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Cooperative Effects (cooperative + effects)
Selected AbstractsCooperative Effects on Radical Recombination in CYP3A4-Catalyzed Oxidation of the Radical Clock ,-ThujoneCHEMBIOCHEM, Issue 4 2009Yongying Jiang Dr. Abstract Tick tock: The timing of the ,-thujone radical clock (see scheme) can be specifically altered by an allosteric effector. Progesterone, a well-documented CYP3A4 allosteric effector, was found to increase the yield of the unrearranged, C4-derived product of ,-thujone oxidation at the expense of the combined yields of all the rearranged C4-oxidized metabolites. The results demonstrate that the apparent radical recombination rate in the CYP3A4 hydroxylation of ,-thujone is accelerated by the progesterone hetereotropic cooperativity. [source] Do Trinuclear Triplesalen Complexes Exhibit Cooperative Effects?CHEMISTRY - A EUROPEAN JOURNAL, Issue 33 2010Characterization, Enantioselective Catalytic Sulfoxidation by Chiral Trinuclear FeIII Triplesalen Complexes, Synthesis Abstract The chiral triplesalen ligand H6chand provides three chiral salen ligand compartments in a meta -phenylene arrangement by a phloroglucinol backbone. The two diastereomeric versions H6chandRR and H6chandrac have been used to synthesize the enantiomerically pure chiral complex [(FeCl)3(chandRR)] (3RR) and the racemic complex [(FeCl)3(chandrac)] (3rac). The molecular structure of the free ligand H6chandrac exhibits at the terminal donor sides the O-protonated phenol,imine tautomer and at the central donor sides the N-protonated keto,enamine tautomer. The trinuclear complexes are comprised of five-coordinate square-pyramidal FeIII ions with a chloride at the axial positions. The crystal structure of 3rac exhibits collinear chiral channels of ,11,Å in diameter making up 33.6,% of the volume of the crystals, whereas the crystal structure of 3RR exhibits voids of 560,Å3. Mössbauer spectroscopy demonstrates the presence of FeIII high-spin ions. UV/Vis spectroscopy is in accordance with a large delocalized system in the central backbone evidenced by strong low-energy shifts of the imine ,,,* transitions relative to that of the terminal units. Magnetic measurements reveal weak intramolecular exchange interactions but strong magnetic anisotropies of the FeIII ions. Complexes 3rac and 3RR are good catalysts for the sulfoxidation of sulfides providing very good yields and high selectivities with 3RR being enantioselective. A comparison of 3RR and [FeCl(salen,)] provides higher yields and selectivities but lower enantiomeric excess values (ee values) for 3RR relative to [FeCl(salen,)]. The low ee values of 3RR appeared to be connected to a strong ligand folding in 3RR, opening access to the catalytically active high-valent Fe,O species. The higher selectivity is assigned to a cooperative stabilization of the catalytically active high-valent Fe,O species through the phloroglucinol backbone in the trinuclear complexes. [source] Cooperative effects of bcl-2 and AAV-mediated expression of CNTF on retinal ganglion cell survival and axonal regeneration in adult transgenic miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006Simone G. Leaver Abstract We used a gene therapy approach in transgenic mice to assess the cooperative effects of combining anti-apoptotic and growth-promoting stimuli on adult retinal ganglion cell (RGC) survival and axonal regeneration following intraorbital optic nerve injury. Bi- cistronic adeno-associated viral vectors encoding a secretable form of ciliary neurotrophic factor and green fluorescent protein (AAV-CNTF-GFP) were injected into eyes of mice that had been engineered to over-express the anti-apoptotic protein bcl-2. For comparison this vector was also injected into wildtype (wt) mice, and both mouse strains were injected with control AAV encoding GFP. Five weeks after optic nerve injury we confirmed that bcl-2 over-expression by itself promoted the survival of axotomized RGCs, but in contrast to previous reports we also saw regeneration of some mature RGC axons beyond the optic nerve crush. AAV-mediated expression of CNTF in adult retinas significantly increased the survival and axonal regeneration of RGCs following axotomy in wt and bcl-2 transgenic mice; however, the effects were greatest in the transgenic strain. Compared with AAV-GFP-injected bcl-2 mice, RGC viability was increased by about 50% (mean, 36 738 RGCs per retina), and over 1000 axons per optic nerve regenerated 1,1.5 mm beyond the crush. These findings exemplify the importance of using a multifactorial therapeutic approach that enhances both neuroprotection and regeneration after central nervous system injury. [source] Ditopic Cyclodextrin-Based Receptors: New Perspectives in Aqueous Organometallic CatalysisADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 9 2010Natacha Six Abstract The mass transfer properties of mono- and ditopic ,-cyclodextrin-based