensitivity of AlZn11O12 and GaZn11O12 for DEF detection. Transition theory calculations reveal a practical recovery time of 72.64 s for GaZn11O12, indicating favourable adsorption characteristics. Solvent effect studies show that the DEF/GaZn11O12 complex is stable in water, with a higher dipole moment reflecting increased water polarisation. UV-Vis analysis demonstrates that DEF adsorption on GaZn11O12 shifts the spectrum to higher wavelengths, indicating enhanced adsorption. Thus, GaZn11O12 is proposed as a promising candidate for DEF detection in both gas and solvent phases.

Synthesis of 3‑Chloroindoles via Palladium‐Catalyzed Chlorocyclization of Unmasked 2‑Alkynylanilines

Described herein is the discovery of a palladium‐catalyzed chlorocylization strategy for the synthesis of 3‑chloroindoles tolerated with a wide range of functional groups in moderate to excellent yields. In this transformation, the solvent effect is so important that only THF presents the positive effect. Furthermore, the present method provides an essay access to the N‐unprotected 3‐chloroindoles. A mechanism study showed that 2‐alkynlanilines were catalyzed by palladium to from corresponding indoles, followed by copper‐mediated oxidation chlorination to deliver the 3‐chloroindoles products.

TiO2/ZnWO3 with improved photocatalytic performance in the preparation of chromeno[4,3-b]chromenes

Chromeno[4,3-b]chromenes have shown potential as effective drugs against cardiovascular diseases, primarily due to their diverse biological activities, including anti-inflammatory and antioxidant properties. This study was conducted on a new heterojunction nanocomposite TiO2/ZnWO3 consisting of titanium dioxide (TiO2) and zinc tungstate (ZnWO3) with enhanced photocatalytic capability. TiO2/ZnWO3 nanophotocatalyst is characterized by FT-IR, XRD, DRS, SEM, and EDX and performed as an efficient nanophotocatalyst in the synthesis of chromeno[4,3-b]chromene derivatives. The research focused on the intricate interplay of the components, aiming to optimize the catalytic reactions under green-light irradiation. Through this investigation, insights were gained into the mechanistic pathways and the potential for improved yields in the formation of the desired chromene. TiO2 has the ability to absorb light and produce electrons and holes when exposed to the direct light; but to increase its photocatalytic activity, an additional component ZnWO3 is combined. Effect of photocatalyst amount, reaction time, temperature, and solvent as well as reusability of the nanocomposite are investigated. The research focused on the intricate interplay of the components, aiming to optimize the catalytic reactions under green-light irradiation. Through this investigation, insights were gained into the mechanistic pathways and the potential for improved yields in the formation of the desired chromene. TiO2 has the ability to absorb light and produce electrons and holes when exposed to the direct light; but to increase its photocatalytic activity, an additional component ZnWO3 is combined. Effect of photocatalyst amount, reaction time, temperature, and solvent as well as reusability of the nanocomposite are investigated.

The role of intra and intermolecular interactions on the conformational dynamics of 2-halo-1-phenylpropanols: Structure and solvent effects

Experimental and theoretical 3JHH scalar coupling constants allowed the identification of the conformational landscape of erythro (eX) and threo (tX) 2-halo-1-phenylpropanols (halo = F, Cl, and Br). NMR scalar coupling constants captured dynamics of the OC-C-X dihedral and OH rotameric states, in a dynamic and solvent-dependent equilibrium. The erythro series revealed a particular halogen-dependent equilibrium, which showed different sensitivity to the media, especially in acetone, where the eF populations were completely shifted. At the same time, threo showed a highly solvent-sensitive equilibrium. NBO calculations showed the importance of electron delocalization over steric and electrostatic effects to stabilize the preferred synclinal conformer in both diastereomers. A Principal Component Analysis (PCA) on the NBO stabilization energies pointed to a complex mixture of electronic delocalization happening simultaneously. Hyperconjugative interactions are significant, but they are not the only important effect. Non-covalent interactions were also identified through NCI surfaces. Hydrogen bonds and intramolecular C-X···π and CH···π interactions were proved to act differently in the two diastereomers, affecting their equilibria in different ways. Nuclear Overhauser (NOE) NMR experiments point to an intramolecular CH···π contact, while 1H NMR of the aromatic hydrogens evidence an intermolecular effect of acetone and DMSO on the phenyl ring. DFT with explicit solvation shows a solvent shell favoring intermolecular CH···π contacts, in agreement with the experiments. This thorough analysis revealed that intra- and intermolecular factors contribute to the preference for the synclinal conformer in the studied compounds.

