Chromodulin is an oligopeptide that has an essential role for the flawless functioning of insulin. Although the precise sequence of the constituent amino acid residues and the 3D structure of the molecule has not yet been deciphered, it is known that chromodulin contains only four amino acids in the ratio of Glu^–: Gly: Cys: Asp^– = 4: 2: 2: 2. An indispensable part for the integrity of the molecule in its active (holo-) form are four chromium cations (hence the name) in the oxidation state of 3+, positioned in two metal binding sites containing one and three Cr³⁺ ions. Experimental works provide some hints/clues concerning the structure of the metal centers, although their exact composition, type and arrangement of metal ligating entities remain enigmatic. In the current study, we endeavor to unveil possible structure(s) of the Cr³⁺ loaded binding sites by strictly following the evidence provided by the experimental data. Well-calibrated in silico methodology for optimization and evaluation of Gibbs free energies is applied and gives strong premises for reliably deciphering the composition/structure of chromodulin metal binding sites. Additional computations reveal the advantage of choosing Cr³⁺ over other tri- (Fe³⁺) and divalent (Fe²⁺, Mg²⁺ and Zn²⁺) biogenic ions for securing maximum stability of the metal-occupied binding sites.

The impact of thermal treatment for roasting on pine nuts from two geographical regions in Russia (Vladivostok and Baikal) was studied. They were roasted at 180 °C for 20 min in an oven. The aim was to establish the changes that occurred in the chemical (proteins, lipids, carbohydrates, ash, fibers), lipid composition (fatty acids, tocopherols, sterols, phospholipids), and physicochemical characteristics (peroxide value, acid value, iodine value, conjugated dienes and trienes) after roasting of the pine nuts. The results showed that the composition of the raw and roasted nuts differed (p < 0.05). Significant differences (p < 0.05) were observed in the oxidative stability of raw and roasted nuts from Baikal and, the content of unsaponifiable substances and sterols in the nut oil from Vladivostok. The roasting process influences the isolated oils from pine nuts as the chemical and lipid composition changes of oils from Baikal are significant (p < 0.05). Both raw and roasted pine nuts have high energy value, protein content, and good health benefits and can be consumed either way. Overall, it was established that the roasting of pine nuts had little impact on their lipid composition; the nuts could also be a source of lipid-soluble bioactive components and might have health–promoting effects.

Isatin derivatives have been at the forefront of pharmaceutical research, displaying a wide range of biological activities, including antioxidant, antimicrobial, and anticancer properties. In this study, twelve isatin-pyridine Schiff bases were evaluated using density functional theory (DFT) methods to examine the influence of pyridyl ring orientation (2-, 3-, and 4-aminopyridine) and C6-halogen substitution (F, Cl, Br) on electronic structure and reactivity. Frontier molecular orbitals and global reactivity descriptors were calculated to evaluate donor–acceptor properties, charge-transfer ability, and electronic stability. The 2-aminopyridine derivatives display the highest occupied molecular orbital (HOMO) energies, lowest unoccupied molecular orbital (LUMO) energies, and smallest energy gaps. Chlorine- and bromine-substituted derivatives show enhanced electrophilicity, electronegativity, and ∆N _max , while fluorine has minimal influence. DFT analysis reveals that 6-chloro-3-(2-pyridylimine)-indole-2-one and 6-bromo-3-(2-pyridylimine)-indole-2-one are the most promising candidates, as their electronic features are consistent with enhanced biological activity. These findings provide a basis for the rational design of next-generation isatin-Schiff bases with optimized reactivity and improved biological potential.

