Goran A. Bogdanović

Accessible-volume normalization overcomes bias in CSD data. Aligned with the energy profile, it shows that although fewer structures exist at small offsets, small horizontal offsets are geometrically preferred.

Compounds containing the α,β-unsaturated carbonyl (ketovinyl) moiety exhibit a wide range of bioactive properties, which give them a distinctive role in contemporary drug design. In this study, high-resolution X-ray diffraction analysis was employed to investigate the electron density distribution of 4-(2,4-Di-i-Pr-phenyl)-4-oxo-2-butenoic acid (DIPBA), which has demonstrated antiproliferative activity against various malignant cells in vitro. This analysis focuses on the electrostatic behavior of the ketovinyl moiety, which represents the core of reactivity and bioactivity of these kinds of Michael acceptors, enabling them to function as electrophiles that can bind to cellular thiols. The reactivity of DIPBA is presented by the structural analysis of the corresponding thio-adduct with thioglycolic acid. Because DIPBA incorporates diverse functionalities that form an extensive network of noncovalent interactions, these features are thoroughly examined through the deformation electron density, electrostatic potential, and topological analyses. The specific electrostatic properties, and the variety of noncovalent interactions in the crystal packing, suggest that this molecule can achieve selective recognition while forming stable contacts with its environment. By integrating the experimental charge density of DIPBA and the structural analysis of its thio-adduct with computational docking and molecular dynamics simulation, we trace a plausible pathway of an α,β-unsaturated carbonyl compound from the crystal to the biological environment.

In recent years, compounds from the Schiff base group have been intensively studied for their biological activities. Accordingly, a series of Schiff bases were synthesized from substituted aromatic aldehydes (5-chlorosalicylaldehyde) and differently substituted aromatic amines and their antimicrobial activities were evaluated. The molecular identity of compounds was confirmed using various spectroscopic techniques, such as IR and NMR spectroscopy and elemental analysis, and the molecular structure of compound 3k was determined by single-crystal X-ray analysis. The antimicrobial activity of 3a–3k compounds was examined in sixteen microorganisms (five species of bacteria and eleven species of fungi) using the microdilution method. Regarding antibacterial activity, a remarkable MIC value (0.0098 mg mL⁻¹) and, therefore, the best activity was displayed against Proteus mirabilis for 3e, which is even stronger than the most frequently used antibiotic medications. 3f showed the best antifungal activity against Microsporum gypseum, which is stronger than standard antimycotic fluconazole, and is also an important result considering that Microsporum gypseum can cause dermatophytosis in both humans and animals.

Two series of new ferrocenyl pyrazolines have been synthesized by the reaction of ferrocenyl chalcones and their analogues with hydrazine hydrate in the presence of corresponding carboxylic acid. Single‐crystal X‐ray crystallographic data were used for detailed analysis of the interesting versatility of four compounds in the formation of intermolecular interactions. The analysis revealed an excellent structural flexibility of the present ferrocenyl pyrazoline molecules for the non‐covalent interactions, with a particular contribution of the ferrocene units. In addition, for comparison with crystallographic findings, we investigated the protective effect of all compounds on DNA against hydroxyl and peroxyl radicals induced by Fe²⁺, H₂O₂, and 2,2′‐azobis(2‐amidinopropane) dihydrochloride (AAPH). The results indicated that all compounds showed rather similar DNA protective activity, which was comparable with quercetin as a well‐known protective compound. This similarity in antigenotoxic action could be explained by the established excellent structural flexibility of ferrocenyl pyrazolines for the formation of different intermolecular interactions as important structural property for molecular recognition.

The reaction of thiosemicarbazide and sodium pyruvate has been thoroughly studied and the novel crystal form of pyruvic acid thiosemicarbazone (H2pt) and its sodium salt was obtained. Compounds were characterized by IR spectra, melting points, elemental analysis, conductometric measurements and single-crystal X-ray analysis. A detailed comparative analysis of crystal structures of these compounds is given, as well as comparison with some of the earlier known complexes containing H2pt. The two novel crystal structures exhibit notably different hydrogen bonding patterns, mutually and in comparison with previously reported crystal form of H2pt. All crystal structures are stabilized by extensive network of N?H???O, O?H???O and N?H???S hydrogen bonds. The cyclic hydrogen bonding motif involving the thioureido moieties of the ligand is the only one which repeats in each structure.

Coronavirus outbreak is still a major public health concern. The high mutation ability of SARS-CoV-2 periodically delivers more transmissible and dangerous variants. Hence, the necessity for an efficient and inexpensive antiviral agent is urgent. In this work, pyrazolone-type compounds were synthesised, characterised using spectroscopic methods and theoretical tools, and evaluated in silico against proteins of SARS-CoV-2 responsible for host cell entry and reproduction processes, i.e., spike protein (S), M^pro, and PL_pro. Five of twenty compounds are newly synthesised. In addition, the crystal structure of a pyrazolone derivative bearing a vanillin moiety is determined. The obtained in silico results indicate a more favourable binding affinity of pyrazolone analogues towards M^pro, and PL_pro in comparison to drugs lopinavir, remdesivir, chloroquine, and favipiravir, while in the case of S protein only lopinavir exerted higher binding affinity. Also, the investigations were performed on ACE2 and the spike RBD-ACE2 complex. The obtained results for these proteins suggest that selected compounds could express antiviral properties by blocking the binding to the host cell and viral spreading, also. Moreover, several derivatives expressed multitarget antiviral action, blocking both binding and reproduction processes. Additionally, in silico ADME/T calculations predicted favourable features of the synthesised compounds, i.e., drug-likeness, oral bioavailability, as well as good pharmacokinetic parameters related to absorption, metabolism, and toxicity. The obtained results imply the great potential of synthesised pyrazolones as multitarget agents against SARS-CoV-2 and represent a valuable background for further in vitro investigations.

A simple method has been developed for the chemoselective synthesis of ferrocene-containing Rauhut–Currier adducts from 1-ferrocenyl-2-nitroethene and vinyl ketones catalyzed by triphenylphosphine.