A metabolomic analysis on the toxicological effects of the universal solvent, dimethyl sulfoxide

Dimethyl sulfoxide (DMSO) is a solvent used to dissolve a variety of organic compounds. It is presumed to be non-toxic at concentrations below 10 % v/v, although several studies have demonstrated that low dose DMSO exposure can alter cellular biochemistry. This study evaluated the toxicity of DMSO at 0.0002 % v/v to the Sydney Rock oyster, Saccostrea glomerata, following 7d of exposure. Metabolites were chosen as the toxicity endpoints because they can be used as energy sources and counteract contaminant-induced stress. Relative to seawater controls, exposure to DMSO caused a 74 % significant change in metabolites in the female digestive gland, including decreases in most amino acids, carbohydrates, nicotinamides, and lipids. The female gonad showed a 43 % significant change in metabolites, with decreases in amino acids and carbohydrates, but increases in lipids. The male digestive gland showed a 29 % significant change in metabolites, with increases in lipids. The decline in metabolites in the female digestive glands but not in males may be due to their differential metabolic demands. Furthermore, pathway impact analysis revealed that DMSO exposure altered energy metabolism, disturbed osmotic balance, and induced oxidative stress in oysters. Because the effects of DMSO are not uniform across gender and tissue, use of DMSO as a solvent will confound metabolomic experimental results when comparisons among sexes and/or tissues are integral to the experimental design. There is a risk of incomplete dissolution of contaminants unless carrier solvents are used. Therefore, in practice, a water control along with a solvent control is recommended for any experimentation.

Comparing effects of terpene-based deep eutectic solvent and solid microneedles on skin permeation of drugs with varying lipophilicity

Transdermal delivery of therapeutic molecules is often hindered by the properties of the skin, with the stratum corneum serving as the primary permeation barrier. To overcome this barrier, the integrity of the stratum corneum can be modified by chemical permeation enhancers, such as deep eutectic solvents (DESs), or by mechanically impairing the skin with microneedles (MNs). However, a systematic comparison between these strategies is currently lacking. Hence, this study examined the potential of DESs and MNs to promote the permeation and retention of drugs with varying lipophilicities – specifically, the hydrophilic drug metronidazole (logP ∼ 0), the moderately lipophilic drug lidocaine (logP ∼ 2.3), and the highly lipophilic drug clotrimazole (logP ∼ 5). A mixture of menthol and thymol was selected as a model terpene-based DES and delivery vehicle, while a DermaPen equipped with solid MNs was used to mechanically impair the skin. Permeation rates of model drugs applied to the skin with either DES, MNs, or both were compared to the rates determined for the drugs applied in control vehicles. Both strategies were found to compromise the skin barrier function, but their permeation-enhancing effect was dependent on the lipophilicity of tested model drug. The DES was most effective for the hydrophilic drug metronidazole, while the MNs were more effective in increasing the permeation of the highly lipophilic drug clotrimazole. For the moderately lipophilic drug lidocaine, neither the DES nor microneedles increased its permeation rate, as the drug permeated through the skin well on its own. Notably, the combination of both enhancement strategies did not result in significantly better permeation rates of the drugs compared to the individual approaches. In conclusion, both the terpene-based DES and solid MNs are effective strategies to enhance drug permeation through the skin, but our results suggest that the choice of strategy should be dictated by the drug’s lipophilicity. Moreover, from a permeation-enhancing perspective, there is no benefit in combining these two strategies.

Building hydrophobic substrate pocket to boost activity of laccase-like nanozyme through acetonitrile-mediated strategy

