Agnieszka Justyna Rybarczyk-Pirek

Cocrystal structures formed by trithiocyanuric acid (TTCA) and selected nitroimidazole derivatives, dimetridazole (DMZ·TTCA, C ₅ H ₇ N ₃ O ₂ ·C ₃ H ₃ N ₃ S ₃ ), tinidazole (TNZ·TTCA·MeOH, C ₈ H ₁₃ N ₃ O ₄ S·C ₃ H ₃ N ₃ S ₃ ·CH ₃ OH), ornidazole (ONZ·TTCA·MeOH, C ₇ H ₁₀ ClN ₃ O ₃ ·C ₃ H ₃ N ₃ S ₃ ·CH ₃ OH, and ONZ·TTCA·H ₂ O, C ₇ H ₁₀ ClN ₃ O ₃ ·C ₃ H ₃ N ₃ S ₃ ·H ₂ O) and ronidazole (RNZ·TTCA and 2RNZ·2TTCA, both C ₆ H ₈ N ₄ O ₄ ·C ₃ H ₃ N ₃ S ₃ ) were investigated to identify recurring drug–coformer aggregation patterns and factors determining supramolecular architecture. Structural analysis showed that TTCA adopts two principal supramolecular motifs: the hydrogen-bonded R ₂ ² (8) dimer and linear chain assemblies. Two dominant drug–coformer binding schemes were identified. The first involves N—H...N hydrogen bonding in the para position relative to the TTCA dimer, leading to four-molecule assemblies, which are accompanied by heteronuclear hydrogen bonding in the ortho position. The second motif is associated with TTCA linear chains, where drug molecules are linked through N—H...N interactions and further stabilized by direct intermolecular or solvent-mediated hydrogen bonding. The polymorphic structure 2RNZ·2TTCA combines both supramolecular strategies within a single-crystal architecture. Hirshfeld surface analysis and intermolecular energy calculations confirmed the importance of hydrogen-bond competition in determining the crystal packing and supramolecular organization in TTCA-based cocrystals.

The presented paper describes a regio- and stereoselective method for synthesizing of chiral amino alcohol derivatives from simple, readily available substrates such as chiral epoxides and chiral aziridines.

Four new crystal structures of trithiocyanuric acid (TTCA) with diazine derivatives have been determined, revealing key N–H⋯S interactions that stabilize molecular aggregates. TTCA forms two types of chains—linear and zigzag—each with distinct structural characteristics. Geometry and Hirshfeld surface analyses, supported by quantum-theoretical calculations, demonstrate that both chain arrangements are equally feasible, arising from inherent preferences in the crystal's structural organization. The critical role of intermolecular hydrogen bonds, particularly those involving amine groups as proton donors, in stabilizing these cocrystals is highlighted. To analyze the energy parameters, we applied the many-body extension of the supramolecular interaction energy approach for chain complexes in their crystal-state geometry, allowing decomposition of the interaction energy into two- and many-body contributions. The prevalent hydrogen bonding synthon, R² ₂(8), which forms both linear and zigzag chain structures, was found to be crucial in stabilizing the TTCA aggregates.

Amines significantly accelerate iodide substitution in CpFe(CO)₂I with phosphines.

Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)₂AgNO₃], [(MTZ)₂Ag]₂SO₄, [Ag(MCZ)₂NO₃], [Ag(MCZ)₂BF₄], [Ag(MCZ)₂SbF₆] and [Ag(MCZ)₂ClO₄] (MTZ—metronidazole; MCZ—miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC₅₀ values against the A375 line were demonstrated by [Ag(MCZ)₂NO₃] and [(MTZ)₂AgNO₃]. The compound [(MTZ)₂AgNO₃] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L.

X-ray diffraction studies reveal that pyrazine-2-thiol undergoes condensation to 2,2′-dithiobispyrazine [systematic name: 2-(pyrazin-2-yldisulfanyl)pyrazine], C₈H₆N₄S₂ (I), under aerial conditions. In the molecule of I, the pyrazine rings are arranged in an almost perpendicular manner, with an absolute value of the C—S—S—C torsion angle of −91.45 (6)°. A search in the Cambridge Structural Database confirmed that such a conformation is typical for disulfide compounds. Three different rotamers of disulfide I were studied using quantum theoretical studies. The rotamer of lowest energy was observed in the crystalline state in the structure stabilized by hydrogen-bond, chalcogen-bond and stacking interactions. Further quantum chemical computations confirm that 2,2′-dithiobispyrazine can react according to the S_N2 mechanism.

