Sinteza, NMR i DFT proračunavanja i ispitivanje antimikrobne aktivnosti Zn(II) kompleksa sa N-benziloksikarbonil-S-alaninom

In this study, the first complexes of Zn(II) with the N-benzyloxycarbonyl-S-alaninato ligand (N-Boc-S-ala) were synthesized. The new complexes were characterized by elemental analysis, conductometric measurements, IR. (1)H-NMR, (13)C-NMR and 2D-NMR spectroscopy. On the basis of the experimental data, tetrahedral geometry of the Zn(II) complexes was proposed. A very good agreement between the NMR and DFT calculated data was obtained. Investigation of antimicrobial activity of the newly synthesized complexes was also performed. It was established that [Zn(N-Boc-S-ala)(2)] was selective and acts only on Candida aibicans.U ovom radu su sintetizovani prvi kompleksi Zn(II) sa N-benziloksikarbonil-S-alaninato ligandom (N-Boc-S-ala). Kompleksi su okarakterisani elementalnom analizom, konduktometrijskim merenjem, IR, 1H-NMR, 13C-NMR i 2D-NMR spektroskopijom. Tetraedarska geometrija Zn(II) kompleksa pretpostavljena je na osnovu eksperimentalnih podataka. Dobijeno je veoma dobro slaganje između NMR i DFT podataka. Ispitivana je antimikrobna aktivnost novosintetizovanih kompleksa. Ustanovljeno je da je [Zn(N-Boc-S-ala)2] kompleks selektivan i da deluje samo na gljivu Candida albicans

18 O-assisted dynamic metabolomics for individualized diagnostics and treatment of human diseases

Technological innovations and translation of basic discoveries to clinical practice drive advances in medicine. Today’s innovative technologies enable comprehensive screening of the genome, transcriptome, proteome, and metabolome. The detailed knowledge, converged in the integrated “omics” (genomics, transcriptomics, proteomics, and metabolomics), holds an immense potential for understanding mechanism of diseases, facilitating their early diagnostics, selecting personalized therapeutic strategies, and assessing their effectiveness. Metabolomics is the newest “omics” approach aimed to analyze large metabolite pools. The next generation of metabolomic screening requires technologies for high throughput and robust monitoring of metabolite levels and their fluxes. In this regard, stable isotope 18O-based metabolite tagging technology expands quantitative measurements of metabolite levels and turnover rates to all metabolites that include water as a reactant, most notably phosphometabolites. The obtained profiles and turnover rates are sensitive indicators of energy and metabolic imbalances like the ones created by genetic deficiencies, myocardial ischemia, heart failure, neurodegenerative disorders, etc. Here we describe and discuss briefly the potential use of dynamic phosphometabolomic platform for disease diagnostics currently under development at Mayo Clinic

18 O-assisted dynamic metabolomics for individualized diagnostics and treatment of human diseases

Technological innovations and translation of basic discoveries to clinical practice drive advances in medicine. Today’s innovative technologies enable comprehensive screening of the genome, transcriptome, proteome, and metabolome. The detailed knowledge, converged in the integrated “omics” (genomics, transcriptomics, proteomics, and metabolomics), holds an immense potential for understanding mechanism of diseases, facilitating their early diagnostics, selecting personalized therapeutic strategies, and assessing their effectiveness. Metabolomics is the newest “omics” approach aimed to analyze large metabolite pools. The next generation of metabolomic screening requires technologies for high throughput and robust monitoring of metabolite levels and their fluxes. In this regard, stable isotope 18O-based metabolite tagging technology expands quantitative measurements of metabolite levels and turnover rates to all metabolites that include water as a reactant, most notably phosphometabolites. The obtained profiles and turnover rates are sensitive indicators of energy and metabolic imbalances like the ones created by genetic deficiencies, myocardial ischemia, heart failure, neurodegenerative disorders, etc. Here we describe and discuss briefly the potential use of dynamic phosphometabolomic platform for disease diagnostics currently under development at Mayo Clinic

Electron delocalization mediates the metal-dependent capacity for CH/pi interactions of acetylacetonato chelates

CH/pi interactions between the coordinated acetylacetonato ligand and phenyl rings were analyzed in the crystal structures from the Cambridge Structural Database and by quantum chemical calculations. The acetylacetonato ligand may engage in two types of interactions: it can be hydrogen atom donor or acceptor. The analysis of crystal structures and calculations show that interactions with the acetylacetonato ligand acting as hydrogen atom donor depend on the metal in an acetylacetonato chelate ring; the chelate rings with soft metals make stronger interactions. The same trend was not observed in the interactions where the acetylacetonato chelate ring acts as the hydrogen atom acceptor

Synthesis and characterization of novel Cd(II), Zn(II) and Ni(II) complexes with 2-quinolinecarboxaldehyde selenosemicarbazone. Crystal structure of bis(2-quinolinecarboxaldehyde selenosemicarbazonato)nickel(II)

