Biomedical subjects

Thomas Buhse

Publications and source records attributed to Thomas Buhse.

7 recordsLinked to original sources

PubMed2007

Enantioselectivity reversal by achiral additives in the Soai reaction: a kinetic understanding.

Numerical kinetic simulations have been employed to understand the origin of enantioselectivity reversal of chiral beta-amino alcohol catalysts occurring in the presence of their achiral analogs in the autocatalytic addition of diisopropylzinc to pyrimidine carbaldehydes (Soai reaction). In a preceding work (Rivera Islas, J.; Lavabre, D.; Grevy, J. M.; HernAndez Lamoneda, R.; Rojas Cabrera, H.; Micheau, J. C.; Buhse, T. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 13743-13748), we provided a possible explanation for the phenomenon of spontaneous mirror-symmetry breaking observed in this reaction. The effect of enantioselectivity reversal, giving rise to steep and abrupt transitions between opposed optically active states, has been identified by our current approach as another manifestation of such mirror-symmetry breaking capability. In the present case, we considered the involvement of the chiral catalyst and its achiral analog in the reaction network. Our modeling indicates that the enantioselectivity reversal can be either caused (i) by an interaction between the chiral and achiral additives or (ii) by an interaction of the customary products of the Soai reaction with the additives. The second option, which stands for the reversible inhibition of the chirally selective autocatalysts by the additives, could also explain a number of further additive effects in the Soai reaction reflecting the extraordinary sensitivity of this system toward the initial addition of almost any, even catalytically inactive, chiral substance.

Catalysis↗

PubMed2005

Mirror-symmetry breaking in the Soai reaction: a kinetic understanding.

Kinetic modeling using nonlinear differential equations is proposed to analyze the spontaneous generation of enantiomeric excess in the autocatalytic addition of diisopropylzinc to prochiral pyrimidine carbaldehydes (Soai reaction). Our approach reproduces experimentally observed giant chiral amplification from an initial enantiomeric excess of <10(-6)% to >60%, high sensitivity and positive response to the presence of minute amounts of chiral initiator at concentrations <10(-14) M, and spontaneous absolute asymmetric synthesis from achiral starting conditions. From our numerical simulations using kinetic schemes derived from the Frank model, including stereospecific autocatalysis and mutual inhibition, we have shown that it is possible to reproduce the mirror-symmetry-breaking behavior of the Soai reaction under batch conditions leading to a bimodal enantiomeric product distribution. Mirror-symmetry breaking was found to be resistant to a loss of stereoselectivity up to 30%. While the mutual inhibition between enantiomers seems to originate from the presence of dimerization equilibria, the exact nature of the autocatalytic stereoselective process still remains to be revealed. From the kinetic viewpoint, simple autocatalysis involving monomers as the catalytic species is consistent with all reported experimental effects of the Soai reaction.

Journal Article↗

PubMed2004

Kinetic analysis of self-replicating peptides: possibility of chiral amplification in open systems.

A simplified kinetic model scheme is presented that addresses the main reactions of two recently reported peptide self-replicators. Experimentally observed differences in the autocatalytic efficiency between these two systems-- caused by variations in the peptide sequences--and the possible effect of chiral amplification under heterochiral reaction conditions were evaluated. Our numerical simulations indicated that differences in the catalytic performance are exclusively due to pronounced variations in the rate parameters that control the reversible and hydrophobic interactions in the reaction system but neither to alterations in the underlying reaction network nor to changes in the stoichiometry of the involved aggregation processes. Model predictions further demonstrated the possible existence of chiral amplification if peptide self-replication is performed under heterochiral reaction conditions. Pointing into the direction of a possible cause for biomolecular homochirality, it was found that in open flow reactors, keeping the system under non-equilibrium conditions, a remarkable amplification of enantiomeric excess could be achieved. According to our modeling, this is due to a chiroselective autocatalytic effect and a meso-type separation process both of which are assumed to be intrinsic for the underlying dynamics of heterochiral peptide self-replication.

