Protein kinases are key enzymes in many signal transduction pathways, and play a crucial role in cellular proliferation, differentiation, and various cell regulatory processes. However, aberrant function of kinases has been associated with cancers and many other diseases. Consequently, competitive inhibition of the ATP binding site of protein kinases has emerged as an effective means of curing these diseases. Over the past three decades, thousands of protein kinase inhibitors (PKIs) with varying molecular frames have been developed. Large-scale data mining of the Protein Data Bank resulted in a database of 2139 non-redundant high-resolution X-ray crystal structures of PKIs bound to protein kinases. This provided us with a unique opportunity to study molecular determinants for the molecular recognition of PKIs. A chemoinformatic analysis of 2139 PKIs resulted in findings that PKIs are “flat” molecules with high aromatic ring counts and low fractions of sp³ carbon. All but one PKI possessed one or more aromatic rings. More importantly, it was found that the average weighted hydrogen bond count is inversely proportional to the number of aromatic rings. Based on this linear relationship, we put forward the exchange rule of hydrogen bonding interactions and non-bonded π-interactions. Specifically, a loss of binding affinity caused by a decrease in hydrogen bonding interactions is compensated by a gain in binding affinity acquired by an increase in aromatic ring-originated non-bonded interactions (i.e., π–π stacking interactions, CH–π interactions, cation–π interactions, etc.), and vice versa. The very existence of this inverse relationship strongly suggests that both hydrogen bonding and aromatic ring-originated non-bonded interactions are responsible for the molecular recognition of PKIs. As an illustration, two representative PKI–kinase complexes were employed to examine the relative importance of different modes of non-bonded interactions for the molecular recognition of PKIs. For this purpose, two FDA-approved PKI drugs, ibrutinib and lenvatinib, were chosen. The binding pockets of both PKIs were thoroughly examined to identify all non-bonded intermolecular interactions. Subsequently, the strengths of interaction energies between ibrutinib and its interacting residues in tyrosine kinase BTK were quantified by means of the double hybrid DFT method B2PLYP. The resulting energetics for the binding of ibrutinib in tyrosine kinase BTK showed that CH–π interactions and π–π stacking interactions between aromatic rings of the drug and hydrophobic residues in its binding pocket dominate the binding interactions. Thus, this work establishes that, in addition to hydrogen bonding, aromatic rings function as important molecular determinants for the molecular recognition of PKIs. In conclusion, our findings support the following pharmacophore model for ATP-competitive kinase inhibitors: a small molecule features a scaffold of one or more aromatic rings which is linked with one or more hydrophilic functional groups. The former has the structural role of acting as a scaffold and the functional role of participating in aromatic ring-originated non-bonded interactions with multiple hydrophobic regions in the ATP binding pocket of kinases. The latter ensure water solubility and form hydrogen bonds with the hinge region and other hydrophilic residues of the ATP binding pocket.

Accurate modeling of nonbonded interactions between protein kinases and their small molecule inhibitors is essential for structure-based drug design. Quantum chemical methods such as density functional theory (DFT) hold significant promise for quantifying the strengths of these key protein–ligand interactions. However, the accuracy of DFT methods can vary substantially depending on the choice of exchange–correlation functionals and associated basis sets. In this study, a comprehensive benchmarking of nine widely used DFT methods was carried out to identify an optimal approach for quantitative modeling of nonbonded interactions, balancing both accuracy and computational efficiency. From a database of 2139 kinase-inhibitor crystal structures, a diverse library of 49 nonbonded interaction motifs was extracted, encompassing CH–π, π–π stacking, cation–π, hydrogen bonding, and salt bridge interactions. The strengths of nonbonded interaction energies for all 49 motifs were calculated at the advanced CCSD(T)/CBS level of theory, which serve as references for a systematic benchmarking of BLYP, TPSS, B97, ωB97X, B3LYP, M062X, PW6B95, B2PLYP, and PWPB95 functionals with D3BJ dispersion correction alongside def2-SVP, def2-TZVP, and def2-QZVP basis sets. The RI, RIJK, and RIJCOSX approximations were used for selected functionals. It was found that the B3LYP/def2-TZVP and RIJK RI-B2PLYP/def2-QZVP methods delivered the best combination of accuracy and computational efficiency, making them well-suited for efficient modeling of nonbonded interactions responsible for molecular recognition of protein kinase inhibitors in their targets.

In this work, ZnO, SnO₂, and their mixed ZnO-SnO₂(25%) nanoparticles (NPs) were successfully green synthesized in a straightforward manner with a low-cost and environmentally friendly approach using a banana peel extract. The synthesized nanophotocatalysts were characterized using various techniques including FTIR, XRD, UV-Vis, TEM, SEM, BET, PL, EDS, and TGA. The characterization results showed that the ZnO and SnO₂ powders were crystallized in a hexagonal wurtzite and rutile-type tetragonal structures, respectively, and their mixed ZnO-SnO₂(25%) NPs contain both structures. Also, it was found that the addition of SnO₂ into the ZnO structure reduces the PL intensity of the latter, confirming better separation of electron/hole pairs. The average particle size of a ZnO-SnO₂(25%) NP photocatalyst was found to be 7.23 nm. The cationic dyes methylene blue (MB) and crystal violet (CV) as well as the anionic dyes naphthol blue black (NBB) and Coomassie brilliant blue R 250 (CBB) were employed as model dyes to assess the dye removal efficiencies of the biosynthesized nanophotocatalysts under sunlight. In all cases, the mixed ZnO-SnO₂(25%) NP photocatalyst showed much better photocatalytic activity than individual photocatalysts. The degradation percent of dyes using ZnO-SnO₂(25%) NPs ranged between 92.2% and 98%. The efficient photocatalytic activity of ZnO-SnO₂(25%) NPs is attributed to the effective charge separation and reduced electron/hole recombination rate. The kinetic study results conformed to a pseudo first-order reaction rationalized in terms of the Langmuir–Hinshelwood model. Furthermore, the results showed that the ZnO-SnO₂(25%) NP photocatalyst is highly stable and could be recycled several times without a noticeable reduction in its catalytic activity towards dye removal.

