Desai D, Li D, Janjikhel R, Lang B, Jain N
Bristol-Myers Squibb Co., One Squibb Drive, Bldg. 85, P.O. Box 191, New Brunswick, NJ 08903-0191, USA.
Pharm Dev Technol. 2001;6(1):99-106. doi: 10.1081/pdt-100000047.
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.
研究了各种因素，如光强度、正醇溶剂的极化率、着色剂的添加以及溶液粘度对治疗有效的索立夫定E-异构体向其活性较低的Z-异构体光异构化动力学的影响。已知浓度的E-异构体或Z-异构体在水或一系列正醇中的溶液直接暴露于紫外线（UV）A光或400或900英尺烛光（fc）的可见光下。含有1%w/v各种着色剂的E-异构体溶液，或在一系列不同粘度的泊洛沙姆溶液中，也暴露于400或900 fc光下。使用稳定性指示HPLC测定法监测光异构化动力学，该方法显示起始异构体和转化异构体之间的质量平衡。发现发生在乙烯基侧链上的光异构化反应是一级可逆反应。在水中，E-异构体向Z-异构体的转化速率比Z-异构体向E-异构体的转化速率快，因为具有较高消光系数的E-异构体比Z-异构体吸收的光多得多。光异构化速率随可见光强度的增加而增加，并且在UV A光（300至400 nm）存在下非常快，这基于索立夫定的239 nm和283 nm吸收最大值是可以预期的。添加水溶性着色剂显著延迟了光异构化过程，特别是当着色剂的最大吸收波长（λmax）接近紫外区域时。光异构化速率随正醇溶剂极化率（αs）的增加而增加。像醇这样的可极化溶剂可以补偿激发态中积累的电子密度，从而促进光异构化过程。光异构化速率随着溶液粘度的增加而降低。这可能归因于这样一个事实，即激发态下C=C键的扭曲可以被粘性介质施加的摩擦力抑制。
