Skip to main content

Advertisement

SpringerLink
Log in

Solvent Effect on the Photolysis of Riboflavin

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The kinetics of photolysis of riboflavin (RF) in water (pH 7.0) and in organic solvents (acetonitrile, methanol, ethanol, 1-propanol, 1-butanol, ethyl acetate) has been studied using a multicomponent spectrometric method for the assay of RF and its major photoproducts, formylmethylflavin and lumichrome. The apparent first-order rate constants (k obs) for the reaction range from 3.19 (ethyl acetate) to 4.61 × 10−3 min−1 (water). The values of k obs have been found to be a linear function of solvent dielectric constant implying the participation of a dipolar intermediate along the reaction pathway. The degradation of this intermediate is promoted by the polarity of the medium. This indicates a greater stabilization of the excited-triplet states of RF with an increase in solvent polarity to facilitate its reduction. The rate constants for the reaction show a linear relation with the solvent acceptor number indicating the degree of solute–solvent interaction in different solvents. It would depend on the electron-donating capacity of RF molecule in organic solvents. The values of k obs are inversely proportional to the viscosity of the medium as a result of diffusion-controlled processes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Abraham MH. Solvent effects on reaction rates. Pure Appl Chem. 1985;57:1055–64.

    Article  CAS  Google Scholar 

  2. Adams WP, Kostenbauder HB. Phenoxybenzamine stability in aqueous ethanolic solutions. II. Solvent effects on kinetics. Int J Pharm. 1985;25:313–27.

    Article  CAS  Google Scholar 

  3. Ahmad I, Anwar Z, Iqbal K, Ali SA, Mirza T, Khurshid A, et al. Effect of acetate and carbonate buffers on the photolysis of riboflavin in aqueous solution: a kinetic study. AAPS PharmSciTech. 2014;15:550–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Ahmad I, Bano R, Musharraf SG, Ahmed S, Sheraz MA, Arfeen QU, et al. Photodegradation of moxifloxacin in aqueous and organic solvents: a kinetic study. AAPS PharmSciTech. 2014;15:1588–97.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Ahmad I, Bano R, Musharraf SG, Sheraz MA, Ahmed S, Tahir H, et al. Photodegradation of norfloxacin in aqueous and organic solvents: a kinetic study. J Photochem Photobiol A Chem. 2015;302:1–10.

    Article  CAS  Google Scholar 

  6. Ahmad I, Bano R, Sheraz MA, Ahmed S, Mirza T, Ansari SA. Photodegradation of levofloxacin in aqueous and organic solvents: a kinetic study. Acta Pharm. 2013;63:221–7.

    Article  Google Scholar 

  7. Ahmad I, Fasihullah Q, Vaid FHM. Photolysis of formylmethylflavin in aqueous and organic solvents. Photochem Photobiol Sci. 2006;5:680–5.

    Article  CAS  PubMed  Google Scholar 

  8. Ahmad I, Fasiullah Q, Noor A, Ansari IA, Ali QNM. Photolysis of riboflavin in aqueous solution: a kinetic study. Int J Pharm. 2004;280:199–208.

    Article  CAS  PubMed  Google Scholar 

  9. Ahmad I, Mirza T, Iqbal K, Ahmed S, Sheraz MA, Vaid FHM. Effect of pH, buffer and viscosity on the photolysis of formylmethylflavin: a kinetic study. Aust J Chem. 2013;66:579–85.

    CAS  Google Scholar 

  10. Ahmad I, Rapson HDC. Multicomponent spectrophotometric assay of riboflavin and photoproducts. J Pharm Biomed Anal. 1990;8:217–23.

    Article  CAS  PubMed  Google Scholar 

  11. Ahmad I, Rapson HDC, Heelis PF, Phillips GO. Alkaline hydrolysis of 7, 8-dimethyl-10(formylmethyl)-isoalloxazine. A kinetic study. J Org Chem. 1980;45:31–3.

