Fmoc-DL-Ser(isoamyl)-OH

Zr(OH)4 gels have been prepared by sol-gel method using isoamyl alcohol/ammonia mixture of different concentrations. The nano Zr(OH)4 gel obtained using 80% isoamyl alcohol and diluted ammonia (6%) gave the highest 99Mo distribution coefficient. SEM images indicated a jelly-like appearance of the optimum Zr(OH)4 gel. XRD analysis proved that Zr(OH)4 gel is an amorphous material. HRTEM analysis indicated a particle size of ≤100 nm with the existence of particle aggregates. According to DLS studies, the hydrodynamic diameter was found to be 78.82 nm (with a mean number percentage of 21.1%), while zeta potential was found to be 29.2 mV N2 adsorption/desorption chromatographic analysis calculations stated a BET surface area of 151 m2/g and an average pore diameter of 1.93 nm. Molybdate(VI)-99Mo adsorption process onto the optimum Zr(OH)4 gel was found to follow pseudo 2nd order and (to some extent) film diffusion mass transfer kinetic models. The adsorption isotherm was found to follow Langmuir model. From kinetic and adsorption isotherm studies it could be determined that the optimum Zr(OH)4 gel has Ea, ΔH° and ΔS° values of 31.29, 50 and 0.185 kJ/mol, respectively, in addition to ΔG° values of -5.09, -7.86 and -11.56 kJ/mol at 25, 40 and 60 °C, respectively. Static molybdate(VI)-99Mo capacity (determined from Langmuir adsorption model) was found to be 292.4, 333.3 and 357.1 mg/g at 25, 40 and 60 °C, respectively, while dynamic capacity was found to be 134.3 mg/g at 25 °C.

The solid-phase peptide synthesis (SPPS) of the C-terminal sequence of hGH with one extra Tyr attached to its N-terminus (total of 16 residues with a disulfide bridge) has been accomplished for the first time by optimizing several synthetic parameters. First of all, the two Ser residues (positions 9 and 13 of the molecule) have been introduced as a single amino acid, Fmoc-Ser(ψMe,Mepro)-OH, demonstrating that the acylation of these hindered moieties is possible. This allows us to avoid the use of the corresponding dipeptides, Fmoc-AA-Ser(ψMe,Mepro)-OH, which are very often not commercially available or very costly. The second part of the sequence has been elongated via a double coupling approach using two of the most effective coupling methods (DIC-OxymaPure and HATU-DIEA). Finally, the disulfide bridging has been carried out very smoothly by a chemoselective thiol-disulfide interchange reaction between a SIT (sec-isoamyl mercaptan)-protected Cys residue and the free thiol of the second Cys. The synthesis of this short peptide has evidenced that SPPS is a multifactorial process which should be optimized in each case.

The imidazobenzodiazepine midazolam (MDZ), along with its 1-hydroxy and 4-hydroxy metabolites (1-OH-MDZ, 4-OH-MDZ) can be simultaneously quantitated by electron capture gas-liquid chromatography. After addition of diazepam as internal standard, alkalinized plasma samples are extracted into benzene-isoamyl alcohol. The organic extract is separated, evaporated to dryness, reconstituted, and chromatographed using 3% SP-2250 as the liquid phase. The identity of 4-OH-MDZ, not previously detected in human plasma in unconjugated form, was verified by negative-ion chemical ionization mass spectroscopy. After single oral doses of MDZ administered to humans, concentrations of MDZ and 1-OH-MDZ (alternatively named 1-hydroxymethyl midazolam) were similar, and both compounds were eliminated from plasma in parallel. Concentrations of 4-OH-MDZ were considerably lower, but this metabolite was also eliminated in parallel with the parent compound.