Effects of light intensity, n-alcohols, water-soluble colorants, and solution viscosity on photoisomerization of sorivudine.
Effects of various factors, such as light intensity, polarizability of n-alcohol solvents, addition of colorants, and viscosity of solutions on the kinetics of the photoisomerization of therapeutically effective E-isomer of sorivudine to its less effective Z-isomer were studied. Solutions of known concentrations of E-isomer or Z-isomer in water or in a series of n-alcohols were directly exposed to ultraviolet (UV) A light, or visible light of 400 or 900 foot candles (fc). E-isomer solutions containing various colorants at 1% w/v, or in a series of poloxamer solutions of different viscosities, were also exposed to 400 or 900 fc light. Using the stability-indicating HPLC assay, which showed mass-balance between the starting isomer and the converting isomer, the kinetics of photoisomerization were monitored. The photoisomerization reaction, which takes place on the vinyl side chain, was found to be a first-order reversible reaction. In water, the rate of conversion of E-isomer to Z-isomer was faster than that of Z-isomer to E-isomer, since, E-isomer with higher extinction coefficient absorbed substantially more light than Z-isomer. The rate of photoisomerization increased with the intensity of the visible light and was very rapid in the presence of UV A light (300 to 400 nm), which is to be expected based on the 239 nm and 283 nm absorption maxima of sorivudine. Addition of water-soluble colorants retarded the photoisomerization process significantly, especially as the maximum absorption wavelengths (lambda max) of the colorants approached the UV region. The rate of photoisomerization increased with increasing polarizability (alpha s) of the n-alcohol solvents. Polarizable solvents such as alcohols could compensate for the electron density built up in the excited state, and thus facilitated the photoisomerization process. The rate of photoisomerization decreased as the viscosity of solution increased. This may be attributed to the fact that the twisting of the C=C bond in the excited state can be inhibited by the friction imposed by the viscous medium.
Bristol-Myers Squibb Co., One Squibb Drive, Bldg. 85, P.O. Box 191, New Brunswick, NJ 08903-0191, USA. desaid@BMS.com
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Desai
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Li
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Janjikhel
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Lang
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Jain
D000438:Alcohols / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000737:chemistry*; D004396:Coloring Agents / Q000737:chemistry; D007536:Isomerism; D008027:Light; D010777:Photochemistry; D012995:Solubility; D014783:Viscosity
D000438:Alcohols; D000998:Antiviral Agents; D004396:Coloring Agents; D001086:Arabinofuranosyluracil; C031368:sorivudine