Comparison of the acis-base properties of 5- and 6-uracilmethylphosphonate (5Umpa2- and 6Umpa2-) and some related compounds. Evidence for intramolecular hydrogen-bond formation in aqueous solution between (N1)H and the phosphonate group of 6Umpa2-

The acidity constants of 5-uracilmethylphosphonic acid, H2(5Umpa), and 6-uracilmethylphosphonic acid, H2(6Umpa), were determined by potentiometric pH titrations in aqueous solution (25 °C; I = 0.1 M, NaNO3). Comparison of these constants with those of related uracil derivatives (partly taken from the literature) allows the conclusion that an intramolecular hydrogen bond is formed between (N1)H and the phosphonate group of 6Umpa2−; the formation degree of this hydrogen-bonded isomer is estimated to be 86 ± 7%. The X-ray crystal structure analysis of H2(6Umpa) is reported but this solid state structure is dominated by intermolecular hydrogen bonds. In the context of the properties of 5Umpa2− and 6Umpa2− those of uracil are also discussed and from various comparisons of acidity constants it is concluded that deprotonation of uracil may occur at (N3)H as well as at (N1)H but that the (N3)deprotonated species dominates with about 80% in aqueous solution at 25 °C and I = 0.1 M (Na+). The search for other examples of uracil derivatives which allow hydrogen-bond formation in aqueous solution has led to orotic acid (= 6-uracilcarboxylic acid; [H(6Urca)]) and 5-uracilcarboxylic acid [H(5Urca)]; based on acidity constant comparisons it is concluded that in aqueous solution (25 °C; I = 0.1 M, KCl) H(5Urca) exists to about 92 ± 10% as a species with a hydrogen bond between (C5)COOH and (C4)O, and 6Urca− to about 95 ± 5% as a species with a hydrogen bond between (C6)COO− and (N1)H. The importance of intramolecular hydrogen-bond formation to the acid–base properties of compounds in solution is briefly emphasized. DOI: https://doi.org/10.1039/b101078f Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-76234 Published Version Originally published at: Moreno-Luque, C F; Freisinger, Eva; Griesser, R; Ochocki, J; Lippert, Bernhard; Sigel, H (2001). Comparison of the acis-base properties of 5and 6-uracilmethylphosphonate (5Umpa2and 6Umpa2-) and some related compounds. Evidence for intramolecular hydrogen-bond formation in aqueous solution between (N1)H and the phosphonate group of 6Umpa2-. Royal Chemical Society. Journal. Perkin Transactions 2, 10:2005-2011. DOI: https://doi.org/10.1039/b101078f Comparison of the acid–base properties of 5and 6-uracilmethylphosphonate (5Umpa and 6Umpa ) and some related compounds. Evidence for intramolecular hydrogen-bond formation in aqueous solution between (N1)H and the phosphonate group of 6Umpa Cristóbal F. Moreno-Luque, Eva Freisinger,† Burkhard Costisella, Rolf Griesser, Justyn Ochocki, Bernhard Lippert* and Helmut Sigel* a Institute of Inorganic Chemistry, University of Basel, Spitalstrasse 51, CH-4056 Basel, Switzerland. E-mail: [email protected] b Department of Chemistry, University of Dortmund, Otto-Hahn-Strasse 6, D-44227 Dortmund, Germany. E-mail: [email protected] c Institute of Chemistry, Medical University, Muszyńskiego 1, PL-90-151 Lódź, Poland. E-mail: [email protected] Received (in Cambridge, UK) 31st January 2001, Accepted 19th July 2001 First published as an Advance Article on the web 10th September 2001 The acidity constants of 5-uracilmethylphosphonic acid, H2(5Umpa), and 6-uracilmethylphosphonic acid, H2(6Umpa),‡ were determined by potentiometric pH titrations in aqueous solution (25 C; I = 0.1 M, NaNO3). Comparison of these constants with those of related uracil derivatives (partly taken from the literature) allows the conclusion that an intramolecular hydrogen bond is formed between (N1)H and the phosphonate group of 6Umpa ; the formation degree of this hydrogen-bonded isomer is estimated to be 86 ± 7%. The X-ray crystal structure analysis of H2(6Umpa) is reported but this solid state structure is dominated by intermolecular hydrogen bonds. In the context of the properties of 5Umpa and 6Umpa those of uracil are also discussed and from various comparisons of acidity constants it is concluded that deprotonation of uracil may occur at (N3)H as well as at (N1)H but that the (N3)-deprotonated species dominates with about 80% in aqueous solution at 25 C and I = 0.1 M (Na ). The search for other examples of uracil derivatives which allow hydrogen-bond formation in aqueous solution has led to orotic acid (= 6-uracilcarboxylic acid; [H(6Urca)]) and 5-uracilcarboxylic acid [H(5Urca)]; based on acidity constant comparisons it is concluded that in aqueous solution (25 C; I = 0.1 M, KCl) H(5Urca) exists to about 92 ± 10% as a species with a hydrogen bond between (C5)COOH and (C4)O, and 6Urca to about 95 ± 5% as a species with a hydrogen bond between (C6)COO and (N1)H. The importance of intramolecular hydrogen-bond formation to the acid–base properties of compounds in solution is briefly emphasized.