X-ray structures of fifty year old crystals of cholesterol iodide forms I and II

  The molecular framework of steroids was firmly established from the successful X-ray analysis of cholesteryl iodide crystals over fifty years ago. At the time, this was a triumph for the rapidly developing technique of X-ray crystallography. We describe here new analyses of cholesteryl iodide using crystals of forms I and II^(A) which are at least 50 years old. Comparison of these two structures reveals subtle differences in the geometry of the steroid skeleton, the attached side chain and the covalently bound iodine. The crystals of both forms occur in the same monoclinic space group, P2₁, with similar but nevertheless different unit cells, particularly in the b-axis length. As a consequence, there are subtle differences in the packing mechanisms of the two polymorphs. The two forms were originally classified by Bernal and Crowfoot, on the basis of their studies of more than 60 crystals of sterols and sterol derivatives, as “normal, type A - the common form” (corresponding to form II) and “reverse or type B” (corresponding to form I), respectively. Those crystals of form I which have survived for almost 55 years are poor X-ray diffractors at room temperature and have been analysed at liquid N temperature, diffracting well under these conditions. Form II crystals diffract well at room temperature and for this reason the crystals were not cooled. The main differences in geometry occur in the side-chain which is disordered in the room temperature form II crystals, whilst the individual ring conformations in the steroid skeleton are similar, ring A being a strained chair, ring B a 7α/8β half-chair, ring C a symmetrical chair and D a 13β/14α half-chair. (A) Originally denoted Forms B and A respectively. See Additional Note (A) for explanation.

Lyophilized Drug-Loaded Solid Lipid Nanoparticles Formulated with Beeswax and Theobroma Oil

Solid lipid nanoparticles (SLNs) have the potential to enhance the systemic availability of an active pharmaceutical ingredient (API) or reduce its toxicity through uptake of the SLNs from the gastrointestinal tract or controlled release of the API, respectively. In both aspects, the responses of the lipid matrix to external challenges is crucial. Here, we evaluate the effects of lyophilization on key responses of 1:1 beeswax–theobroma oil matrix SLNs using three model drugs: amphotericin B (AMB), paracetamol (PAR), and sulfasalazine (SSZ). Fresh SLNs were stable with sizes ranging between 206.5–236.9 nm. Lyophilization and storage for 24 months (4–8 °C) caused a 1.6- and 1.5-fold increase in size, respectively, in all three SLNs. Zeta potential was >60 mV in fresh, stored, and lyophilized SLNs, indicating good colloidal stability. Drug release was not significantly affected by lyophilization up to 8 h. Drug release percentages at end time were 11.8 ± 0.4, 65.9 ± 0.04, and 31.4 ± 1.95% from fresh AMB-SLNs, PAR-SLNs, and SSZ-SLNs, respectively, and 11.4 ± 0.4, 76.04 ± 0.21, and 31.6 ± 0.33% from lyophilized SLNs, respectively. Thus, rate of release is dependent on API solubility (AMB < SSZ < PAR). Drug release from each matrix followed the Higuchi model and was not affected by lyophilization. The above SLNs show potential for use in delivering hydrophilic and lipophilic drugs.     

An unusual conformational similarity of two peptide folds featuring sulfonamide and carboxamide on the backbone

Two folded peptides featuring carboxamide and sulfonamide at the core of the peptide fold have been shown to possess almost similar conformational features, despite the well-known fact that carboxamides and sulfonamides have strikingly different hydrogen-bonding and geometrical preferences.     

Localization: The effect of a weak magnetic field

The effect of a weak magnetic field on the diffusion of noninteracting electrons in a disordered system is studied in a nonlinear-model context. The effective Lagrangian describing the soft modes of the system in the weak field limit is derived. The result does not have the simple form that has been suggested by several authors. Therefore the crossover of the system under a weak perturbing magnetic field is not analogous to that found in spin systems.     

A comparison of the AMBER*, OPLSAA and HF potential energy surfaces for a series of diastereomeric cyclic urea HIV-1 inhibitors

The LM:MC conformational search method was used to identify the low energy structures on the OPLS-AA/GBSA(water) and AMBER*/GBSA(water) surfaces for a diastereomeric series of cyclic urea molecules that have been shown to be potent inhibitors of the HIV-1 protease enzyme. The lowest energy structures from each search were then subjected to geometry optimization and frequency analysis using the HF/6-311G** method in conjunction with the self-consistent reaction field (SCRF) treatment for water. A comparison of the diastereomeric energies and structures indicates that the OPLSAA/GBSA(water) surface is in good agreement with the HF/6-311G**/SCRF(water) surface.     

The determination of molybdenum in water and biological samples by graphite furnace atomic spectrometry after polyurethane foam column separation and preconcentration

A system for molybdenum separation and enrichment aiming its determination in water and biological samples by graphite furnace atomic absorption spectrometry (GFAAS) is proposed. The procedure is based on the sorption of the molybdenum (VI) thiocyanate complex onto a mini-column packed with polyurethane foam (PUF). The elution is accomplished by a 3.0 mol l⁻¹ nitric acid solution. Flow variables were optimized and an enrichment factor of 10 as well as a limit of detection (LOD) (3 s) of 0.08 μg l⁻¹ in the sample solution were achieved. The coefficient of variation showed values of 3 and 2% for molybdenum solutions of 2.0 and 10.0 μg l⁻¹, respectively. The accuracy of the method was confirmed by the good concordance between found and certified values in the analysis of certified reference materials (CRMs) (CASS-3 Nearshore Seawater, NIST 1547 Peach Leaves, NIST 1515 Apple Leaves and NIST 1572 Citrus Leaves). The procedure was also applied for the molybdenum determination in mineral waters as well as in produced water samples. The results obtained for the mineral water samples compared well with those obtained by ICP-MS. Concerning the produced water samples, in spite of their large salinity, recoveries of 90 to 120% at the 1 μg l⁻¹ were observed.     

Sensitive spectrophotometric determination of ascorbic acid in fruit juices and pharmaceutical formulations using 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (Br-PADAP)

A simple and very sensitive method has been developed for the determination of ascorbic acid based on the oxidation of ascorbic acid to dehydroascorbic acid by iron(III), followed by a complexation of iron(II) with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol(Br-PADAP). The iron(II) complex is formed immediately, with absorption maxima at 560 and 748 nm and a molar absorptivity of 1.31 × 10⁵ l mole^–1cm^–1 and 5.69 × 10⁴ l mole^–1cm^–1, respectively. The ascorbic acid determination is possible with a linear range up to 2.4 μg ml^–1, a calibration sensitivity of 0.744 ml μg^–1 at 560 nm and 0.323 ml μg^–1 at 748 nm, and a detection limit of 15 ng ml^–1 and 44 ng ml^–1, respectively. The procedure was used for the ascorbic acid determination in several fruit juices and pharmaceutical formulations. The results demonstrated a good precision (R.S.D. < 1%) and are in agreement with those obtained with others methods. The Br-PADAP method proposed is six times more sensitive than the method using the iron(II)-1,10-phenanthroline system. Received: 7 May 1996 / Revised: 1 July 1996 / Accepted: 8 August 1996