Catalysis↗

PubMed2004

Expression of cholera toxin under non-AKI conditions in Vibrio cholerae El Tor induced by increasing the exposed surface of cultures.

The regulatory systems controlling expression of the ctxAB genes encoding cholera toxin (CT) in the classical and El Tor biotypes of pathogenic Vibrio cholerae have been characterized and found to be almost identical. Notwithstanding this, special in vitro conditions, called AKI conditions, are required for El Tor bacteria to produce CT. The AKI conditions involve biphasic cultures. In phase 1 the organism is grown in a still tube for 4 h. In phase 2 the medium is poured into a flask to continue growth with shaking. Virtually no expression of CT occurs if this protocol is not followed. Here we demonstrated that CT expression takes place in single-phase still cultures if the volume-to-surface-area ratio is decreased, both under air and under an inert atmosphere. The expression of key genes involved in the regulation of CT production was analyzed, and we found that the expression pattern closely resembles the in vivo expression pattern.

Air↗

PubMed2003

Kinetic analysis of artificial peptide self-replication. Part I: the homochiral case.

Computational kinetic analysis of a lately discovered homochiral peptide self-replicator is presented. A 6-step kinetic model was designed that addresses the main reactions and hydrophobic interactions involved in this template-directed, autocatalytic system and that gave rise to excellent fitting of 4 previously published independent experimental series. The model sheds light on the mechanistic principle of the reaction system and illustrates directly a number of dynamic properties such as the observed autocatalytic efficiency. It was found that the dynamics are basically governed by two reversible hydrophobic interactions: between the template and a peptide fragment and between two template species. The later association was determined to be considerably more favored, which leads to the predominant presence of the catalytically inactive template dimer in the reaction system. Our results show that the involvement of a template trimer is not necessary to obtain the observed fittings.

Algorithms↗

PubMed2003

Kinetic analysis of artificial peptide self-replication. Part II: the heterochiral case.

A kinetic model has been designed to describe and to analyze the stereoselective behavior of a recently discovered heterochiral template-directed peptide self-replicator by Ghadiri and co-workers [Nature 409 (2001) 797-801]. It turned out that previous assumptions stating that exclusively homochiral species participate in a stereoselective and autocatalytic pathway and that heterochiral species originate only from uncatalyzed background reactions could not be validated by our model. On the contrary, excellent fitting of experimental data indicated that the whole combinatorial variety of possible cross-catalytic processes involving L- and D- peptide species play an important role and need to be taken into account. The system shows no net creation of chiral matter but only a redistribution of the initially present chiral material. Both, the separation of an optically inactive meso-type template dimer and a slight chiroselective autocatalytic effect, contribute to a predicted amplification of enantiomeric excess that, in some cases, can simultaneously result in a substantial amount of optically active matter.

Algorithms↗

PubMed2002

Viscoelasticity in the diffuse electric double layer.

The electroacoustical impedance of the quartz crystal microbalance (QCM) in contact with aqueous electrolyte solutions was measured using the transfer function method in a flow injection system . Measurements of both components of the impedance of the QCM, the resistance R and the inductive reactance XL, have been performed for modified and bare gold and silver surfaces and for different concentrations of several aqueous electrolyte solutions. For the experimental concentration range of 0-50 mM, unexpectedly the QCM impedance does not follow the Kanazawa equation, as is usual for bulk newtonian liquids. This behavior indicates the presence of a nanometric sized viscoelastic layer between the piezoelectric crystal and the bulk electrolyte solution. This layer can only be identified as the Gouy-Chapman diffuse double layer (DDL). Its elasticity and viscosity have been estimated by the measurement of R and XL. The viscoelasticity of the DDL appears to be independent of the chemical nature of the surface and of the solution viscosity but strongly dependent on the surface charge, the bulk electrolyte concentration and the dielectric constant of the solvent.

Journal Article↗