    Article  Google Scholar 

  12. Ahmad I, Tollin G. Solvent effects on flavin electron transfer reactions. Biochemistry. 1981;20:5925–8.

    Article  CAS  PubMed  Google Scholar 

  13. Ahmad I, Vaid FHM. Photochemistry of flavins in aqueous and organic solvents. In: Silva E, Edwards AM, editors. Flavins photochemistry and photobiology. Cambridge: Royal Society of Chemistry; 2006. p. 13–40.

    Google Scholar 

  14. Amis ES, Hinton JF. Solvent effects on chemical phenomena. New York: Academic; 1973.

    Google Scholar 

  15. Amis ES, Hinton JF. Solvent effect on chemical phenomena. New York: Academic; 1973.

    Google Scholar 

  16. Baker SK, Niazi S. Stability of aspirin in different media. J Pharm Sci. 1983;72:1024–6.

    Article  Google Scholar 

  17. Brennan TV, Clarke S. Spontaneous degradation of polypeptides at aspartyl and asparaginyl residues. Effects of solvent dielectric. Protein Sci. 1993;2:331–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Buncel E, Stairs RA, Wilson H. The role of the solvent in chemical reactions. 3rd ed. New York: Oxford University Press; 2003.

    Google Scholar 

  19. Caporossi A, Mazzotta C, Baiocchi S, Tomaso C. Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. Am J Opthal. 2010;149:585–93.

    Article  CAS  Google Scholar 

  20. Choe E, Huang R, Min DB. Chemical reactions and stability of riboflavin in food. J Food Sci. 2005;70:R28–36.

    Article  CAS  Google Scholar 

  21. Connors KA, Amidon GL, Stella VJ. Chemical stability of pharmaceuticals a handbook for the pharmacist. 2nd ed. New York: Wiley; 1986. p. 38–41.

    Google Scholar 

  22. Fall HH, Petering HG. Metabolic inhibitors. 1. 6,7-Dimethyl-9-formylmethylisoalloxazine, 6,7-dimethyl-9-(12-hydroxyethyl)-isoalloxazine and derivatives. J Am Chem Soc. 1956;78:377–81.

    Article  CAS  Google Scholar 

  23. Fukumachi C, Sakurai Y. Vitamin B2 photolysis. V. The photolytic formation of 6, 7-dimethylflavin-9-acetic acid ester from riboflavin. Vitamins (Kyoto). 1954;7:939–43.

    CAS  Google Scholar 

  24. Ghanem AH, Hassan ES, Hamdi AA. Stability of indomethacin solubilized system. Pharmazie. 1979;34:406–7.

    CAS  PubMed  Google Scholar 

  25. Hatchard CG, Parker CA. A new sensitive chemical actinometer. II. Potassium ferrioxalate as a standard chemical actinometer. Proc Roy Soc (Lond). 1956;A235:518–36.

    Article  Google Scholar 

  26. Heelis PF. The photophysical and photochemical properties of flavin (isoalloxazines). Chem Soc Rev. 1982;11:15–39.

    Article  CAS  Google Scholar 

  27. Heelis PF. The photochemistry of flavins. In: Muller F, editor. Chemistry and biochemistry of flavoenzymes. Boca Raton: CRC Press; 1991. p. 171–93.

    Google Scholar 

  28. Heitele H. Dynamic solvent effects on electron transfer reactions. Angew Chem Int Ed Engl. 1993;32:359–77.

    Article  Google Scholar 

  29. Hou JP, Poole JW. β-lactam antibiotics: their physicochemical properties and biological activities in relation to structure. J Pharm Sci. 1969;60:503–32.

    Article  Google Scholar 

  30. Hussain A, Truelove J. Effect of hydroxyl group substituents on pyran ring on hydrolysis rate of benzoates: 2-tetrahydropyranyl benzoate. J Pharm Sci. 1979;65:235–66.

    Article  Google Scholar 

  31. Ikeda K. Studies on decomposition and stabilization of drugs in solution. IV. Effect of dielectric constant on the stabilization of barbiturate in alcohol-water mixtures. Chem Pharm Bull. 1960;8:504–9.

