Re-evaluation of the conformational structure of sulfadiazine species using NMR and ab initio DFT studies and its implication on sorption and degradation.
ABSTRACT In the environment, the sorption and the degradation of organic pollutants are of increasing interest. The investigation of the chemical structures provides a basis for the development of a suitable binding model approach and for the mechanistic understanding of the chemical fate processes. The aim of this study was the identification of different species of the antibiotic compound sulfadiazine (SDZ) using (1)H and (13)C NMR experiments and ab initio density functional theory (DFT) calculations. In the neutral, aprotic solvent dimethylsulfoxide-d(6) (DMSO-d(6)), a new sulfadiazine structure containing an O-H-N hydrogen bond was identified. In the protic solvent water-d(2) and in dependence on pH and the position of the amidogen hydrogen atom nine possible SDZ conformations were analyzed and five structures were identified. Good conformity between theory and calculation of (1)H NMR was observed. Unfortunately, (13)C NMR is not sensitive enough for comparison and differentiation. In order to verify the identified structures, additional NBO/NLMO (natural localized molecular orbital) analyses were conducted (calculation of net atomic charges, bond polarity, atomic valence, and electron delocalization). Finally, conformation optimizations were performed in order to investigate the stability of the SDZ species. We showed that SDZ contains no S=O double bond, but that it has two S-O single bonds. Surprisingly, negative charges were observed at the pyrimidine nitrogen atom. With these results, the known structure of SDZ was revised. Studies of the geometrical structure and the torsion angles showed that SDZ is very flexible and can be easily fitted to the sorbent. These observations would explain the strong sorbance and hence the rapid formation of non-extractable residues in the environment because SDZ acts as a strong ligand. These results show that that the sulfonamide hydrogen is important for the biological activity but the pyrimidine nitrogen and the sulfonamide oxygen is responsible for the sorbance in environment.
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ABSTRACT: Medical substances (pharmaceuticals) are a group of substances that until recently have been exposed to the environment with very little attention. The reason why they may be interesting as environmental micropollutants, is that medical substances are developed with the intention of performing a biological effect. Especially antibiotics used as growth promoters, as feed additives in fish farms are anticipated to end up in the environment. Very little is known about the exposure routes of the medical substances to the environment. Only few investigations have reported findings of medical substances in other field samples than sediment or treated waste water samples. Several substances seem to be persistent in the environment. This paper outlines the different anticipated exposure routes to the environment, summarises the legislation on the subject and gives an outline of present knowledge of occurrence, fate and effect on both the aquatic and terrestrial environments of medical substances. Present knowledge does not reveal if regular therapeutic use may be the source of a substance carried by sewage effluent into the aquatic system, even though clofibrate, a lipid lowering agent, has been identified in ground and tap water samples from Berlin. Further research would be necessary to assess the environmental risk involved in exposing medical substances and metabolites to the environment.Chemosphere 02/1998; 36(2):357-93. · 3.14 Impact Factor
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ABSTRACT: In the course of the routine use of NMR as an aid for organic chemistry, a day-to-day problem is the identification of signals deriving from common contaminants (water, solvents, stabilizers, oils) in less-than-analytically-pure samples. This data may be available in the literature, but the time involved in searching for it may be considerable. Another issue is the concentration dependence of chemical shifts (especially 1H); results obtained two or three decades ago usually refer to much more concentrated samples, and run at lower magnetic fields, than today’s practice. We therefore decided to collect 1H and 13C chemical shifts of what are, in our experience, the most popular “extra peaks” in a variety of commonly used NMR solvents, in the hope that this will be of assistance to the practicing chemist.The Journal of Organic Chemistry 11/1997; 62(21):7512-7515. · 4.56 Impact Factor