Key role of electrostatic interactions in bacteriorhodopsin proton transfer

The first proton transport step following photon absorption in bacteriorhodopsin is from the 13-cis retinal Schiff base to Asp85. Configurational and energetic determinants of this step are investigated here by performing quantum mechanical/molecular mechanical minimum-energy reaction-path calculations. The results suggest that retinal can pump protons when in the 13-cis, 15-anti conformation but not when 13-cis, 15-syn. Decomposition of the proton transfer energy profiles for various possible pathways reveals a conflict between the effect of the intrinsic proton affinities of the Schiff base and Asp85, which favors the neutral, product state (i.e., with Asp85 protonated), with the mainly electrostatic interaction between the protein environment with the reacting partners, which favors the ion pair reactant state (i.e., with retinal protonated). The rate-limiting proton-transfer barrier depends both on the relative orientations of the proton donor and acceptor groups and on the pathway followed by the proton; depending on these factors, the barrier may arise from breaking and forming of hydrogen bonds involving the Schiff base, Asp85, Asp212, and water w402, and from nonbonded interactions involving protein groups that respond to the charge rearrangements in the Schiff base region.     

Design, synthesis, and biochemical evaluation of 1,5,6,7-tetrahydro-6,7-dioxo-9-D-ribitylaminolumazines bearing alkyl phosphate substituents as inhibitors of lumazine synthase and riboflavin synthase

The last two steps in the biosynthesis of riboflavin, an essential metabolite that is involved in electron transport, are catalyzed by lumazine synthase and riboflavin synthase. To obtain structural probes and inhibitors of these two enzymes, two ribityllumazinediones bearing alkyl phosphate substituents were synthesized. The synthesis involved the generation of the ribityl side chain, the phosphate side chain, and the lumazine system in protected form, followed by the simultaneous removal of three different types of protecting groups. The products were designed as intermediate analogue inhibitors of lumazine synthase that would bind to its phosphate-binding site as well as its lumazine binding site. Both compounds were found to be effective inhibitors of Bacillus subtilislumazine synthase as well as Escherichia coli riboflavin synthase. Molecular modeling of the binding of one of the two compounds provided a structural explanation for how these compounds are able to effectively inhibit both enzymes. In phosphate-free buffer, the phosphate moieties of the inhibitors were found to contribute positively to their binding to Mycobacterium tuberculosis lumazine synthase, resulting in very potent inhibitors with Ki values in the low nanomolar range. The additional carbonyl in the dioxolumazine system versus the purinetrione system was found to make a positive contribution to its binding to E. coli riboflavin synthase.     

Synthesis and structural characterization of novel neutral hexacoordinate silicon(IV) complexes with SiO2N4 skeletons containing cyanato-N or thiocyanato-N ligands

A series of novel hexacoordinate silicon(IV) complexes with an SiO2N4 skeleton (compounds (OC-6-12)-3, (OC-6-12)-4, (OC-6-12)-5, (OC-6-12)-6, and (OC-6-2'2)-7) were synthesized, starting from Si(NCO)4 or Si(NCS)4. These compounds contain (i) two bidentate O,N-chelate ligands (or one tetradentate O,N,N,O-chelate ligand) derived from 4-aminopent-3-en-2-ones of the formula type Me-C(NRH)=CH-C(O)-Me (R = organyl) and (ii) two monodentate cyanato-N or thiocyanato-N ligands. Formally, the bidentate singly negatively charged O,N-chelate ligands (tetradentate 2-fold negatively charged O,N,N,O-chelate ligand) behave as ligands of the imino-enolato type. In addition, the adduct trans-8 was synthesized by reaction of Si(NCS)4 with 2 molar equiv of Me-C(Ni-PrH)=CH-C(O)-Me. This hexacoordinate silicon(IV) complex contains (i) four monodentate thiocyanato-N ligands and (ii) two neutral monodentate ligands of the iminio-enolato type. All compounds synthesized were structurally characterized by single-crystal X-ray diffraction and solid-state and solution NMR spectroscopy. To get more information about the stereochemistry of these compounds, the experimental investigations were complemented by computational studies.     

2-Hydroxyindoxyles: Preparation nouvelle et generale,proprietes et leur role lors de l'oxydation perphtalique des indoles

Oxidation with monoperphthalic acid of 2-substituted indoles led to corresponding 2-hydroxyindoxyles of which five were isolated (4c, 4d, 4f, 4g, 4h). Two more were characterized in solution by spectroscopic evidence and/or the preparation of crystalline derivatives (4a, 4c), and one showing characteristic behaviour on thin layer chromatography (4b). Longer reaction times with excess oxidant gave benzoxazones (8c, 8d, 8f, 8g). Reactions at the indole α-carbon led to bridged compounds (141, 14m).     

Absolute Rate Constants for the Addition of Benzyl (PhĊH2) and Cumyl (PhĊMe2) Radicals to Alkenes in Solution

Absolute rate constants and their temperature dependence were determined by time-resolved electron spin resonance for the addition of the radicals Ph?H₂ and Ph?Me₂ to a variety of alkenes in toluene solution. To vinyl monomers CH₂=CXY, Ph?H₂ adds at the unsubstituted C-atom with rate constants ranging from 14 M ^?1S ^?1 (ethoxyethene) to 6.7 · 10³ M ^?1S ^?1 (4-vinylpyridine) at 296 K, and the frequency factors are in the narrow range of log (A/M ^?1S ^?1) = 8.6 ± 0.3, whereas the activation energy varies with the substituents from ca. 51 kJ/mol to ca. 26 kJ/mol. The rate constants and the activation energies increase both with increasing exothermicity of the reaction and with increasing electron affinity of the alkenes and are mainly controlled by the reaction enthalpy, but are markedly influenced also by nucleophilic polar effects for electron-deficient substrates. For 1,2-disubstituted and trisubstituted alkenes, the rate constants are affected by additional steric substituent effects. To acrylate and styrenes, Ph?Me₂ adds with rate constants similar to those of Ph?H₂, and the reactivity is controlled by the same factors. A comparison with relative-rate data shows that reaction enthalpy and polar effects also dominate the copolymerization behavior of the styrene propagation radical.     

