Solid state NMR of sulfa-drugs

Abstract

This work has been a study of systems, mostly of sulfa-drugs, showing polymorphic behaviour. Using different means as solid state NMR, X-ray analysis, and theoretical calculations, we have seen how it is possible to understand results obtained from the different techniques, proving how the study of polymorphic systems needs cooperative advice from the different techniques that are able to detect polymorphic differences. Within the sulfa-drugs I have been mostly concentrating on sulfanilamide, studying (^13)C and (^15)N solid state NMR spectra of the different polymorphs. The NMR parameters that have been most interesting to study, have been the relaxation times that have revealed complicated motion of the molecule despite it being a small molecule. In order to obtain detailed information from (^15)N spectra it has been necessary to enrich the samples and this has enabled a study of the shielding tensors of the nitrogens in the molecule. (^13)C spectra were also recorded of systems studied sulfathiazole solvates that proved to show some of the same solid state effects in the NMR spectra as sulfanilamide. Shielding calculations have proved to be still limited in order to obtain reliable information on the shielding of both and (^13)C (^15)N nuclei but considering hydrogen-bonded molecules, as opposed to isolated molecules, seemed to have improved the calculations quite a lot, so that some idea of intermolecular effects could be deducted. Exact positions of the hydrogen has proved to be essential as well in order to improve the calculations. Finally a case study for the REDOR pulse sequence has been carried out. Different attempts to understand the effects influencing this particular experiment have been carried out on 20% and 99% doubly enriched glycine, as well as on a particular sample, doubly enriched BRL55834, but the internuclear distances measured with this technique still displayed some uncertainties that made results not thoroughly reliable.