Abstract
The interaction of reduced riboflavin-2′,3′,4′,5′-tetrabutyrate with salicylic acid, aspirin, and salicylamide has been spectroscopically investigated to determine the binding mechanism. Hydrogen-1 and carbon-13 nuclear magnetic resonance, infrared, and absorption spectra were measured in chloroform-d and chloroform. The association of the reduced riboflavin with salicylic acid derivatives is different from that oxidized one. Salicylic acid and the reduced riboflavin form a cyclic hydrogen bonded complex through the imino (3-N, 5-N) protons and the carbonyl (2-C, 4-C) oxygens of the isoalloxazine ring of the latter, and the carboxylic hydroxyl proton and carbonyl oxygen of the former. Aspirin and the reduced riboflavin form a complex by the same mode as salicylic acid. Salicylamide forms a cyclic hydrogen bonded complex with the reduced riboflavin through the imino (3-N, 5-N) protons and the carbonyl (2-C, 4-C) oxygens of the isoalloxazine ring, and the amino proton and the carbonyl oxygen of salicaylmide. It appears that both the oxidized and reduced form of riboflavin are associated with salicylic acid derivatives.
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Literature Cited
Pullman, B. and Pullman, A.: Electron structure of the respiratory coenzyme.Proc. Natl. Acad. Sci., USA. 45, 136 (1959).
Grabe, B.: Electron distribution in high-energy phosphate and the transfer of energy from catabolism to anabolism to anabolism.Biochim. Biophys. Acta.,30, 560 (1958).
Shifrin, S.: Charge-transfer and exitation-energy transfer in a model for enzyme-coenzyme interaction.ibid,81, 205 (1964).
Yomosa, S.: Chaige-transfer molecular compounds in biological systems.Progr. Theor. Phys. Suppl.,40, 349 (1967).
Sakurai, T., and Hosoya, H.: Charge-transfer complexes of nicotinamide-adenine dinucleotide analogues and flavin mononucleotide.Biochim. Biophys. Acta.,112, 459 (1966).
Honda, M.: On the electron-transfer in NAD-FMN system.J. Phys. Soc., Japan,31, 1196 (1971).
Brody, T.M.: Action of sodium salicylate and related compounds on tissue metabolismin vitro.J. Pharmacol. Exp. Ther.,117, 39 (1956).
Sproull, D.H.: The glycogenolytic action of sodium salicylate.Br. J. Pharmacol.,9, 262 (1954).
Spenny, J.G.: and Brown, M.: Effect on ASA on gastric mucosa.Gastroenterology,73, 995 (1977).
Fishgold, J.T., Field, J., and Hall, V.E.: Effect of sodium salicylate and acetylsalicylate on mesabolism of rat brain and liverin vitro.Am. J. Physiol.,164, 727 (1951).
Levy, J.: Action of sodium salicylate and sulfadiazine on hyaluronidase.Bull. Soc. Chim. Biol.,28, 338 (1946).
Graham, J.D.P., and Parker, W.A.: Plasma concentration of salicylate.Q. J. Med.,17, 153 (1948).
Galen, F.X., Truchot, R., and Michel, R.: Mechanism d action de 1 acid iodo-4-salicyligue sur la respiration des nitochondries isolees.Biochim. Pharmacol.,23, 1379 (1974).
Millhorn, D.E., Eldridge, F.L., and Waldrop, T.G.: Effects of salicylate and 2,4-dinitrophenol on repiration and metabolism.J. Appl. Physio.,53, 925 (1982).
Millhorn, D.E., Eldridge, F.L., and Waldrop, T.G.: Central neural stimulation of repiration by sodium salicylate.Respiration Physiol.,51, 219 (1983).
Wilson, C.O., Gisvold, O., and Doerge, R.F.:Textbook of Organic Medicinal and Pharmaceutical Chemistry, Lippincot, Philadelphia, Pa., 47 (1977).
Huh, J.W., and YU, B.S.: A spectroscopic study of hydrogen bonding between riboflavin and salicylic acid derivatives.J. Pharm. Soc. Korea,20, 130 (1976).
Yu, B.S., Lee, S.J., and Chung, H.H.: Molecular interaction between riboflavin and salicylic acid darivatives in nonpolar solvents.J. Pharm. Sci.,72, 592 (1983).
Kawano, K., Ohishi, N., Suzuki, A.T., Kyogoku, Y., and Yagi, K.: Nitrogen-15 and carbon-13 NMR of reduced flavins. Comparative study with oxidized flavins.Biochemistry,17, 3584 (1978).
Kyogoku, Y., Kawano, K., Ohishi, N., Suzuki, A.T., and Yagi, K.: Comparison of NMR spectra of the oxidized and reduced forms of flavin.Flavins and Flavoproteins, Yagi, K., Elsevier, Amsterdam, 485 (1980).
YU, B.S., and Kyogoku, Y.: Association of a reduced riboflavin derivative with purines, pyrimidines and nicotinamide.Bull. Chem. Soc., Japan,43, 239 (1970).
Hemmerich, P., and Hass, W.:Reactivity of flavins, Yagi, K., Nagoya, Japan, P.1 (1975).
Ghisla, S., Massey, V., Lhoste, J.M., and Mayhew, S.G.:Reactivity of flavins, Yagi, K., Nagoya, Japan, P.15 (1975).
Lauterbur, P.C.: C13NMR spectroscopy (I). Aromatic hydrocarbons.J. Am. Chem. Soc.,83, 1888 (1961).
Yagi, K., Ohishi, N., Takai, A., Kawano, K., and Kyogoku, K.:Flavins and Flavoproteins, Proc. Int. Sympo., 5th, P.775 (1975).
Grande, H.J., Gast, R., Van Berkei, W.J.H., and Mueller, F.: Carbon-13 NMR study on isoalloxazine and alloxazine derivatives.Helv. Chim. Acta.,60, 367 (1977).
Yagi, K., Ohishi, N., Nishimoto, K., Choi, J.D., and Song, P.S.:Biochemistory,19, 1533 (1980).
Nishimoto, K., Watanabe, Y., and Yagi, K.: Hydrogen bonding of flavoprotein (I). Effect of hydrogen bonding on electronic spectra of flavoprotein.Biochim. Biophys. Acta.,526, 34 (1978).
Sun, M., and Song, P.S.: Excited states and reactivity of 5-dezaflavin comparative studies with flavins.Biochemistry,12, 4663 (1973).
Song, P.S., Choi, J.D., Fagate, R.D., and Yagi, K.:Flavins and flavoproteins, Singer, T.P., Elsevier Amsterdam, P. 381 (1976).
Edmonson, D.E., Barman, B., and Tollin, G.: On the importance of the 5-N position in flavin coenzyme. Properties of free and protein-bound 5-deza analogs.Biochemistry,11, 1133 (1972).
Chassy, B.M., and McCormick, D.B.: Structural requirements of the flavin-adenine dinucleotide for intramolecular complex formation.Biochemistry,4, 2612 (1965).
Massey, V., and Ganther, H.: Interpretation of the absorption spectra of flavoproteins D-amino acid oxidase.ibid,4, 1161 (1965).
Mueller, F., Mayhew, S.G., and Massey, V.: Effect of temperature on the absorption spectra of free and protein-bound flavins.Biochemistry,12, 4654 (1973).
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Yu, B.S., Oh, E.C. & Sohn, D.H. Molecular interaction between a reduced riboflavin derivative and salicylic acid derivatives. Arch. Pharm. Res. 8, 99–107 (1985). https://doi.org/10.1007/BF02857035
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DOI: https://doi.org/10.1007/BF02857035