In these studies, we designed and investigated cyto- and genotoxic potential of five ruthenium cyclopentadienyl complexes bearing different phosphine and phosphite ligands. All of the complexes were characterized with spectroscopic analysis (NMR, FT-IR, ESI-MS, UV-vis, fluorescence and XRD (for two compounds)). For biological studies, we used three types of cells – normal peripheral blood mononuclear (PBM) cells, leukemic HL-60 cells and doxorubicin-resistance HL-60 cells (HL-60/DR). We compared the results obtained with those obtained for the complex with maleimide ligand CpRu(CO)₂(η¹-N-maleimidato) 1, which we had previously reported. We observed that the complexes CpRu(CO)(PPh₃)(η¹-N-maleimidato) 2a and CpRu(CO)(P(OEt)₃)(η¹-N-maleimidato) 3a were the most cytotoxic for HL-60 cells and non-cytotoxic for normal PBM cells. However, complex 1 was more cytotoxic for HL-60 cells than complexes 2a and 3a (IC₅₀ = 6.39 μM vs. IC₅₀ = 21.48 μM and IC₅₀ = 12.25 μM, respectively). The complex CpRu(CO)(P(OPh)₃)(η¹-N-maleimidato) 3b is the most cytotoxic for HL-60/DR cells (IC₅₀ = 104.35 μM). We found the genotoxic potential of complexes 2a and 3a only in HL-60 cells. These complexes also induced apoptosis in HL-60 cells. Docking studies showed that complexes 2a and CpRu(CO)(P(Fu)₃)(η¹-N-maleimidato) 2b have a small ability to degrade DNA, but they may cause a defect in DNA damage repair mechanisms leading to cell death. This hypothesis is corroborated with the results obtained in the plasmid relaxation assay in which ruthenium complexes bearing phosphine and phosphite ligands induce DNA breaks.

The results of the X-ray structure analysis of three novel 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine cocrystals are presented. These are 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine–2,4,6-tribromophenol (1/2), C₁₂H₈N₆·2C₆H₃Br₃O, 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine–isonicotinic acid N-oxide (1/2), C₁₂H₈N₆·2C₆H₅NO₃, and 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine–4-nitrobenzenesulfonamide (1/1), C₁₂H₈N₆·C₆H₆N₂O₄S. Special attention is paid to a conformational analysis of the title tetrazine molecule in known crystal structures. Quantum chemistry methods are used to compare the energetic parameters of the investigated conformations. A structural analysis of the hydrogen and halogen bonds with acceptor aromatic tetrazine and pyrazine rings is conducted in order to elucidate factors responsible for conformational stability.

Two novel crystal structures based on melamine and salicylic acid, with either water (I) (4:3:8 molecular ratio) or ethanol (II) (2:2:1 molecular ratio), can be treated as salt solvates. In these structures, all molecular components are bound by expanded hydrogen bonding networks consisting of N-H...N, N-H...O, O-H...O, O-H…N interactions among the solvent molecules and acid-base complexes; these stabilize the crystal architecture. Special attention is paid to the N⁺-H….O^- hydrogen bonds formed between cationic melamine molecules and the ionized carboxyl group (COO^-) of anions of salicylic acid. These salt bridges exist as single contact or bifurcated double donor/acceptor hydrogen bonds which are additionally accompanied by N-H…O interactions. This present study uses quantum chemistry methods (DFT, QTAIM) to understand their nature and their energetic parameters.

In these studies, we investigated a cytotoxic and genotoxic potential of four ruthenium cyclopentadienyl complexes bearing different imidato ligands: (η⁵‐cyclopentadienyl)Ru (CO)₂(η¹‐N‐maleimidato) (1), (η⁵‐cyclopentadienyl)Ru (CO)₂‐N‐methoxysuccinimidato (2), (η⁵‐cyclopentadienyl)Ru (CO)₂‐N‐ethoxysuccinimidato (3), and (η⁵‐cyclopentadienyl)Ru (CO)₂‐N‐phthalimidato (4). We used two types of cells—normal peripheral blood mononuclear cells (PBMCs) and leukemic HL‐60 cells. We observed that complex 1 was highly cytotoxic and genotoxic, both for normal and cancer cells at concentrations from 0.5 to 250 μM. Interestingly, complex 1 was 10 times more cytotoxic to HL‐60 cells compared with PBMCs. Complexes 2–4 were cytotoxic only for HL‐60 cells at the highest used concentrations. Furthermore, we observed an increase in the viability of PBMCs after incubation with succinimide complexes 2 and 3. We also showed that complex 1 arrested cell cycle in the sub‐G1 phase and induced apoptosis. We found that different properties of studied ruthenium complexes depend significantly on the type of imide ligand bind to the ruthenium atom. The density functional theory (DFT) calculation of maleimide and succinimide revealed some significant differences of these compounds that would be related to biological activity. Our results indicate that ruthenium complex 1 should be further investigated in detail for its anticancer properties.