receptors have been evaluated in a biphasic palladium-catalyzed Tsuji,Trost reaction and compared to one of the best mass-transfer promoters, namely the randomly methylated ,-cyclodextrin. While monotopic receptors appeared to be poor mass-transfer promoters of long alkyl chain allyl carbonates or urethanes, cooperative effects have been evidenced with ditopic cyclodextrin-based receptors, opening new perspectives in aqueous organometallic catalysis. [source] A comprehensive theoretical study on the hydrolysis of carbonyl sulfide in the neutral waterJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 3 2008Chao Deng Abstract The detailed hydration mechanism of carbonyl sulfide (COS) in the presence of up to five water molecules has been investigated at the level of HF and MP2 with the basis set of 6-311++G(d, p). The nucleophilic addition of water molecule occurs in a concerted way across the CS bond of COS rather than across the CO bond. This preferential reaction mechanism could be rationalized in terms of Fukui functions for the both nucleophilic and electrophilic attacks. The activation barriers, ,H, for the rate-determining steps of one up to five-water hydrolyses of COS across the CS bond are 199.4, 144.4, 123.0, 115.5, and 107.9 kJ/mol in the gas phase, respectively. The most favorable hydrolysis path of COS involves a sort of eight-membered ring transition structure and other two water molecules near to the nonreactive oxygen atom but not involved in the proton transfer, suggesting that the hydrolysis of COS can be significantly mediated by the water molecule(s) and the cooperative effects of the water molecule(s) in the nonreactive region. The catalytic effect of water molecule(s) due to the alleviation of ring strain in the proton transfer process may result from the synergistic effects of rehybridization and charge reorganization from the precoordination complex to the rate-determining transition state structure induced by water molecule. The studies on the effect of temperature on the hydrolysis of COS show that the higher temperature is unfavorable for the hydrolysis of COS. PCM solvation models almost do not modify the calculated energy barriers in a significant way. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008 [source] Computational study of the cooperative effects of nitrogen and silicon atoms on the singlet,triplet energy spacing in 1,3-diradicals and the reactivity of their singlet statesJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 4 2010Takeshi Nakamura Abstract Quantum chemical calculations were performed to investigate the cooperative effect of the nitrogen and silicon atoms on the singlet,triplet energy spacing and the reactivity of the singlet state in 1,2-diazacyclopentane-3,5-diyls and 1,2-diaza-4-silacyclopentane-3,5-diyls. The largest singlet,triplet energy gap (,=,,36.1,kcal/mol) found so far in localized 1,3-diradicals was in the C2v symmetry of 4,4-difluoro-1,2-diaza-4-silacyclopentane-3,5-diyl at the UB3LYP/6-31G(d) level of theory. The cooperative effect was also found in the energy differences of singlet diradicals with the corresponding ring-closing compounds, bicyclo[2.1.0]pentane derivatives. The singlet state of the 1,2-diaza-4-silacyclopentane-3,5-diyls was calculated to be energetically more stable than the ring-closing compound. The notable finding on the stability of the singlet diradicals may be attributed to the resonance structures that specifically stabilize the singlet state of diradicals. The computational studies predict that the singlet 1,2-diaza-4-silacyclopentane-3,5-diyl is a persistent molecule under conditions without intermolecular-trapping reagents. Copyright © 2010 John Wiley & Sons, Ltd. [source] Chemiluminescent picture of diphenyleneiodonium-inhibited NADPH oxidase: a bimodal process and its logistic,exponential model-based descriptionLUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 4 2007Bonawentura Kochel Abstract A chemiluminescence (CL) study of diphenyleneiodonium-inhibited NADPH oxidase was performed on a cellular system containing neutrophils stimulated by phorbol myristate acetate, indicating a complex bimodal structure of CL processes corresponding to different stages of the inhibition. The complex structure of these processes was described by a superposition of two logistic,exponential (LE) models, characterizing these processes as bimodal ones. To determine the mechanistic foundation of the LE model-described processes, a generalized form of the second-order dynamic system of CL reactions, the solution to which corresponds to the LE model, was constructed. The diphenyleneiodonium effects on neutrophil NADPH oxidase were separated from the total bimodal CL of the whole measurement system by the use of difference CL processes. These difference processes were also found to be bimodal; thus, inhibitor-induced reduction of CL could be described by a second-order