nternal considerations- Prevention of toxic eifects 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 atoxic structure through the norma/ metabo/sm(新除代 of the organism or strategic molecular relocation of the toxic groups C. structural blocking of toxic groups d. alternate molecular sites for toxic groups
❖ 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 (新陈代谢) of the organism or strategic molecular relocation of the toxic groups; c. structural blocking of toxic groups; d. alternate molecular sites for toxic groups. Internal considerations-Prevention of toxic effects
ternal considierations-Prevention of toxic eifects ☆ Indirect biotoxicati0m-山 Activat0mn 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 (代谢物) Bioactivation represents a characteristic mechanism or the toxicity of many carcinogenic(致癌的 mutagen(诱变的), and teratogenic(畸胎的 chemicals
❖ 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 （代谢物）. ❖ 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
nternal considerations- Prevention of toxic eifects C Avoidance ofindirect biotoxication [bioactivation 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 modificationsthat prevent bioactivation
❖ C. Avoidance of indirect biotoxication (bioactivation) ❖ 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 Internal considerations-Prevention of toxic effects
Opportunities for the synthetic chemist o 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 %s The opportunities and approaches are expanded further by the possibility of factoring more than one approach into the molecular design ss e.g. both properties that reduce exposure and ghe or more properties that facilitate excretion(排浙r metabolic(代谢) deactivation
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 （排泄） or metabolic （代谢）deactivation
Opportunities for the synthetic chemist The effective harmonization(一致) of the safety considerations and of complex living organisms with the efficacy considerations of chemical structures for industrial and commercial purposes is expected to achieve Delicate(精巧的) balance between safety and efficacy s Data and information on the structure-biologica activity relationship of these same chemicals'at molecular level
❖ The effective harmonization（一致） of the safety considerations and of complex living organisms with the efficacy considerations of chemical structures for industrial and commercial purposes is expected to achieve. ❖ Delicate（精巧的） balance between safety and efficacy. ❖ Data and information on the structure-biological activity relationship of these same chemicals at molecular level. Opportunities for the synthetic chemist