No abstract

A kinetic model of spontaneous amplification of enantiomeric excess in the autocatalytic addition of diisopropylzinc to prochiral pyrimidine carbaldehydes is extended by a negative feedback process. Simulations based on the extended model result in large-amplitude oscillations both in a continuous-flow stirred tank reactor (CSTR) and in a semibatch configuration under optimized initial conditions. When sustained oscillations are maintained in a CSTR, no enantiomeric product distribution could be observed in the calculated series; the system keeps its initial enantiomeric ratio endlessly. During damped oscillations, or steady-state conditions, however, chiral amplification from a very small initial enantiomeric excess to more than 99% occurs in a semibatch configuration. Calculations indicated spontaneous enantiomeric product enrichment (i.e., accumulation of one of the enantiomers at the cost of the other one) from strictly achiral starting conditions in a semibatch configuration due to the inherent numerical error of the integrator method, which can be regarded as a model of the statistical fluctuation in the numbers of enantiomeric molecules.

Voltage-dependent calcium channels are located in the plasma membrane and form a highly selective conduit by which Ca2+ ions enter all excitable cells and some nonexcitable cells. Extensive characterization studies have revealed the existence of one low (T) and five high-voltage-activated calcium channel types (L, N, P, Q, and R). The high voltage-activated calcium channels have been found to exist as heteromultimers, consisting of an alpha1, beta, alpha2/delta, and gamma subunit. Molecular cloning has revealed the existence of 10 channel transcripts, and expression of these cloned calcium channel genes has shown that basic voltage-activated calcium channel function is strictly carried by the corresponding alpha1 subunits. In turn, the auxiliary subunits serve to modulate calcium channel function by altering the voltage dependence of channel gating, kinetics, and current amplitude, thereby creating a likelihood for calcium channels with multiple properties. Although for calcium channels to be effective, Ca2+ ions must enter selectively through the pore of the alpha1-subunit, bypassing competition with other extracellular ions. The structural determinants of this highly selective Ca2+ filter reside within the four glutamic acid residues located at homologous positions within each of the four pore-forming segments. Together, these residues form a single or multiple Ca2+ affinity site(s) that entrap calcium ions, which are then electrostatically repulsed through the intracellular opening of the pore. This mechanism of high-selectivity calcium filtration, the spatial arrangement of pore glutamic acid residues, and the coordination chemistry of calcium binding are discussed in this review.

Natural-abundance isotopic substitution in isotopically prochiral groups of otherwise achiral molecules can provide stochastically formed enantiomeric excesses which exceed the sensitivity threshold of sensitive asymmetric autocatalytic (Soai-type) reactions. This kind of induction of chirality should be taken into consideration in in vitro model experiments and offer a new kind of entry into primary prebiotic or early biotic enantioselection in the earliest stages of molecular evolution.

Enantiomeric excesses obtained in absolute enantioselective synthesis by chiral autocatalysis (Soai-reaction) were statistically analyzed. Two sets of parallel experiments, which were performed under chemically different conditions, are available. One group contains 37, while the other contains 84 preparative results. The former group shows some interesting tendencies but does not give conclusive statistical results. The sample of 84 parallel experiments, providing 39 R- and 45 S-excesses have shown that these data represent two distinct, non-symmetric sets with different non-Gaussian distributions. Clear S preference was found.