dynamic system. The rate constants and initial concentrations in this dynamic system were determined by the least squares method applied to numerical solutions approximating the difference processes. Using interrelations between the parameters of the dynamic system, cooperative effects in the inhibitor reactions with NADPH oxidase were found and described quantitatively. Other evidences of cooperativity were obtained from integral characteristics of the CL reduction process, i.e. dose,response and progress curves, determined by numerical integration of the LE models constituting the superposition. On this basis, it was also possible to detect a specific binding of the inhibitor to the enzyme. Finally, putative reaction mechanisms suggested by the model obtained were considered and compared with those known at present. Copyright © 2007 John Wiley & Sons, Ltd. [source] Three-dimensional distribution of no sources in a primary mechanosensory integration center in the locust and its implications for volume signalingTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 15 2010Daniel Münch Abstract Nitric oxide (NO) is an evolutionarily conserved mediator of neural plasticity. Because NO is highly diffusible, signals from multiple sources might combine in space and time to affect the same target. Whether such cooperative effects occur will depend on the effective signaling range and on the distances of NO sources to one another and to their targets. These anatomical parameters have been quantified in only few systems. We analyzed the 3D architecture of NO synthase (NOS) expression in a sensory neuropil, the ventral association center (VAC) of the locust. High-resolution confocal microscopy revealed NOS immunoreactive fiber boutons in submicrometer proximity to both the axon terminals of sensory neurons and their postsynaptic target, interneuron A4I1. Pharmacological manipulation of NO signaling affected the response of A4I1 to individual wind-puff stimuli and the response decrement during repetitive stimulation. Mapping NOS immunoreactivity in defined volumes around dendrites of A4I1 revealed NOS-positive fiber boutons within 5 ,m of nearly every surface point. The mean distances between neighboring NOS-boutons and between any point within the VAC and its nearest NOS-bouton were likewise about 5 ,m. For an NO signal to convey the identity of its source, the effective signaling range would therefore have to be less than 5 ,m, and shorter still when multiple boutons release NO simultaneously. The architecture is therefore well suited to support the cooperative generation of volume signals by interaction between the signals from multiple active boutons. J. Comp. Neurol. 518:2903,2916, 2010. © 2010 Wiley-Liss, Inc. [source] Three-dimensional distribution of NO sources in a primary mechanosensory integration center in the locust and its implications for volume signalingTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 15 2010Daniel Münch Abstract Nitric oxide (NO) is an evolutionarily conserved mediator of neural plasticity. Because NO is highly diffusible, signals from multiple sources might combine in space and time to affect the same target. Whether such cooperative effects occur will depend on the effective signaling range and on the distances of NO sources to one another and to their targets. These anatomical parameters have been quantified in only few systems. We analyzed the 3D architecture of NO synthase (NOS) expression in a sensory neuropil, the ventral association center (VAC) of the locust. High-resolution confocal microscopy revealed NOS immunoreactive fiber boutons in submicrometer proximity to both the axon terminals of sensory neurons and their postsynaptic target, interneuron A4I1. Pharmacological manipulation of NO signaling affected the response of A4I1 to individual wind-puff stimuli and the response decrement during repetitive stimulation. Mapping NOS immunoreactivity in defined volumes around dendrites of A4I1 revealed NOS-positive fiber boutons within 5 ,m of nearly every surface point. The mean distances between neighboring NOS-boutons and between any point within the VAC and its nearest NOS-bouton were likewise about 5 ,m. For an NO signal to convey the identity of its source, the effective signaling range would therefore have to be less than 5 ,m, and shorter still when multiple boutons release NO simultaneously. The architecture is therefore well suited to support the cooperative generation of volume signals by interaction between the signals from multiple active boutons. J. Comp. Neurol. 