A study of the nitroprusside anion and some of its analogues
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Sodium nitroprusside is a potent vasodilator and is widely used for lowering the blood pressure during major surgery. The physiological response is said to occur due to a nitrosation reaction at the smooth muscle membrane. The use of sodium nitroprusside has been restricted due to its ability' to release toxic cyanide in-vivo and in-vitro, which can cause severe complications during surgery. Chapter one is a study of the aqueous chemistry of sodium nitroprusside with amines and thiols. It is shown that steric factors play an important role and that thiols are more reactive than amines. The information is used to evaluate the chemical changes expected at the smooth muscle membrane and possible mechanisms for biochemical action. If the toxicity of nitroprusside anion cannot be aleviated the information can be used to evaluate the potential of other inorganic complexes as potential hypertensive agents. Chapter two deals with the biochemical and medical problems associated with sodium nitroprusside therapy. The interaction of the complex with human erytthrocytes is explored and the reasons for cyanide release are discussed. The toxicity associated with the complex is shown to be impossible to eradicate completely and short term measures to minimise the effects are given. Chapter three explores the implications of the nitrosyl stretching frequency and how its value could be used to indicate whether a compound would be expected to exhibit nitroprusside-type chemistry. The reactivity of five nitrosylpentacyanometallates with the simple reagents previously discussed in chapter one are investigated to show that the nitrosyl group can be positive, neutral or negative and that this information could be easily acquired from the stretching frequency of the nitrosyl group in the infra-red. A value for the nitrosyl stretching frequency is given, above which a compound would be expected to exhibit nitroprusside-type chemistry. These compounds would be expected to be vasodilators.
Thesis, PhD Doctor of Philosophy
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