Poly(2-hydroxyethylmethacrylate)/Naproxen (NPX/pHEMA) and poly (2-hydroxypropyl methacrylate)/Naproxen (NPX/pHPMA) composites with different NPX content were prepared in situ by free radical photopolymerization route. The resulted hybrid materials were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning Electron microscopy (SEM), and X-ray diffraction (XRD). These composites have been studied as drug carrier systems, in which a comparison of the in vitro release dynamic of NPX between the two drug carrier systems has been conducted. Different factors affecting the performance of the release dynamic of this drug, such as the amount of Naproxen incorporated in the drug carrier system, the pH of the medium and the degree of swelling, have been investigated. The results of the swelling study of pHEMA and pHPMA in different media pHs revealed that the diffusion of water molecules through both polymer samples obeys the Fickian model. The “in vitro” study of the release dynamic of Naproxen from NPX/pHEMA and NPX/pHPMA drug carrier systems revealed that the higher percentage of NPX released was obtained from each polymer carrier in neutral pH medium, and the diffusion of NPX trough these polymer matrices also obeys the Fickian model. It was also found that the less the mass percent of NPX in the composites, the better its release will be. The comparison between the two drug carrier systems revealed that the pHEMA leads to the best performance in the release dynamic of NPX. Regarding Naproxen solubility in water, the results deducted from the “in vitro” study of NPX/pHEMA10 and NPX/pHPMA10 drug carrier systems revealed a very significant improvement in the solubility of NPX in media pH1 (2.33 times, 1.43 times) and 7 (3.32 times, 2.60 times), respectively, compared to those obtained by direct dissolution of Naproxen powder.

A series of poly(vinyl acetate-co-2-hydroxyethylmethacrylate)/acyclovir drug carrier systems (HEMAVAC) containing different acyclovir contents was prepared through bulk free radical polymerization of 2-hydroxyethyl methacrylate with vinyl acetate (VAc) in presence of acyclovir (ACVR) as the drug using a LED lamp in presence of camphorquinone as the photoinitiator. The structure of the drug carrier system was confirmed by FTIR and ¹HNMR analysis, and the uniform dispersion of the drug particles in the carrier was proved by DSC and XRD analysis. The study of the physico-chemical properties of the prepared materials, such as the transparency, swelling capacity, wettability and optical refraction, was carried out by UV–visible analysis, a swelling test and measurement of the contact angle and the refractive index, respectively. The elastic modulus and the yield strength of the wet prepared materials were examined by dynamic mechanical analysis. The cytotoxicity of the prepared materials and cell adhesion on these systems were studied by LDH assay and the MTT test, respectively. The results obtained were comparable to those of standard lenses with a transparency of 76.90–89.51%, a swelling capacity of 42.23–81.80% by weight, a wettability of 75.95–89.04°, a refractive index of 1.4301–1.4526 and a modulus of elasticity of 0.67–1.50 MPa, depending on the ACVR content. It was also shown that these materials exhibit no significant cytotoxicity; on the other hand, they show significant cell adhesion. The in vitro dynamic release of ACVR in water revealed that the HEMAVAC drug carrier can consistently deliver uniformly adequate amounts of ACVR (5.04–36 wt%) over a long period (7 days) in two steps. It was also found that the solubility of ACVR obtained from the release process was improved by 1.4 times that obtained by direct solubility of the drug in powder form at the same temperature.

Poly(ethylene-co-vinylalcohol) (E-VOH) and carbon nanotube-filled poly (vinyl alcohol-co-ethylene) (E-VOH/CNT) were used as membranes to separate benzene/cyclohexane mixtures by pervaporation technique. To reach this goal, E-VOH and E-VOH/CNT membranes were prepared by solvent casting method and characterized by differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The swelling tests were used to study the mass transfer of the benzene/cyclohexane mixture and their pure components. The separation by pervaporation process was carried out at 25 °C in which the effect of CNTs incorporated into E-VOH matrix and the initial concentration of benzene in the feed on the permeate flux, j, and separation factor, β, performance was investigated. The results obtained were very promising, in which the integration of CNTs through E-VOH chains increased the absorption area and raised the flux to 740 g/m²∙h. The separation factor increased to 9.03 and the pervaporation separation reached an index of 5942.2 g/m²∙h for the azeotropic mixture during 3 h of the separation process. In contrast, for the unfilled E-VOH membrane, it was found that these parameters were a rise of 280 g∙m⁻²∙h⁻¹, separation factor of 12.90 and pervaporation separation index of 3332.0 g/m²∙h, under the same conditions. Likewise, the calculation of the performance of the E-VOH/CNT membrane with regard to that of the unfilled membrane indicated 2.64 for the total flux and 0.70 for the separation factor. It was also revealed that the best compromise of the filled membrane in terms of total cumulative flux and separation factor is obtained for the feed containing the azeotropic mixture.