Nanozymes, as promising alternatives to natural enzymes, offer several advantages with biocatalytic functions but remain inferior in catalytic activity. It is crucial to focus on factors that affect the enzymatic activity of nanozymes and develop strategies to make them more competitive with natural enzymes. Herein, CuV2O5 nanorods are confirmed to own the intrinsic laccase-like activity, and an acetonitrile (MeCN)-mediated strategy is proposed for reaction acceleration by mimicking the enzymatic substrate pocket. In the presence of MeCN, the interaction between substrates and nanozymes gets efficiently promoted by the bridging function of cyano-group, where the utilization of Cu active sites is greatly improved due to a condensed hydrophobic substrate layer formed in the vicinity of CuV2O5 nanozyme by the solvent effect of MeCN. Theoretical calculations also disclose that the addition of MeCN endows 2,4-dichlorophenol (2,4-DP) with a lower free-energy barrier in adsorption and activation on the surface of CuV2O5 nanozyme. Benefiting from the improved activity, a sensitive colorimetric sensing platform for 2,4-DP is constructed with limit of detection as low as 0.48 μM. Our finding lays a theoretical foundation for achieving high-performance catalytical activity of the nanozymes based on the modulation of the reaction microenvironment, effectively alleviating the complex engineering process of nanozymes.

Effect of solvent in the solvothermal synthesis of nickel(II)-terephthalate complex

This research aims to replace the use of dimethylformamide (DMF) with a greener solvent in the solvothermal synthesis of nickel(II)-terephthalate complex. Effect of solvent on the crystallinity degree, thermal stability, and band gap energy of the synthesized complex are also studied. The synthesis was carried out using solvothermal method at 150 0C for 10 hours with a Ni(II) : terephthalate acid mol ratio of 1:1 in several H2O:DMF solvent compositions (1:0; 1:1; and 0:1). The precipitated products underwent characterization using ATR-IR, P-XRD, SEM, TGA, Surface Area Analyzer, and UV-DRS. Findings revealed the successful formation of the Ni(II)-terephthalate complex using three different solvent compositions (H2O/DMF = 1:0, 1:1, and 0:1). This suggests that the complex can be synthesized using more environmentally friendly solvents, potentially reducing or substituting the use of DMF solvent. However, the solvent affects the characteristics of the synthesized complex, in which green block microcrystalline solid was obtained when using water as the solvent, meanwhile green aggregates with lower crystallinity degree was precipitated out when using DMF or H2O-DMF. The Ni(II)-terephthalate complexes obtained from the H2O and H2O-DMF solvents are different to that of from the DMF solvent, but they both has identical powder diffraction pattern with previously reported compound of [Ni3(OH)2(C8H4O4)2(H2O)4].2H2O. Furthermore, the use of water as the solvent increase the crystallinity degree and thermal stability of the complex but the band gap energy of the synthesized Ni(II)-terephthalate complex compared to that of obtained from the DMF solvents.

Prediction of Redox Potentials for Ac, Th, and Pa in Aqueous Solution.

Density functional theory in conjunction with small core pseudopotentials and the associated basis sets was used to calculate potentials for multiple redox couples, covering a range of oxidation states for Ac (0 to III), Th (0 to IV), and Pa (0 to V) in aqueous solution. Solvation effects were incorporated using a supermolecule-continuum approach, with 30 water molecules representing two solvation shells, and the COSMO and SMD implicit solvation models. The calculated geometries for Ac(III), Th(IV), and Pa(V) were in reasonable agreement with the available experimental data. Using the COSMO model with the B3LYP functional, the calculated redox potentials were within ±0.2 V from experiment for most redox couples. Several pathways were explored for the Pa(V/IV) redox couple for different forms of Pa(V) and Pa(IV). Most Pa(V/IV) redox couples have very similar potentials, ranging from 0 to -0.4 V up to a pH of 1.4. At pH = 1.4, the potentials shift to values that are more negative than -0.7 V, reflecting the growing unfavorable nature of the redox process at higher pH levels. The calculated values for An(III/II) potentials were consistent with prior estimates and the available experimental data. The predicted redox potentials for An(II/I) were highly negative, as expected. For An(I/0) potentials, Th and Pa exhibited positive values, contrasting with the negative values calculated for Ac. The An+m/An(0) potentials agreed better with the experimental data when using the COSMO solvation model as compared to the SMD model.

Nuclear Quantum Effects Have a Significant Impact on UV/Vis Absorption Spectra of Chromophores in Water.

