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Protein molecules, although big and complicated structures, arrange into ordered crystal formations, but at specific only conditions, related to pH, additives and temperature. Truly, their crystallization is still more art than science and conditions relating their behavior to the known rules of crystal growth and dissolution are under investigation. This study is devoted to dissolution and more precise - the influence of undersaturation on the habitus of the dissolving tetragonal lysozyme crystals. Experiments described reveal that the morphologies of the dissolving crystals at low and high levels of undersaturations go through wholly different habitus. Rounding and diminishing the crystal happens at low undersaturation. Dissolution at higher undersaturation revealed development of ribbed crystal habitus, never noticed for dissolving low molecular weight crystals. Its formation could be explained with specific distribution of energetic places on the crystal surface. Existence of such energetic places is conditioned by inner channels passing through the crystal. A model relating these channels distribution and shapes observed during dissolving is presented.

The food industry is interested in replacing artificial sweeteners with natural sugars that possess zero calories and carbohydrates and do not cause spikes in blood sugar levels. The steviosides leaves, synthesized at

Complex neurological disorders, including Alzheimer's disease, are one of the major therapeutic areas to which multitarget drug discovery strategies have been applied in the last twenty years. Due to the complex multifactorial etiopathogenesis of Alzheimer's disease, it has been proposed that to be successful the pharmaceutical agents should act on multiple targets in order to restore the complex disease network and to provide disease modifying effects. Here we report on the synthesis and the anticholinergic activity profiles of seven multitarget anti-Alzheimer compounds designed by combining galantamine, a well-known acetylcholinesterase inhibitor, with different peptide fragments endowed with inhibitory activity against BACE-1. A complementary approach based on molecular docking simulations of the galantamine-peptide derivatives in the active sites of acetylcholinesterase and of the related butyrylcholinesterase, as well as on inhibition kinetics, by global fitting of the reaction progress curves, allowed to gain insights into the enzyme-inhibitor mechanism of interaction. The resulting structure-activity relationships pave the way towards the design of more effective pharmacodynamic/pharmacokinetic multitarget inhibitors.

Two paramagnetic PdIII complexes of hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp), namely a dinuclear one [PdIII2(Hp-3H)Cl3(H2O)5]&middot, 2PdCl2, Pd1 and a mononuclear metalloporphyrin type [PdIII(Hp-2H)Cl(H2O)]&middot, H2O, Pd2 have been synthesized reproducibly and isolated as neutral compounds at different reaction conditions. Their structure and solution stability have been assayed by UV/Vis and EPR spectroscopy. The compounds researched have shown in vitro cell growth inhibitory effects at micromolar concentration against a panel of human tumor cell lines. A DNA fragmentation test in the HL-60 cell line has indicated that Pd1 causes comparable proapoptotic effects with regard to cisplatin but at substantially higher concentrations. Pd1 and cisplatin form intra-strand guanine bis-adducts as the palladium complex is less capable of forming DNA adducts. This demonstrates its cisplatin-dissimilar pharmacological profile. The test for efficient removal of DNA-adducts by the NER synthesis after modification of pBS plasmids with either cisplatin or Pd1 has manifested that the lesions induced by cisplatin are far better recognized and repaired compared those of Pd1. The study on the recognition and binding of the HMGB-1 protein to cisplatin or Pd1 modified DNA probes have shown that HMG proteins are less involved in the palladium agent cytotoxicity.

Three novel stable Pt(III) complexes with distorted octahedral structure and (dz2)1 ground state have been obtained in the course of Pt(II)-hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp) interaction in alkaline aqueous medium and aerobic conditions. A redox interaction also takes place together with the complexation process leading to the formation of Pt(III) species and organic radicals. The processes in the reaction system and the structure of the complexes formed cis-[Pt(III)(NH3)2(Hp−3H)(H2O)2]⋅H2O1, [Pt(III)(Hp−3H)(H2O)2]⋅H2O2, and [Pt((O,O)Hp−2H)Cl(H2O)3] 3, were studied by UV-Vis, IR, EPR and XPS spectra, thermal (TGS, DSC), potentiometric and magnetic methods. The newly synthesized complexes show promising cytotoxic activity comparable with that of cis-platin in in vitro tests against a panel of human leukemia cell lines. The observed cytotoxicity of the complex 2 against SKW-3 cells (KE-37 derivative) is due to induction of cell death through apoptosis.

Two coordination compounds of Pd(III) with hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp), dinuclear [Pd(III)2(Hp-3H)Cl3(H2O)5]·2PdCl2, 1 and mononuclear [Pd(III)(Hp-2H)Cl(H2O)]·H2O, 2 were obtained and structurally characterized in solid state and solution using spectroscopic, thermal and magnetic methods. In the dinuclear complex, 1 one of the Pd(III) ions is coordinated to the deprotanated COO(-) groups from the side chains of the porphyrin ligand and the second Pd(III) ion - to two adjacent pyrrole N-atoms on the top of the porphyrin ring and a Pd(III)-Hp-Pd(III) system was formed. The Pd(III) ion in the mononuclear complex, 2 is incorporated in the porphyrin core. The Pd(III) centers in both complexes have a distorted octahedral coordination filled with additional donor species such as Cl(-) and H2O. The studied compounds showed in vitro cell growth inhibitory effects at micromolar concentration against a panel of human tumor cell lines. A DNA fragmentation assay indicated that the growth inhibitory effects are at least partly mediated by induction of apoptosis.

Three stable mononuclear hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp) complexes of Pt(III), namely cis-[ Pt(III)(NH(3))(2)(Hp(-3H))(H(2)O)(2)].H(2)O 1, [Pt(III)(Hp(-3H))(H(2)O)(2)].H(2)O 2 and [Pt(III)((O,O)Hp(-2H))Cl(H(2)O)(3)] 3 with distorted octahedral structure and (d(z)2)(1) ground state have been tested in vitro for antineoplastic activity in a panel of tumor cell lines. The novel platinum(III) complexes showed cytotoxic activity in a concentration-dependent manner with IC(50) values comparable to those of referent cytotoxic agent cisplatin together with lower cytotoxicity against renal cells. Further detailed evaluation of the active analogue 2 and the less active complex 3 showed that their potency greatly correlates with the ability to induce apoptosis and to bind DNA. Despite the structural dissimilarities between complex 2 and cisplatin, their DNA-adducts were equally effectively recognized and repaired by the nucleotide excision repair system. Complex 2 showed quite superior ability to accumulate in K-562 cells relative to cisplatin.