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Öğe Colloidal formulations of etoposide based on self-assembling oleyl-hyaluronan-based structures: optimization of technology and in vitro analysis(Elsevier b.v., 2025) Antonova, M.M.; Karshieva, S.Sh.; Nikitin, A.A.; Malinovskaya, Yu.A.; Ermolin, D.V.; Novikov, Alexander S.; Skorb, E.V.; Beigulenko, D.V.; Kovshova, T.S.; Kalacheva, E.A.; Filin, A.A.; Gelperina, S.E.The ability of the conjugate of hyaluronic acid and oleic acid (oleyl hyaluronan — HA-C18:1) to form self-assembling micellar structures was utilized to enhance the water solubility of the anticancer drug etoposide (ETP) and its prodrug, 4-O′-benzyloxycarbonyl derivative (ETP-Cbz). Using density functional theory (DFT), it was established that the ETP-Cbz associate with HA-C18:1 had greater thermodynamic stability compared to the ETP associate, which was confirmed experimentally. The micelles loaded with ETP-Cbz were smaller (268 nm compared to 407 nm), more stable (with the critical micelle concentration (CMC) decreasing from 0.07 to 0.025 mg/mL), and had the higher drug loading efficiency (82 %) as compared to HA-C18:1/ETP micelles. In vitro experiments showed that both micellar formulations exhibited low hemolytic activity and delayed drug release profiles during the first hours. In vitro cytotoxicity against MCF-7 and MDA-MB-231 cell lines showed the dose-dependent decrease in cell viability whereas the toxic effect against normal human dermal fibroblasts (NHDF) was significantly lower and exceeded the concentration of HA-C18:1 in the micellar formulations. Confocal microscopy was used to confirm the active uptake of micellar formulations by MDA-MB-231 cells. These findings, therefore, suggest that HA-C18:1 may be a promising solubilizing agent for etoposide and its prodrug.Öğe Different topology of mixed valence CoIICoIII complexes with SCN anions and hydrazone–pyridine-based ligands(Springer, 2024) Mahmoudi, Ghodrat; Novikov, Alexander S.; Balić, Tomislav; Zangrando, Ennio; White, Jonathan M.; Eftekhari-Sis, BagherTwo novel mixed valence CoIICoIII complexes [Co4II(SCN)12(EtOH)2Co4III(L1)8] (1) and [CoII(SCN)2Co2III(L2)4]n (2) (HL1 = N’-(1-(pyridin-2-yl)ethylidene)nicotinohydrazide and HL2 = N’-(phenyl(pyridin-2-yl)methylene)isonicotinohydrazide) have been synthesized and structurally characterized by the single crystal X-ray crystallography. In both cases, the deprotonated ligands HL1 and HL2 behave as chelating species toward CoIII, further connecting CoII fragments through the nicotine pyridine donors. A different topology is observed in the solid state of these complexes, complex 1 being an octanuclear cyclic species, while 2 is a 1D coordination polymer. The DFT calculations followed by the topological analysis of the electron density distribution have shown the existence of interesting non-covalent S···π-system interactions in 1. The CSD database search for similar supramolecular motif involving NCS anion has shown that the number and strength of S···π interactions depend both on acidity of metal cation and number aromatic systems in the molecular structure of ligand. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.Öğe Synthesis and characterization of a series of lead complexes with (pyrazinyl)benzohydrazone ligand and theoretical studies of their supramolecular dimerization in solid state(Elsevier b.v., 2025) Mahmoudi, Ghodrat; Garcia-Santos, Isabel; Novikov, Alexander S.; Kornilov, Dmitry A.; Fernández-Vazquez, Roi; Castiñeiras, Alfonso; Zangrando, EnnioWe have synthesized a series of lead complexes with pyrazinyl-4-methylbenzoylhydrazone (HPyz) and different anions as ancillary ligands, namely [Pb(HPyz)Cl2] (1), [Pb(Pyz)(NO2)] (2), [Pb(Pyz)(NO3)(H2O)] (3), [Pb(Pyz) (NO2)0.5(NO3)0.5(H2O)] (4), and [Pb(Pyz)(SCN)(H2O)] (5). These complexes have been characterized by 1H NMR, IR, and X-ray diffraction techniques. All the complexes show a comparable coordination mode of the organic ligand while the supramolecular crystal structure is addressed by the anions and coordinated water molecules when present. In fact, the solid state is characterized by it-stacking interactions between pyrazine and phenyl rings. In particular, inspection of X-ray data reveals dimerization of centrosymmetric related species of these lead complexes via various noncovalent interactions. To assess the nature of these intermolecular interactions, the Hirshfeld surface analysis and DFT calculations, followed by topological analysis of the electron density distribution within the QTAIM approach and NCI analysis, have been carried out for the model structures based on the experimental X-ray diffraction analysis data. The Hirshfeld surface analysis for the X-ray structures reveals that in all cases crystal packing is determined primarily by intermolecular contacts involving hydrogen atoms. The QTAIM analysis of model structures demonstrates the presence of bond critical points for various intermolecular interactions responsible for the supramolecular dimerization of the studied lead complexes in solid state.