MEASUREMENT OF LIPOPHILICITY INDEXES BY REVERSED-PHASE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY - COMPARISON OF 2 STATIONARY PHASES AND VARIOUS ELUENTS

Twenty-eight benzene derivatives spanning a broad range of lipophilicities were used as model compounds to examine the optimum stationary phase and eluent conditions for the determination of lipophilic indices by reversed-phase high-performance liquid chromatography. This was assessed by linear regressions comparing published octanol-water partition coefficients with isocratic capacity factors and capacity factors extrapolated to 100% water in the eluent. Methanol-water eluents are always to be preferred to acetonitrile-water and tetrahydrofuran-water eluents. The octadecylsilane (ODS) phase yielded good correlations especially when a masking agent was added to the eluent, but this introduced an additional experimental variable. The octadecyl-polyvinyl copolymer (ODP) phase was just as satisfactory as the ODS phase without the need for a masking agent, and thus appears to be a valuable alternative

Solvent-dependent conformation and hydrogen-bonding capacity of cyclosporin A: Evidence from partition coefficients and molecular dynamics simulations

The partition coefficient of cyclosprin A (CsA) was measured in octanol/water and heptane/water by centrifugal partition chromatography. By comparison with results from model compounds, it was deduced that the hydrogen-bonding capacity of CsA changed dramatically from an apolar solvent (where it is internally H-bonded) to polar solvents (where it exposes its H-bonding groups to the solvent). Molecular dynamics simulations in water and CCl4 support the suggestion that CsA undergoes a solvent-dependent conformational changes and that the interconversion process is slow on the molecular dynamics time scale

Targeting mitochondria with small molecules:The preparation of MitoB and MitoP as exomarkers of mitochondrial hydrogen peroxide

Small molecules can be physicochemically targeted to mitochondria using the lipophilic alkyltriphenylphosphonium (TPP) group. Once in the mitochondria the TPP-conjugate can detect or influence processes within the mitochondrial matrix directly. Alternatively, the conjugate can behave as a prodrug, which is activated by release from the TPP group either using an internal or external instruction. Small molecules can be designed that can be used in any cell line, tissue or whole organism, allow temporal control, and be applied in a reversible dose-dependent fashion. An example is the detection and quantification of hydrogen peroxide in mitochondria of whole living organisms by MitoB. Hydrogen peroxide produced within the mitochondrial matrix is involved in signalling and implicated in the oxidative damage associated with aging and a wide range of age-associated conditions including cardiovascular disease, neurodegeneration, and cancer. MitoB accumulates in mitochondria and is converted into the exomarker, MitoP, by hydrogen peroxide in the mitochondrial matrix. The hydrogen peroxide concentration is determined from the ratio of MitoP to MitoB after a period of incubation, and this ratio is determined by mass spectrometry using d15-MitoP and d15-MitoB as standard. Here we describe the synthesis of MitoB and MitoP and the deuterated standards necessary for this method of quantification