Synthesis, characterisation and high-performance liquid chromatography of C6-C16 dicarboxylyl-mono-coenzyme A and -mono-carnitine esters.

The synthesis and purification of the mono-coenzyme A and mono-carnitine esters of the homologous series of straight-chain even-numbered dicarboxylic acids (C6-C16) is described. The corresponding 3-hydroxyacyl- and 2-enoyl-CoA esters were prepared enzymatically. A reversed-phase high-performance liquid chromatographic (HPLC) system for the analysis of the intact CoA esters is described and their chromatographic behaviour documented. Reversed-phase HPLC systems for the analysis of the 4-bromophenacyl derivatives of the dicarboxylyl-mono-carnitines and the 4-nitrobenzyl derivatives of the free acids are also described. Some preliminary studies of the metabolism of [U-14C]hexadecanedionoyl-mono-CoA by rat liver peroxisomes and rat skeletal muscle mitochondria are described illustrating the application of these methods.     

Determination of therapeutic oligonucleotides using capillary gel electrophoresis

Oligonucleotides have developed into highly versatile and selective therapeutics over the past 20 years. More than five discrete mechanisms of action have been reported and more than 10 different chemical modifications have been used to extend their in vivo half-life and reduce their toxicity. Capillary gel electrophoresis (CGE) has been used extensively for the quantitative analysis of oligonucleotide therapeutics in both preclinical and clinical studies since the 1990s. The success of CGE is based on its extraordinary resolving power, which allows for the simultaneous determination of the parent drug and its metabolites. More recently, capillary gel electrophoresis has seen renewed interest with the emergence of replaceable gels with single-base resolving power and new capillary electrophoresis-mass spectrometry interfaces. This review discusses the bioanalysis of therapeutic oligonucleotides showing the evolution of the field over the past two decades leading to the current new approaches. Included in this review are topics such as different gel types, sample introduction modes, sample extraction procedures, separation conditions and detection methods used in CGE, along with discussions of the successes and limitations associated with each.     

Increasing the applicability of density functional theory. II. Correlation potentials from the random phase approximation and beyond

Density functional theory (DFT) results are mistrusted at times due to the presence of an unknown exchange correlation functional, with no practical way to guarantee convergence to the right answer. The use of a known exchange correlation functional based on wave-function theory helps to alleviate such mistrust. The exchange correlation functionals can be written exactly in terms of the density-density response function using the adiabatic-connection and fluctuation-dissipation framework. The random phase approximation (RPA) is the simplest approximation for the density-density response function. Since the correlation functional obtained from RPA is equivalent to the direct ring coupled cluster doubles (ring-CCD) correlation functional, meaning only Coulomb interactions are included, one can bracket RPA between many body perturbation theory (MBPT)-2 and CCD with the latter having all ring, ladder, and exchange contributions. Using an optimized effective potential strategy, we obtain correlation potentials corresponding to MBPT-2, RPA (ring-CCD), linear-CCD, and CCD. Using the suitable choice of the unperturbed Hamiltonian, Kohn-Sham self-consistent calculations are performed. The spatial behavior of the resulting potentials, total energies, and the HOMO eigenvalues are compared with the exact values for spherical atoms. Further, we demonstrate that the self-consistent eigenvalues obtained from these consistent potentials used in ab initio dft approximate all principal ionization potentials as demanded by ionization potential theorem.     

ChemInform Abstract: Stabilization of the Pseudo-Benzene N6 Ring with Oxygen.

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