518:2903,2916, 2010. © 2010 Wiley-Liss, Inc. [source] Synthesis, characterization and hydroformylation activity of 7-azaindolate-bridged dinuclear rhodium(I)phosphines with pendant polar-groupsAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 11 2009Chandra Sekhar Vasam Abstract New dinuclear Rh(I),Phosphines of the types [Rh(µ-azi)(CO)(L)]2 (1,3,7) and [Rh(µ-azi)(L)]2 (8) with pendant polar groups, and a chealated mononuclear compound [Rh(azi-H)(CO)(L)] (2) (where azi = 7-azaindolate, L = polar phosphine) were isolated from the reaction of [Rh(µ-Cl)(CO)2]2 with 7-azaindolate followed by some polar mono - and bis -phosphines (L1,L8). A relationship between ,,31P-NMR and ,(CO) values was considered to define the impact of polar-groups on ,-donor properties of the phosphines. These compounds were evaluated as catalyst precursors in the hydroformylation of 1-hexene and 1-dodecene both in mono- and biphasic aqueous organic systems. While the biphasic hydroformylations (water + toluene) gave exclusively the aldehydes, the monophasic one (aqueous ethanol) showed propensity to form both aldehydes and alcohols. The influence of bimetallic cooperative effects, and ,-donor and hydrophilic properties of the phosphines with pendant polar-groups in enhancing the yields and selectivity of hydroformylation products was emphasized. In addition, when strong ,-donor phosphine was used, the ,-acceptor nature of pyridine ring of 7-azaindolate spacer was found to be a considerable factor in facilitating the facile cleavage of CO group during hydroformylation and in supplementing the cooperative effects. Copyright © 2009 John Wiley & Sons, Ltd. [source] Enhanced differentiation of embryonic stem cells using co-cultivation with hepatocytesBIOTECHNOLOGY & BIOENGINEERING, Issue 6 2008Rebecca N. Moore Abstract We examined the effects of co-cultivated hepatocytes on the hepatospecific differentiation of murine embryonic stem (ES) cells. Utilizing an established mouse ES cell line expressing high or low levels of E-cadherin, that we have previously shown to be responsive to hepatotrophic growth factor stimulation (Dasgupta et al., 2005. Biotechnol Bioeng 92(3):257,266), we compared co-cultures of cadherin-expressing ES (CE-ES) cells with cultured rat hepatocytes, allowing for either paracrine interactions (indirect co-cultures) or both juxtacrine and paracrine interactions (direct co-cultures, random and patterned). Hepatospecific differentiation of ES cells was evaluated in terms of hepatic-like cuboidal morphology, heightened gene expression of late maturation marker, glucose-6-phosphatase in relation to early marker, alpha-fetoprotein (AFP), and the intracellular localization of albumin. Hepatocytes co-cultured with growth factor primed CE-ES cells markedly enhanced ES cell differentiation toward the hepatic lineage, an effect that was reversed through E-cadherin blockage and inhibited in control ES cells with reduced cadherin expression. Comparison of single ES cell cultures versus co-cultures show that direct contact co-cultures of hepatocytes and CE-ES cells maximally promoted ES cell commitment towards hepatodifferentiation, suggesting cooperative effects of cadherin-based juxtacrine and paracrine interactions. In contrast, E-cadherin deficient mouse ES (CD-ES) cells co-cultured with hepatocytes failed to show increased G6P expression, confirming the role of E-cadherin expression. To establish whether albumin expression in CE-ES cells was spatially regulated by co-cultured hepatocytes, we co-cultivated CE-ES cells around micropatterned, pre-differentiated rat hepatocytes. Albumin localization was enhanced "globally" within CE-ES cell colonies and was inhibited through E-cadherin antibody blockage in all but an interfacial band of ES cells. Thus, stem cell based cadherin presentation may be an effective tool to induce hepatotrophic differentiation by leveraging both distal/paracrine and contact/juxtacrine interactions with primary cells of the liver. Biotechnol. Bioeng. © 2008 Wiley Periodicals, Inc. [source] Learning from Directed Evolution: Theoretical Investigations into Cooperative Mutations in Lipase EnantioselectivityCHEMBIOCHEM, Issue 2 2004Marco Bocola Dr. Abstract Molecular modeling with classical force-fields has been used to study the reactant complex and the tetrahedral intermediate in lipase-catalyzed ester hydrolysis in 20 enzyme/substrate combinations. The R and S enantiomers of,-methyldecanoic acid ester served as substrates for the wild-type lipase from Pseudomonas aeruginosa and nine selected mutants. After suitable preparation of initial structures from an available wild-type crystal structure, each system was subjected to 1 ns CHARMM force-field molecular dynamics simulations. The resulting geometric and energetic changes allow interpretation of some experimentally observed effects of mutations, particularly with regard to the "hot spots" at residues 155 and 162. The replacement S155F enhances S enantiopreference through a steric relay involving Leu162. The double mutation S53P + L162G improves S enantioselectivity by creating a new binding pocket for the S enantiomer with an additional stabilizing hydrogen bond to His83. The simulations provide insight into remote and cooperative effects of mutations. [source] | |||||||||||||