Despite the broadly acknowledged importance of solvationeffects on measured UV/Vis spectra in the context ofsolvatochromism or chemical reactions in solution, it is still an open challenge to calculate UV/Vis spectra with predictive accuracy. This is particularly true when it comes to theimpact of nuclear quantum effects on these experimentalobservables. In the present work, we calculate the UV/Visabsorption spectrum of indole in aqueous solution with acombination of a correlated wavefunction method for computing electronic excitation energiesand enhanced path integralsimulations for rigoroussampling of nuclear configurations includingthe quantum effects in solution.Aftervalidating our approach based on gas-phase benchmarking, we demonstrate that the lineshape ofthe spectrum measured in aqueous solution is quantitatively recovered,without the application of any shifting, scaling, or broadening,only after including nuclear quantum effects in additionto thermal fluctuations and solvation at ambient conditions.Our findings demonstrate that nuclear quantum effects are"visible" in UV/Vis spectra of chromophores measured in solution even at room temperature and, therefore, thatthey must be considered computationally to achieve predictive accuracy.

Nuclear Quantum Effects Have a Significant Impact on UV/Vis Absorption Spectra of Chromophores in Water

Despite the broadly acknowledged importance of solvation effects on measured UV/Vis spectra in the context of solvatochromism or chemical reactions in solution, it is still an open challenge to calculate UV/Vis spectra with predictive accuracy. This is particularly true when it comes to the impact of nuclear quantum effects on these experimental observables. In the present work, we calculate the UV/Vis absorption spectrum of indole in aqueous solution with a combination of a correlated wavefunction method for computing electronic excitation energies and enhanced path integral simulations for rigorous sampling of nuclear configurations including the quantum effects in solution. After validating our approach based on gas‐phase benchmarking, we demonstrate that the lineshape of the spectrum measured in aqueous solution is quantitatively recovered, without the application of any shifting, scaling, or broadening, only after including nuclear quantum effects in addition to thermal fluctuations and solvation at ambient conditions. Our findings demonstrate that nuclear quantum effects are "visible" in UV/Vis spectra of chromophores measured in solution even at room temperature and, therefore, that they must be considered computationally to achieve predictive accuracy.

Piperine analogues as dual inhibitors for antibacterial and antiarthritic properties through impact of ligands optimization, docking and water solvation

The prevalence of bacterial diseases poses a significant challenge because of how they can develop resistance to antibiotics and evade the human immune system, highlighting the need for novel therapeutic approaches. Bacterial infection leads to the degradation of bone tissue and the development of arthritis. This study investigates the antibacterial and antirheumatic properties of piperine analogues. Computational analyses, including molecular docking quantum chemical studies and ADMET analysis, are performed to screen out potential inhibitory compounds. A library of 100 ligands is obtained from PubChem and subjected to virtual screening using various filters, including pharmacophore properties, molecular docking, and toxicity prediction, to identify potential candidates. Four compounds, P1-P4, are selected for further investigation using quantum chemical methods. These compounds are subjected to quantum chemical spectroscopic analysis, including UV–visible and IR spectra. The molecular geometries are fully optimized. HOMO and LUMO orbitals including their energies are calculated to estimate intermolecular charge transfer properties Molecular docking results revealed “compound P3 displayed the highest binding affinity to both proteins, with binding energies of 9.0 kcal/mol and 9.8 kcal/mol for FtsZ and Neutrophil collagenase proteins, respectively”. The analysis of 2D and 3D interactions between the selected compounds and both proteins reveals the formation of three important hydrogen bonds between ligand P3 and the FtsZ protein, as well as two hydrogen bonds between P3 and the Neutrophil collagenase protein. Additionally, ligand P4 forms three hydrogen bonds with the Neutrophil collagenase protein. The small energy gap of 3.85 eV between the HOMO and LUMO of the optimized molecule Neutrophil collagenase indicates that the compound is among the category of soft compounds and biologically more active. As new insights, for the first time, we performed a comparative analysis of the energies of the docked and optimized ligands that reveal the docked ligands always possess higher energies which might be considered as energy-penalty during the docking process. This energy penalty is found to be −24, −22, −26 and −32 kcal/mol for FtsZ and −169, −40, −35 and −39 Kcal/mol for Neutrophil collagenase P1-P4, respectively. The orbital energy gap further decreases in solvation with water and increases its chemical reactivity. Under the solvation effect of water as solvent, the quantum computational results indicated enhanced molecular solubility and stability, which are critical factors for bioavailability. The researchers suggested that the combination of increased reactivity and better solubility ensures that the drug performs more effectively in biological environments, making it a more potent inhibitor for bacterial infections and arthritis. The molecular geometries including bond lengths and bond angles of all studied compounds were also influenced in a solvent environment.