Virtual darwinian drug design: QSAR inverse problem, virtual combinatorial chemistry, and computational screening

The generation of diversity and its further selection by an external system is a common mechanism for the evolution of the living species and for the current drug design methods. This assumption allows us to label the methods based on generation and selection of molecular diversity as "Darwinian" ones, and to distinguish them from the structure-based, structure-modulation approaches. An example of a Darwinian method is the inverse QSAR. It consists of the computational generation of candidate chemical structures and their selection according to a previously established QSAR model. New trends in the field of combinatorial chemical syntheses comprise the concepts of virtual combinatorial synthesis and virtual or computational screening. Virtual combinatorial synthesis, closely related to inverse QSAR, can be defined as the computational simulation of the generation of new chemical structures by using a combinatorial strategy to generate a virtual library. Virtual screening is the selection of chemical structures having potential desirable properties from a database or virtual library in order to be synthesized and assayed. This review is mainly focused on graph theoretical drug design approaches, but a survey with key references is provided that covers other simulation methods.     

Chromatographic characterization of adult and foetal rat insulin

Foetal rat pancreatic rudiments explanted on day 14 of gestation were grown in organ culture in medium enriched with amino acids. The size of the insulin granules was increased, resulting in an insulin granule volume fraction greater than the volume fraction measured in pancreas grown in vivo. The pancreas was extracted and the insulin compared. Serial dilution curves of extracts of adult pancreas and pancreas grown in vitro are parallel in the insulin radioimmunoassay, whereas extracts of pancreas of foetus developing in utero appear immunologically different. Adult and foetal rat insulin (in utero) were purified using chromatography on OPTI UP C12, cellulose thin-layer chromatography plates, cellulose acetate foil electrophoresis and finally high-performance liquid chromatography. The ratio of insulin I to insulin II was found to be 1.5 for the adult and 2.7 for the foetus. These results show that there is an unequal expression of the two non-allelic genes controlling insulin biosynthesis in foetal and adult rat pancreas.     

Preparation and sedimentation behavior in magnetic fields of magnetite-covered clay particles

This work is devoted to the preparation of magnetite-covered clay particles in aqueous medium. For this purpose, magnetite nanoparticles were synthesized by a coprecipitation method. These magnetic particles are adhered to sodium montmorillonite (NaMt) particles in aqueous suspensions of both materials, by appropriate control of the electrolyte concentrations. The best condition to produce such heteroaggregation corresponds to acid pH and approximately 1 mol/L ionic strength, when the electrokinetic potentials (zeta-potential) of both NaMt and Fe3O4 particles have high enough and opposite sign, as demonstrated from electrophoresis measurements. When a layer of magnetite re-covers the clay particles, the application of an external magnetic field induces a magnetic moment in clay-magnetite particles parallel to the external magnetic flux density. The sedimentation behavior of such magnetic particles is studied in the absence or presence of an external magnetic field in a vertical direction. The whole sedimentation behavior is also strongly affected by the formation of big flocculi in the suspensions under the action of internal colloidal interactions. van der Waals and dipole-dipole magnetic attractions between magnetite-covered clay particles dominate the flocculation processes. The different relative orientation of the clay-magnetite particles (edge-to-edge, face-to-edge, and face-to-face) are discussed in order to predict the most favored flocculi configuration.     

Determination of rate constants and reaction orders with an open-closed flow-injection configuration

A new, very useful application of open-closed configurations to kinetic studies is reported. The multipeak recordings provided by the manifold used, which features a single conventional photometric detector, were used to calculate the rate constants and reaction orders of a chemical system, namely the ligand displacement reaction between the cobalt(II)-EGTA complex and PAR.     

Partially and totally asynchronous algorithms for linear complementarity problems

A unified treatment is given for partially and totally asynchronous parallel successive overrelaxation (SOR) algorithms for the linear complementarity problem. Convergence conditions are established and compared to previous results. Convergence of the partially asynchronous method for the symmetric linear complementarity problem can be guaranteed if the relaxation factor is sufficiently small. Unlike previous results, this relaxation factor interval does not depend explicitly on problem size.This material is based on research supported by the Air Force Office of Scientific Research Grant No. AFOSR-89-0410.The author wishes to thank the referee for pointing out how to improve the bound (12). The same technique can be used to reduce the factorn in Ref. 5, p. 553, to .     

Isolation and Absolute Configuration of β,β-Carotene Diepoxide

The 5,6:5′,6′-diepoxy-5,6:5′,6;-tetrahydro-β,β-carotene, isolated from tubers of a white-fleshed variety of sweet potato (Ipomoea batatas LAM .) has been assigned the (5R,6S,5′R,6′S)-chirality on the basis of its HPLC, UV/VIS, and CD data.     

Manganese pentacarbonyl bromide as candidate for a molecular qubit system operated in the infrared regime

Our concept for a quantum computational system is based on qubits encoded in vibrational normal modes of polyatomic molecules. The quantum gates are implemented by shaped femtosecond laser pulses. We adopt this concept to the new species manganese pentacarbonyl bromide [MnBr(CO)5] and show that it is a promising candidate in the mid-infrared (IR) frequency range to connect theory and experiment. As direct reference for the ab initio calculations we evaluated experimentally the absorption bands of MnBr(CO)5 in the mid-IR as well as the related transition dipole moments. The two-dimensional potential-energy surface spanned by the two strongest IR active modes and the dipole vector surfaces are calculated with density-functional theory. The vibrational eigenstates representing the qubit system are determined. Laser pulses are optimized by multitarget optimal control theory to form a set of global quantum gates: NOT, CNOT, Pi, and Hadamard. For all of them simply structured pulses with low pulse energies around 1 microJ could be obtained. Exemplarily for the CNOT gate we investigated the possible transfer to experimental shaping, based on the mask function for pulse shaping in the frequency regime as well as decomposition into a train of subpulses.