    Article  CAS  Google Scholar 

  32. Insinska-Rak M, Golczak A, Sikorski M. Photochemistry of riboflavin derivatives in methanolic solutions. J Phys Chem. 2012;116:1199–207.

    Article  CAS  Google Scholar 

  33. Insinska-Rak M, Sikorski M. Riboflavin interactions with oxygen-survey from the photochemical perspective. Chem Eur J. 2014;20:15280–91.

    Article  CAS  PubMed  Google Scholar 

  34. Koziol J. Studies on flavins in organic solvents–II. Photodecomposition of riboflavin in the presence of oxygen. Photochem Photobiol. 1966;5:55–62.

    Article  CAS  Google Scholar 

  35. Koziol J. Studies on flavins in organic solvents–I. Spectral characteristics of riboflavin, riboflavin tetrabutyrate and lumichrome. Photochem Photobiol. 1966;5:41–54.

    Article  CAS  Google Scholar 

  36. Kurtin WE, Latino MA, Song PS. A study of photochemistry of flavins in pyridine and with a donor. Photochem Photobiol. 1967;6:247–59.

    Article  CAS  PubMed  Google Scholar 

  37. Laidler KJ. Chemical kinetics. 3rd ed. New York: Harper & Row; 1987. p. 183–95.

    Google Scholar 

  38. Laidler KJ. Chemical kinetics. 3rd ed. New York: Harper & Row; 1987. p. 279–80.

    Google Scholar 

  39. Mao YP, Tao XL, Lipsky PE. Analysis of the stability and degradation products triptolide. J Pharm Pharmcol. 2000;52:3–12.

    Article  CAS  Google Scholar 

  40. Marcus AD, Taraszka AJ. A kinetic study of the specific hydrogen ion catalyzed solvolysis of chloramphenicol in water-propylene glycol systems. J Pharm Sci. 1959;48:77–84.

    Article  CAS  Google Scholar 

  41. Montessori V, Press N, Harris M, Akagi L, Montaner JSG. Adverse effect of antiretroviral therapy for HIV infection. CMAJ. 2004;170:229–38.

    PubMed Central  PubMed  Google Scholar 

  42. Moore WM, Ireton RC. The photochemistry of riboflavin, V. The photodegradation of isoalloxazines in alcoholic solvents. Photochem Photobiol. 1977;25:347–56.

    Article  CAS  PubMed  Google Scholar 

  43. Owen WR, Stewart PJ. Kinetics and mechanism of chlorambucil hydrolysis. J Pharm Sci. 1979;68:992–6.

    Article  CAS  PubMed  Google Scholar 

  44. Parker AJ. Protic-dipolar aprotic solvent effects on rates of bimolecular reactions. Chem Rev. 1969;69:1–32.

    Article  CAS  Google Scholar 

  45. Peng Z, HaiXia L, SiDe Y, WenFeng W. Effect of pH and polarity on the excited states of norfloxacin and its 4-N-acetyl derivative: a steady state and time-resolved study. Sci China Chem. 2014;57:409–16.

    Article  Google Scholar 

  46. Reichardt C. Solvent effects on chemical reactivity. Pure Appl Chem. 1982;54:1867–84.

    Article  CAS  Google Scholar 

  47. Reichardt C. Solvents and solvent effects in organic chemistry. 2nd ed. New York: VCH Publishers; 1988.

    Google Scholar 

  48. Roseman TJ, Sims B, Stehle RG. Stability of prostaglandins. Am J Hosp Pharm. 1973;30:236–9.

    CAS  PubMed  Google Scholar 

  49. Schmid R, Sapunov VN. Non-formal kinetics: in search of chemical reactions pathways (monograph in modern chemistry). Weinheim: Verlag Chemie; 1982. p. 123–54.

    Google Scholar 

  50. Schmidt WC. Light-induced redox cycles of flavins in various alcohol/acetic acid mixtures. Photochem Photobiol. 1982;36:699–703.

