The application of the Huckel Molecular Orbital (HMO) method to the interpretation of experimental results in biochemistry and biology is discussed. Several methods of derivation and application of the semiempirical parameters used in the HMO technique are given, and a table listing the parameter values is included. I N VIEW of the growing interest in the possibility of correlating Hiickel Molecular Orbital (HMO) calculations (38) with biochemical and biological activities (72, 75, 79, 941, and the application of quantum chemistry to drug design (89), the authors have calculated electron charge distributions of selected cholinesterase inhibitors (80) and are in the process of applying quantum chemistry to our search for effective antimalarials. Two restrictions became apparent a t the onset of these calculations: Parameters were assigned to a limited number of heteroatoms only, and the choice of parameters for a specific heteroatom was dependent upon the method of derivation. With this in mind, the authors decided that a useful contribution to the field would be the publication of a table of the currently available semiempirical parameters and their corresponding derivations and applications, so that other workers would not find it necessary to duplicate this relatively tedious search for the "right" parameter. BACKGROUND
The toxicity of a series of esters of acrylic and methacrylic acids was determined in groups of mice, and the resultant LD50 values were analyzed with the use of the mathematical models of Free and Wilson and of Hansch to relate structure of the compounds to toxicity. Both models proved valuable in relating structures to toxicity parameters, but the more useful method for predicting toxicity was the Hansch model.
The title compound, 5, was prepared and found to be a potent diuretic in the rat. At 27 mg/kg, urine output was 250% of the saline control, and the excretion of electrolytes was similar to th^hydrochlorothiazide control. At 80 mg/kg, the potassium excretion was the same as the saline control, and the sodium and chloride excretions more than doubled. Several analogues were prepared and tested. Some show diuretic activity.
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