Biomedical subjects

Thomas J Offerdahl

Publications and source records attributed to Thomas J Offerdahl.

3 recordsLinked to original sources

PubMed2005

Multiple-sample probe for solid-state NMR studies of pharmaceuticals.

Solid-state NMR spectroscopy (SSNMR) is an extremely powerful technique for the analysis of pharmaceutical dosage forms. A major limitation of SSNMR is the number of samples that can be analyzed in a given period of time. A solid-state magic-angle spinning (MAS) probe that can simultaneously acquire up to seven SSNMR spectra is being developed to increase throughput/signal-to-noise ratios. A prototype probe incorporating two MAS modules has been developed and spectra of ibuprofen and aspirin have been acquired simultaneously. This version is limited to being a two-module probe due to large amounts of space required for the tuning elements located next to the MAS modules. A new probe design incorporating coaxial transmission lines and smaller MAS modules has been constructed. This probe allows for close proximity of the MAS modules (within 3 cm), adequate proton decoupling power (>50 kHz), and the capability of remote tuning and sample changing. Spectra of hexamethylbenzene (HMB) have been acquired and show signal-to-noise ratios comparable to existing SSNMR probes. Adamantane line widths are also comparable to conventional probe technology. Decoupling powers of 70 kHz have been achieved using a MAS module suitable for 3 cm spacing between modules. Remote tuning has also been achieved with this new coaxial transmission line design. This probe design can be easily scaled to incorporate multiple MAS modules, which is a limitation of the previous design. The number of modules that can be incorporated is only limited by the number of transmission lines that will fit in a cross-sectional diameter of the bore and the axial field length of the magnet.

Complex Mixtures↗

PubMed2005

Reactions of aliphatic thiyl radicals in the solid state: photoisomerization of trans-4,5-dihydroxy-1,2-dithiacyclohexane and oxidation of dithiothreitol.

A description of free-radical reactions in the solid state is important for some processes causing long-term stability problems of natural and synthetic products. Recent studies revealed that, in the solid state, mercaptooctadecanethiyl radicals, C(18)H(37)S., do not abstract a hydrogen atom from mercaptooctadecane, C(18)H(37)SH, but yield perthiyl radicals, C(18)H(37)SS., via a net sulfur transfer (Faucitano et al. ChemPhysChem 2005, 6, 1100-1107). Here, we demonstrate that such a sulfur transfer is not a general phenomenon of thiyl-radical reactions in the solid state, providing experimental evidence for a solid-state hydrogen-transfer reaction between a dithiyl radical, generated through the photolysis of trans-4,5-dihydroxy-1,2-dithiacyclohexane (DTT(ox)), and dithiothreitol. The photolysis of crystalline solid deposits of DTT(ox) yields two isomers of 2,3-dihydroxy-1-mercaptotetrahydrothiophene with a combined quantum yield of Phi(F) = 0.39 +/- 0.02. This quantum yield was increased to Phi(F) = 0.87 +/- 0.13 when the solid deposits contained an additional dithiol, dl-1,4-dimercapto-2,3-butanediol (DTT), at a ratio of DTT/DTT(ox) = 10:1. This increase in quantum yield depended, in part, on the presence of oxygen but was independent of residual moisture in the solid samples. Mechanistically, the formation of 2,3-dihydroxy-1-mercaptotetrahydrothiophene can be rationalized by the H transfer from DTT to a photochemically formed dithiyl radical from DTT(ox), yielding 2 equiv of monothiyl radicals from DTT, followed by a series of radical transformations.

Cyclohexanes↗

PubMed2005

Quantitation of crystalline and amorphous forms of anhydrous neotame using 13C CPMAS NMR spectroscopy.

Although most drugs are formulated in the crystalline state, amorphous or other crystalline forms are often generated during the formulation process. The presence of other forms can dramatically affect the physical and chemical stability of the drug. The identification and quantitation of different forms of a drug is a significant analytical challenge, especially in a formulated product. The ability of solid-state 13C NMR spectroscopy with cross polarization (CP) and magic-angle spinning (MAS) to quantify the amounts of three of the multiple crystalline and amorphous forms of the artificial sweetener neotame is described. It was possible to quantify, in a mixture of two anhydrous polymorphic forms of neotame, the amount of each polymorph within 1-2%. In mixtures of amorphous and crystalline forms of neotame, the amorphous content could be determined within 5%. It was found that the crystalline standards that were used to prepare the mixtures were not pure crystalline forms, but rather a mixture of crystalline and amorphous forms. The effect of amorphous content in the crystalline standards on the overall quantitation of the two crystalline polymorphic forms is discussed. The importance of differences in relaxation parameters and CP efficiencies on quantifying mixtures of different forms using solid-state NMR spectroscopy is also addressed.

Calorimetry, Differential Scanning↗