In Process Citation

The electrochemical reduction of NO(2)ClO(4) solutions at a platinum electrode in sulpholane has been studied. The results suggest the following scheme for the reduction of NO(+)(2) : 2NO(+)(2) + 2e(-) right harpoon over left harpoon 2NO(2) right harpoon over left harpoon N(2)O(4). A fast dimerization of nitrogen dioxide, which is favoured by the high donor number of sulpholane, follows the charge-transfer step. The NO(+)(2) ion is much more oxidative than the NO(+) ion in sulpholane, whereas the oxidizing power of the two species is nearly the same in nitromethane or acetonitrile solution. This result can be used to explain the role of water present at trace level.     

Rate Constants for the Addition of 2-Hydroxy-2-propyl Radicals to Alkenes in Solution studied by laser flash photolysis

Absolute rate constants for the addition of the highly nucleophilic 2-hydroxy-2-propyl radical to eight fast-reacting 1- and 1,1-disubstituted alkenes in MeOH at room temperature have been determined by laser flash photolysis. Also the absorption spectra of the 2-hydroxy-2-propyl and the benzylic and alkyl-type adduct radicals are presented. The rate constants were obtained using various methods for the analysis of the kinetic traces and support earlier findings.     

Oestron-dimethylphosphins?ureester, ein Beispiel einer neuen Derivatklasse zum empfindlichen, gas-chromatographischen Nachweis von Steroiden

Zusammenfassung Die Darstellung eines neuartigen, zum gas-chromatographischen Nachweis geeigneten Phosphorderivats von Oestron wird beschrieben. Der Oestron-dimethylphosphinsäureester läßt sich sehr empfindlich mit dem Alkaliflammenionisationsdetektor (AFID) nachweisen. Die Umsetzung von Dimethylaminodimethylphosphin mit Oestron ist unter den angegebenen Bedingungen quantitativ und sehr gut reproduzierbar. Bezugskurven mit Oestronkonzentrationen von 2–50 g Oestron im Ansatz hatten bei Nachweis mit dem FID einen Korrelationskoeffizienten von 0,999, bei Nachweis mit dem AFID von 0,998. 200 pg des Derivats konnten noch gut gemessen werden. Die Reaktionsbedingungen werden diskutiert. Auf die erfolgreiche Derivatisierung anderer Steroidhormone wird abschließend hingewiesen.

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Estrone-dimethylphosphinic ester, a new type of derivatives for the sensitive, gas chromatographic determination of steroids

The synthesis of estrone-dimethyl phosphinic ester, with good gas chromatographic properties is described. This ester is very sensitively detectable with the alkali detector. The reaction of dimethyl-amino-dimethylphosphine with estrone is quantitative and reproducible. Calibration curves with concentrations of estrone varying from 2 to 50 g per sample detected by a FID yielded a correlation coefficient of 0.999, detected by an AFID one of 0.998. The smallest amount which could be measured was 200 pg. The reaction conditions are discussed. The possibility of the derivatisation of other steroid hormones is shown.

     

Transition-Metal-Substituted Gallanes: Synthesis and Spectroscopic Studies of Highly Polar σ(M—Ga) Bonds,Structures of trans-(Ph3P)(CO)3Co—Ga[(CH2)3N(C 2H5)2]R (R = Cl,CH3) and (n5-C5H5)(CO)2Fe—GaCl2 [N(CH3)3]

The salt elimination reaction of the transition carbonyl metal-lates [L(CO)_nM](Na/K) (M = Cr, Mo, W, Mn, Re, Fe, Co, Ni; L= CO, n⁵-C₅R₅, PR₃; n= 1-4; R= alkyl, aryl) with the base-stabilized galliumhalides Cl_aGaR₃ -a(Do) (R = H, alkyl, halide; Do = THF, N(CH₃)₃, NC₇H₁₃) or Cl_aGa[(CH₂)₃N-R₂](R)₂ - _a yielded almost quantitatively the transition metal-substituted, gallanes [L(CO)_nM]_aGaR₃ - _a(Do) and [L(CO)_n-M]_aGa[(CH₂)₃NR₂](R)₂ - _a, respectively. Residual halide functionalities in these complexes were selectively replaced by various other groups. The new compounds were characterized by means of elemental analysis, ¹H-, ¹³C-, ³¹P-NMR, MS, and lR v(CO) data. The single-crystal X-ray structure analysis of trans-(Ph₃P)(CO)₃Co-Ga[(CH₂) ₃N(C₂H₅)₂](R)( 6s : R = Cl, 6t : R= CH₃) showed s̀(Co-Ga) lengths of 237.78(4) and 249.5(1) pm, respectively. A short s̀(Fe-Ga) contact of 236.18(3) pm was found for (n⁵-C₅H₅)(CO)₂Fe-Ga-Cl₂[N(CH ₃)₃] ( 5a ). Low-pressure MOCVD experiments were performed to give thin films of analytically pure CoGa alloy.