<i>N,N</i>-bis-(dimethylfluorosilylmethyl)amides of <i>N</i>-organosulfonylproline and sarcosine: synthesis, structure, stereodynamic behaviour and <i>in silico</i> studies

(O→Si)-Chelate difluorides R3R2NCH(R1)C(O)N(CH2SiMe2F)2 (9a–c, R1R2 = (CH2)3, R3 = Ms (a), Ts (b); R1 = H, R2 = Me, R3 = Ms (c)), containing one penta- and one tetracoordinate silicon atoms were synthesized by silylmethylation of amides R3R2NCH(R1)C(O)NH2, subsequent hydrolysis of unstable intermediates R3R2NCH(R1)C(O)N(CH2SiMe2Cl)2 (7a–c) into 4-acyl-2,6-disilamorpholines R3R2NCH(R1)C(O)N(CH2SiMe2O)2 (8a–c) and the reaction of the latter compounds with BF3·Et2O. The structures of disilamorpholines 8a,c and difluoride 9a were confirmed by an X-ray diffraction study. According to the IR and NMR data, the O→Si coordination in solutions of these compounds was weaker than that in the solid state due to effective solvation of the Si–F bond. A permutational isomerisation involving an exchange of equatorial Me groups at the pentacoordinate Si atom in complexes 9a–c was detected, and its activational parameters were determined by 1H DNMR. In silico estimation of possible pharmacological effects and acute rat toxicity by PASS Online and GUSAR Online services showed a potential for their further pharmacological study

ОБНАРУЖЕНИЕ ГИДРОПЕРОКСИДОВ В РАСТВОРАХ ФОТООКИСЛЕННОГО ПСОРАЛЕНА

Photooxidized psoralen solutions possess a variety of biological effects, which implementation mechanism may presumably involve hydroperoxides. Here, the hydroperoxide content in photooxidized psoralen solutions was assessed using photometric FOX assay (from Ferrous Oxidation + Xylenol Orange). FOX reagent with 10× content of Xylenol Orange, modified for quantitative analysis of up to 50 μM of hydroperoxides in aqueous phase was used in experiments. During photooxidation of 0.1 mM psoralen in phosphate buffer solution, hydroperoxide production increases with dose of UVA irradiation (~2.5 μM eq. of H2O2 for dose of 252 kJ/m2 and ~11 μM eq. of H2O2 for dose of 1512 kJ/m2) and reaches ~16.5 μM eq. of H2O2 at the highest dose investigated (3024 kJ/m2). A comparison of kinetics of psoralen photolysis and hydroperoxide generation allows us to suggest that generation of hydroperoxide results from the secondary photochemical processes involving psoralen photoproducts, presumably from photoinduced autooxidation of aldehydic photoproducts of psoralen.Растворы фотоокисленного псоралена обладают целым рядом биологических эффектов, механизм реализации которых предполагает участие в них гидропероксидов. В настоящей работе содержание гидропероксидов в растворах фотоокисленного псоралена оценивали фотометрически методом FOX-анализа (от англ. Ferrous Oxidation + Xylenol Orange). В экспериментах использовали модифицированный FOX-реагент, с 10-кратным содержанием ксиленолового оранжевого, позволяющий количественно обнаруживать в водной фазе до 50 мкМ гидропероксидов. В процессе фотоокисления 0.1 мМ раствора псоралена в фосфатном буферном растворе продукция гидропероксидов растет с увеличением дозы УФ-А-облучения (~2.5 мкМ экв. H2O2 для дозы 252 кДж/м2 и ~11 мкМ экв. H2O2 для дозы 1512 кДж/м2) и достигает ~16.5 мкМ экв. H2O2 в случае максимальной исследованной дозы облучения (3024 кДж/м2). Сравнение кинетики фотолиза псоралена и формирования гидропероксидов позволяет сделать вывод, что генерация гидропероксидов является результатом вторичных фотохимических процессов с участием фотопродуктов псоралена, предположительно, фотоиндуцированного автоокисления фотопродуктов псоралена альдегидной природы

