The preparation, characterisation and solubility characteristics of a hydrogen-bonded complex between acyclovir and cytosine.
Acyclovir and cytosine form a Crick-Watson hydrogen-bonded complex in dimethylsulphoxide (DMSO). For the complex formation Acyclovir + cytosine reversible complex the equilibrium constant, K, was determined using NMR spectroscopy to be K = 1.00 +/- 0.07 mol-1 dm3 at 21 degrees C in DMSO. The acyclovir-cytosine complex was formed in DMSO, then diluted with octan-1-ol to leave a 95.3% v/v octan-1-ol/47% v/v DMSO solution, and demonstrated a 12-fold increase in the saturated solubility of acyclovir. This was compared to a solution of acyclovir alone treated in the same manner. This suggests that a complex species of acyclovir with cytosine has a greater lipophilic character than acyclovir alone. Attempts to increase the octan-1-ol/water partition coefficient for acyclovir produced no significant increase with the presence of cytosine. It was argued that no complexation would occur in water due to the rapid exchange of the protons that are involved in the hydrogen-bonded complex. Experiments to isolate the solid acyclovir-cytosine Crick-Watson hydrogen-bonded complex were performed. Spectra and T1 relaxation times obtained during subsequent solid-state 13C NMR experiments provided evidence that a solid complex can be isolated.
Newby
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Reckitt & Colman Pharmaceuticals, Hull, UK.
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D000212:Acyclovir / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003596:Cytosine / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D012995:Solubility
D000998:Antiviral Agents; D003596:Cytosine; D000212:Acyclovir