Histone deacetylase inhibitors (HDACi) are an emerging class of epigenetic anticancer drugs that exert their activity through coordination to the catalytic Zn²⁺ ion within the active site of histone deacetylases (HDACs). Due to the limited isoform-selectivity of hydroxamic acid-based inhibitors, benzamide-based HDACi (BBHDACi) have been developed as subtype-selective alternatives. Clinically relevant representatives include Chidamide, Entinostat, Mocetinostat, Zabadinostat, and Tacedinaline. Although these compounds share a conserved o-aminoanilide zinc-binding group (ZBG), they differ in linker and cap region structure, raising questions regarding their intrinsic Zn²⁺ affinity and coordination behavior. Herein, density functional theory (DFT) calculations were performed at the B3LYP/6-311++g(d,p) level of theory combined with the PCM solvation in methanol (ε = 33) and water (ε = 78). Geometry optimization confirmed that the trans (E) isomer of Chidamide is thermodynamically preferred. Coordination studies showed that the remaining BBHDACi adopt stable geometries, with the o-aminoanilide group preferentially forming tetracoordinated complexes that are more stable than hexacoordinated ones in polar media. Interestingly, calculated substitution free energies differed by less than ± 2 kcal.mol⁻¹, indicating nearly identical intrinsic Zn²⁺ affinities across the series. These results suggest that the ZBG contributes similarly to metal coordination across all BBHDACi, whereas the overall binding strength is mainly governed by interactions of the linker and cap regions rather than by the conserved zinc-binding group itself.

HDAC8 is a histone deacetylase enzyme that plays a key role in the development of various diseases in humans, including cancers, neurodegenerative diseases, and alcohol use disorder. Although HDAC8 is classified as a Zn²⁺-dependent metalloenzyme, available data regarding the affinity of other biologically relevant ions, such as Fe²⁺, Ni²⁺, Co²⁺, and Mg²⁺, for the HDAC8 enzyme active site remain unclear and contradictory. The mechanism by which these ions compete with Zn²⁺ for the HDAC8 active site is not well understood. In this study, we performed density functional theory (DFT) calculations at the B3LYP/6-31+G(d) level of theory, combined with polarizable continuum model computations (PCM) in water (ε = 78) and methanol (ε = 32). The results show that Zn²⁺ remains the thermodynamically preferred cofactor across all modeled reactions. Although Fe²⁺ and Co²⁺ gain partial stabilization upon increasing coordination number, the associated entropic and desolvation penalties prevent them from outcompeting Zn²⁺ under physiologically relevant conditions. Only a limited number of substitution reactions for Fe²⁺ and Co²⁺ yield ∆G values near thermodynamic neutrality, and only in specific coordination states. In contrast, all modeled Ni²⁺ substitution reactions are unfavorable, and Mg²⁺ is strongly excluded from the HDAC8 active site in all reactions. The resulting metal preference hierarchy—Zn²⁺ > Co²⁺ ≈ Fe²⁺ > Ni²⁺ > Mg²⁺—supports experimental observations and clarifies the intrinsic selectivity of the HDAC8 enzyme towards Zn²⁺. These insights provide a molecular basis for understanding HDAC8 metallo-regulation and may guide the rational design of novel, isoform-specific HDACi with improved binding properties.

Bexarotene is a clinically approved anticancer agent belonging to the retinoid class. Integrating the retinoid scaffold with a hydrazone moiety represents a promising strategy for modulating electronic properties relevant to receptor binding and desired biological activity. However, the electronic effects of halogen substitution within the retinoid–hydrazone framework have not been systematically studied. To address this gap, this study investigates the effects of substituent position, halogen type, and halogen load on the electronic structure and reactivity of a series of bexarotene-derived hydrazones. Density functional theory (DFT) calculations were carried out for six bexarotene–hydrazone derivatives (V1–V6), enabling the evaluation of frontier molecular orbital energies and global reactivity descriptors. In the series, V2 emerged as the strongest electron acceptor, demonstrating the highest electronegativity, the largest electrophilicity index, and the lowest unoccupied molecular orbital (LUMO) energy. The para -bromo analogue V4 displayed a similarly narrow highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO–LUMO) gap, although it demonstrated more donor-like behavior. The dichloro derivative V3, on the other hand, had the widest energy gap and the highest hardness and was recognized as the most electronically stable derivative. The ortho -chloro derivative V6 showed strong similarity to V3 in several descriptors, showing that substituent position can rival the number of halogens in determining reactivity. Overall, these electronic patterns provide a basis for future drug design, demonstrating how targeted substituent modification within the bexarotene–hydrazone scaffold can guide the development of new molecules with more favorable physicochemical properties.