Internal considerations-Prevention of toxic effects 2. Facilitation of biodegradation a. oxidation b reduction C hydrolysis 四大学化学学院 2002年7月26日 16
四川大学化学学院 2002年7月26日 16 Internal considerations-Prevention of toxic effects ◼ 2. Facilitation of biodegradation ◼ a. oxidation ◼ b. reduction ◼ c. hydrolysis
Internal considerations -Prevention of toxic effects B. Avoidance of direct toxication 1. Selection of non -toxic chemical classes or parent compounds 2. Selection of non-toxic functional groups a avoidance of toxic groups b planned biochemical elimination of toxic structure through the normal metabolism of the organism or strategic molecular relocation of the toxic group C structural blocking of toxic groups d. alternative molecular sites for toxic 四大g是9耻pS 2002年7月26日 17
四川大学化学学院 2002年7月26日 17 Internal considerations-Prevention of toxic effects ◼ B. Avoidance of direct toxication ◼ 1. Selection of non-toxic chemical classes or parent compounds ◼ 2. Selection of non-toxic functional groups ◼ a. avoidance of toxic groups ◼ b. planned biochemical elimination of toxic structure through the normal metabolism of the organism or strategic molecular relocation of the toxic group ◼ c. structural blocking of toxic groups ◼ d. alternative molecular sites for toxic groups
Internal considerations-Prevention of toxic effects Indirect biotoxication - bioactivation It describes the circumstances where a chemical is not toxic in its original structural form but becomes toxic after in vivo transformation to a toxic metabolite Bioactivation represents a characteristic mechanism for the toxicity of many carcinogenic (致癌的, mutagenic(诱变 的), and teratogenic(畸胎的) chemicals 四大学化学学院 2002年7月26日
四川大学化学学院 2002年7月26日 18 Internal considerations-Prevention of toxic effects ◼ Indirect biotoxication—bioactivation ◼ It describes the circumstances where a chemical is not toxic in its original structural form but becomes toxic after in vivo transformation to a toxic metabolite. ◼ Bioactivation represents a characteristic mechanism for the toxicity of many carcinogenic(致癌的), mutagenic（诱变 的）, and teratogenic（畸胎的） chemicals
Internal considerations-Prevention of toxic effects C. Avoidance of indirect biotoxication (bioactivation) I. Avoiding chemicals with known activation routes a highly electrophilic or nucleophilic groups b unsaturated bonds c. other structural features 2. Structural blocking of bioactivation.2 Incorporation of structural modifications that prevent bioactivation 四大学化学学院 2002年7月26日 19
四川大学化学学院 2002年7月26日 19 Internal considerations-Prevention of toxic effects ◼ C. Avoidance of indirect biotoxication (bioactiovation) ◼ 1. Avoiding chemicals with known activation routes ◼ a. highly electrophilic or nucleophilic groups ◼ b. unsaturated bonds ◼ c. other structural features ◼ 2. Structural blocking of bioactivation ◼ Incorporation of structural modifications that prevent bioactivation
Opportunities for the synthetic chemist Both the external and internal considerations provide a wide range of opportunities and approaches to the synthetic chemist for designing chemical structures that reduce or eliminate the toxicity of industrial and commercial chemicals The opportunities and approaches are expanded further by the possibility of factoring more than one approach into the molecular design e.g. both properties that reduce exposure and 3ge one or more properties that facilitate excretion or metabolic deactivation 四大学化学学院 2002年7月26日
四川大学化学学院 2002年7月26日 20 Opportunities for the synthetic chemist ◼ Both the external and internal considerations provide ◼ a wide range of opportunities and approaches to the synthetic chemist for designing chemical structures that reduce or eliminate the toxicity of industrial and commercial chemicals. ◼ The opportunities and approaches are expanded further by the possibility of factoring more than one approach into the molecular design. ◼ e.g. both properties that reduce exposure and one or more properties that facilitate excretion or metabolic deactivation