Studies on Molecular Pharmacology of Thiazide Diuretics:Electron Accepting Nature of Thiazide Diuretics, Fluorescence Quenching Ability

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This study aims to clarify the electron accepting nature of thiazide diuretics, which nature was previously pointed out by the authors' quantum chemical (Hückel's Molecular Orbital Method) calculation. The ability of thiazide diuretics to quench pyrene fluorescence was measured to demonstrate their electron accepting nature. Sulfanilamide, chlorothiazide, trichlormethiazide, polythiazide, cyclopenthiazide and diazoxide were dissolved in a pyrene (4×10-4 M/1) ethanol solution, respectively (6×10-4M and 2.5×103 M/1). In these solutions, intensity of fluorescence of pyrene (380 nm) was measured by 360 nm excitation under a nitrogen gas phase by using an AMINCO-BOWMAN or HITACHI MFP-2 fluorospectrophotometer. All thiazide diuretics could quench fluorescence of pyrene, but sulfanilamide and diazoxide could not. Then, 2×10-4, 4×10-4, 8×10-4, 1×10-3, 2×10-3 and 1×10-2 M/1 of hydrochlorothiazide were dissolved in 1×10-4 M/1 of pyrene ethanol solution, respectively. Intensity and life time of pyrene fluorescence were measured by a fluorospectrophotometer and ruby laser excitation in a vacuum phase. The quenching constant of hydrochlorothiazide was estimated to be 1.3×108-6.6×109/mole, sec by this experiment. Since there was no remarkable 360 nm, spectral absorption in all molecules experimented and no spectral changes by mixing thiazide molecules and pyrene, it was fully suggested that an electron of the excited pyrene would be transferred to the thiazide molecule but not to sulfanilamide and diazoxide. Though the quenching constant of hydrochlorothiazide seemed to be rather smaller, the electron accepting nature of thiazide diuretics was experimentally demonstrated and the authors' proposal of the quantum chemical nature of thiazide diuretics obtained by Hückel's Molecular Orbital Method appeared to be accepted. It seems to be very important to correlate the electron accepting nature of thiazide diuretics to their pharmacological action. It might be suggested that thiazide could interfere with the biological electron transfer system, and then could block the energy formation or conversion for the renal tubular electrolyte reabsorption. Otherwise, a thiazide molecule could interfere with the electron donating group of the renal tubular membrane and cause the change in permeability of the membrane. Further studies would be needed.
Japan Society of Clinical Chemistryの論文

Studies on Molecular Pharmacology of Thiazide Diuretics:Electron Accepting Nature of Thiazide Diuretics, Fluorescence Quenching Ability

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