    Article  CAS  Google Scholar 

  51. Sheraz MA, Kazi SH, Ahmed S, Anwar Z, Ahmad I. Photo, thermal and chemical degradation of riboflavin. Beilstein J Org Chem. 2014;10:1999–2012.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Sheraz MA, Kazi SH, Ahmed S, Qadeer K, Khan MF. Multicomponent spectrometric analysis of riboflavin and photoproducts and their kinetic applications. Cent Eur J Chem. 2014;12:635–42.

    Article  CAS  Google Scholar 

  53. Sikorska E, Koziolowa A, Sikorski M, Siemiarczuk A. The solvent effect on the excited state proton transfer of lumichrome. J Photochem Photobiol A Chem. 2003;157:5–14.

    Article  CAS  Google Scholar 

  54. Sikorski E, Worrall DR, Bourdelande JI, Sikroski M. Photophysics of lumichrome and its analogs. Polish J Chem. 2003;77:65–73.

    Google Scholar 

  55. Singh S, Gupta RI. Dielectric constant effects on degradation of azothioprine in solution. Int J Pharm. 1988;46:267–70.

    Article  CAS  Google Scholar 

  56. Sinko PJ. Chemical kinetics and stability. In: Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 413–6.

  57. Song PS, Metzler DE. Photochemical degradation of Flavins–IV. Studies of the anaerobic photolysis of riboflavin. Photochem Photobiol. 1967;6:691–709.

    Article  CAS  PubMed  Google Scholar 

  58. Szezesma V, Koziol J. Photolysis of flavin in carboxylic acids. In: Ostrowski W, editor. Flavins and flavoproteins. Physiochemical properties and functions. Warsaw: Polish Scientific Publishers; 1977. p. 117–26.

    Google Scholar 

  59. Tada H. Decomposition reaction of hexamine by acid. J Am Chem Soc. 1960;82:255–63.

    Article  CAS  Google Scholar 

  60. Tan KL. Phototherapy for neonatal jaundice. Acta Paediatr. 1996;85:277–9.

    Article  CAS  PubMed  Google Scholar 

  61. Tonnesen HH. Formulation and stability testing of photolabile drugs. Int J Pharm. 2001;225:1–14.

    Article  CAS  PubMed  Google Scholar 

  62. Turro NJ, Ramamurthy V, Scaierno JC. Modern molecular photochemistry of organic molecules. Sausalito: University Science; 2010. p. 469–74.

    Google Scholar 

  63. Wypych G. Hand book of solvents. 2nd ed. Toronto: Chem Tec Publishing; 2001. p. 577–81.

    Google Scholar 

  64. Yeh MK. Degradation kinetics of neostigmine in solution. Drug Dev Ind Pharm. 2000;26:1221–6.

    Article  CAS  PubMed  Google Scholar 

  65. Yoshioka S, Stella VJ. Stability of drugs and dosage forms. New York: Kluwer Academic/Plenum Publishers; 2000. p. 102–4.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Baqai Institute of Pharmaceutical Sciences, Baqai Medical University, Toll Plaza, Super Highway, Gadap Road, Karachi, 74600, Pakistan

    Iqbal Ahmad, Zubair Anwar, Sofia Ahmed, Muhammad Ali Sheraz & Raheela Bano

  2. Department of Biochemistry, Dow International Medical College, Dow University of Health Sciences, Ojha Campus, Karachi, 74200, Pakistan

    Ambreen Hafeez

Authors
  1. Iqbal Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zubair Anwar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sofia Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Muhammad Ali Sheraz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Raheela Bano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ambreen Hafeez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Muhammad Ali Sheraz.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahmad, I., Anwar, Z., Ahmed, S. et al. Solvent Effect on the Photolysis of Riboflavin. AAPS PharmSciTech 16, 1122–1128 (2015). https://doi.org/10.1208/s12249-015-0304-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-015-0304-2

KEY WORDS

Search

Navigation