Plants with genetically encoded autoluminescence

Autoluminescent plants engineered to express a bacterial bioluminescence gene cluster in plastids have not been widely adopted because of low light output. We engineered tobacco plants with a fungal bioluminescence system that converts caffeic acid (present in all plants) into luciferin and report self-sustained luminescence that is visible to the naked eye. Our findings could underpin development of a suite of imaging tools for plants

Reaction of Picolinamides with Ketones Producing a New Type of Heterocyclic Salts with an Imidazolidin-4-One Ring

Reactions of picolinamides with 1,3-propanesultone in methanol followed by the treatment with ketones led to a series of previously unknown chemical transformations, yielding first pyridinium salts (2a–f), with a protonated endocyclic nitrogen atom, and then heterocyclic salts (3a–j) containing an imidazolidin-4-one ring. The structures of intermediate and final products were determined by IR and 1H, 13C NMR spectroscopy, and X-ray study. The effects of the ketone and alcohol structures on the product yield were studied by quantum-chemical calculations. The stability of salts 3a–j towards hydrolysis and alcoholysis makes them excellent candidates for the search for new types of biologically active compounds

DETECTION OF HYDROPEROXIDES IN SOLUTIONS OF PHOTOOXIDIZED PSORALEN

Photooxidized psoralen solutions possess a variety of biological effects, which implementation mechanism may presumably involve hydroperoxides. Here, the hydroperoxide content in photooxidized psoralen solutions was assessed using photometric FOX assay (from Ferrous Oxidation + Xylenol Orange). FOX reagent with 10× content of Xylenol Orange, modified for quantitative analysis of up to 50 μM of hydroperoxides in aqueous phase was used in experiments. During photooxidation of 0.1 mM psoralen in phosphate buffer solution, hydroperoxide production increases with dose of UVA irradiation (~2.5 μM eq. of H2O2 for dose of 252 kJ/m2 and ~11 μM eq. of H2O2 for dose of 1512 kJ/m2) and reaches ~16.5 μM eq. of H2O2 at the highest dose investigated (3024 kJ/m2). A comparison of kinetics of psoralen photolysis and hydroperoxide generation allows us to suggest that generation of hydroperoxide results from the secondary photochemical processes involving psoralen photoproducts, presumably from photoinduced autooxidation of aldehydic photoproducts of psoralen

Proton catalysis of nucleophilic substitution at pentacoordinate silicon

Addition of acid to the pentacoordinate fluorosilane 8, leads to enhanced exchange of fluorine and loss of diastereotopicity of the silicon methyl groups. A DNMR study of the H-1-NMR spectra suggests a dissociative mechanism involving protonation of the fluorine leaving group. Variable temperature studies suggest that at lower temperatures the tetracoordinate form is favoured. (C) 2002 Elsevier Science B.V. All rights reserved

Twice as Nice: The Duff Formylation of Umbelliferone Revised

More efficient and preferably more convenient and greener synthetic solutions in coumarin scaffold functionalization are in steady demand. The Duff ortho-formylation of unsubstituted umbelliferone was revised in this study. The reaction conditions were optimized based upon data from the literature analysis and resulted in unexpectedly rapid ortho-formylation of umbelliferone, yielding a mixture of ortho-formyl position isomers. Thorough studies on the separation of ortho-formylated umbelliferones using chromatographic and recrystallization methods as well as the evaluation of their solubility in common organic solvents led to complete resolution of 8-formyl- and 6-formylumbelliferones. The precise protocol for simultaneous preparation, extraction, and purification of 8-formyl- and 6-formylumbelliferones is provided, and the prospective studies of biological and pharmacological activities of these compounds are synopsized

Stereochemical rearrangements of dibromides of hexacoordinated germanium containing amidomethyl and lactamomethyl chelate ligands