New complexes of Cd(II), Zn(II) and Ni(II) with 2-quinolinecarboxaldehyde selenosernicarbazone (Hqasesc) were synthesized and structurally characterized. The structure of the ligand, Cd(II) and Zn(II) complexes was determined by NMR and IR spectroscopy, elemental microanalysis and molar conductivity measurements. Both complexes occur in solution in two forms, the major tetrahedral and minor octahedral. In the major Cd(II) complex one qasesc(-) ligand is coordinated as a tridentate, the fourth coordination site being occupied by acetate, while in the major Zn(II) complex two qasesc- ligands are coordinated as bidentates. In both minor complexes two qasesc- ligands are coordinated as tridentates forming the octahedral geometry around the central metal ion. The only paramagnetic complex in the series is Ni(II) complex for which X-ray structure analysis was performed. The complex has the angularly distorted octahedral geometry with two qasesc- ligands coordinated as tridentates, in a similar way as in the minor complexes of Cd(11) and Zn(11). (c) 2007 Elsevier Ltd. All rights reserved

Saturation Transfer Difference Nuclear Magnetic Resonance Spectroscopy As a Method for Screening Proteins for Anesthetic Binding

ABSTRACT The effects of anesthetics on cellular function may result from direct interactions between anesthetic molecules and proteins. These interactions have a low affinity and are difficult to characterize. To identify proteins that bind anesthetics, we used nuclear magnetic resonance saturation transfer difference (STD) spectroscopy. The method is based on the nuclear Overhauser effect between bound anesthetic protons and all protein protons. To establish STD as a method for testing anesthetic binding to proteins, we conducted measurements on a series of protein/anesthetic solutions studied before by other methods

Synthesis and characterization of Zn(II) and Cd(II) complexes with 2,6-diacetylpyridine-bis(selenosemicarbazone). Crystal structure of a Ni(II) complex with a modified 2.6-diacetylpyridine-bis(selenosemicarbazone)

A novel ligand 2,6-diacetylpyridine-bis(selenosemicarbazone) was synthesized and coordinated with Zn(II), Cd(II) and Ni(II). With Zn(II) and Cd(II), the bideprotonated ligand was coordinated as a quinquedentate in trigonal bipyramidal geometry. With Ni(II) during coordination the ligand was modified by elimination of hydrogen selenide and the product was coordinated as a quadridentate forming a square planar complex, the structure of which was determined by X-ray analysis. (C) 2006 Elsevier B.V. All rights reserved

Dynamic Phosphometabolomic Profiling of Human Tissues and Transgenic Models By O-18-Assisted P-31 Nmr and Mass Spectrometry

Next-generation screening of disease-related metabolomic phenotypes requires monitoring of both metabolite levels and turnover rates. Stable isotope O-18-assisted P-31 nuclear magnetic resonance (NMR) and mass spectrometry uniquely allows simultaneous measurement of phosphometabolite levels and turnover rates in tissue and blood samples. The O-18 labeling procedure is based on the incorporation of one O-18 into Pi from [O-18]H2O with each act of ATP hydrolysis and the distribution of O-18-labeled phosphoryls among phosphate-carrying molecules. This enables simultaneous recording of ATP synthesis and utilization, phosphotransfer fluxes through adenylate kinase, creatine kinase, and glycolytic pathways, as well as mitochondrial substrate shuttle, urea and Krebs cycle activity, glycogen turnover, and intracellular energetic communication. Application of expanded O-18-labeling procedures has revealed significant differences in the dynamics of G-6-P[O-18] (glycolysis), G-3-P[O-18] (substrate shuttle), and G-1-P[O-18] (glycogenolysis) between human and rat atrial myocardium. In human atria, the turnover of G-3-P[O-18], which defects are associated with the sudden death syndrome, was significantly higher indicating a greater importance of substrate shuttling to mitochondria. Phosphometabolomic profiling of transgenic hearts deficient in adenylate kinase (AK1-/-), which altered levels and mutations are associated to human diseases, revealed a stress-induced shift in metabolomic profile with increased CrP[O-18] and decreased G-1-P[O-18] metabolic dynamics. The metabolomic profile of creatine kinase M-CK/ScCKmit-/--deficient hearts is characterized by a higher G-6-[O-18]P turnover rate, G-6-P levels, glycolytic capacity, gamma/beta-phosphoryl of GTP[O-18] turnover, as well as beta-[O-18]ATP and beta-[O-18]ADP turnover, indicating altered glycolytic, guanine nucleotide, and adenylate kinase metabolic flux. Thus, O-18-assisted gas chromatography-mass spectrometry and P-31 NMR provide a suitable platform for dynamic phosphometabolomic profiling of the cellular energetic system enabling prediction and diagnosis of metabolic diseases states.Wo