For the first time a slow (on the NMR time scale) dynamic exchange between two diastereomers of hexacoordinated dibromogermanes containing two amidomethyl and lactamomethyl C,O-chelate ligands has been observed at room temperature in solution. The influence of temperature and solvent on the ratio of diastereomers was studied. At higher temperatures only one set of signals of the products were detected in the NMR spectra. Based on the dynamic NMR and quantum-chemical calculations (ab initio FR 3-21G), as well as on the structures determined for these compounds in the solid state, a cis-configuration of monodentate ligands was proposed for one of the diastereomers and an all-trans-configuration for the other. At low temperatures interconversion of enantiomers in the cis-diastereomer was observed. In the case of bis[(N-methylacetamido)methyl]dibromogermane the activation and thermodynamic parameters of enantiomerization (DeltaG(298)(#) 12.0+/-0.1 kcal mol(-1), DeltaH(#) 10.7+/-0.3 kcal mol(-1), DeltaS(#) -4.6+/-2.5 cal mol(-1) K-1) and diastereomeric exchange OcCtBrcreversible arrowOtCtBrt (DeltaG(298)(#), 15.0+/-0.1 kcal mol(-1); DeltaH(#) 0.1+/-0.8 kcal mol(-1); DeltaS(#) -50.0+/-5.8 cal mol(-1) K-1; DeltaG(298)degrees -0.2+/-0.1 kcal mol(-1); DeltaHdegrees -0.8+/-0.8 kcal mol(-1); DeltaSdegrees -2.6+/-1.0 cal mol(-1) K-1) were determined. (C) 2003 Published by Elsevier Science B.V

Modelling nucleophilic substitution at silicon using solution 19F NMR chemical shift, 1JSi‑F and 2JC‑F coupling constant data of pentacoordinate silicon compounds. Correlation with other magnetic nuclei and X-ray structures,

Solution 1JSi---F and 2JC---F NMR coupling constant and 19F-NMR chemical shift data have been analysed in a series of pentacoordinate silyl monofluoride complexes used to model nucleophilic substitution at silicon. Patterns in the data reveal strong correlations between both coupling constants and 19F-NMR chemical shifts and the degree of substitution displayed by each. Excellent correlation is obtained between the new data and our previous 13C- and 29Si-NMR studies to further confirm the validity of the NMR technique for structural correlation in solution. By pooling the X-ray crystal structures of a large number of compounds of this class from both our own results and the literature we are able to provide a possible explanation for some of the trends in the NMR data we observe in solution

Structures and stereochemical non-rigidity of Si-substituted N-(dimethylsilylmethyl)- and N-(methylphenylsilylmethyl)amides and -lactams

Eleven new silicon-substituted N-(dimethylsilylmethyl)- and N-(methylphenylsilylmethyl)amides and -lactams bearing a chiral carbon in the amide or lactam fragment, and containing the OSiC3X (X = Hal, OTf) coordination fragment have been synthesized and their structures determined in solution by spectroscopic means. These structures are consistent with the hypervalency model. Quantum chemical calculations adequately reflect correlations between the type of monodentate ligand X and the geometric parameters of the N–C�O–Si�X fragments. The activation parameters for enantiomerization and diastereomerization in these new compounds and the other related compounds were determined by the dynamic NMR (DNMR) method using full line-shape analysis. The free activation energy values in the absence of external nucleophiles vary from 9 to 27 kcal mol?1. The entropies of activation (?S#) are negative (?20 to ?50 cal mol?1 K?1) in all cases except for the chloride derivatives of 4-phenyl-2-pyrrolidone and 4-oxazolidinone that have weaker intramolecular O ? Si coordination. Irregular mechanisms of permutational isomerization were proposed on the basis of the DNMR data and the results of quantum-chemical calculations carried out by ab initio (HF) and DFT (PBE, B3PW91, 6-311++G(d,p)). Depending on the coordination environment at silicon, the mechanisms proposed involve either the dissociation of the Si–X bond followed by the Berry pseudorotation or similar in the intermediate or the cleavage of intramolecular O–Si bond with subsequent inversion at the silicon atom. The apparently simple pseudorotation mechanism involving only the pentacoordinate structures 1–21 does not appear to be favoured in any of the examples studied