5. Design Safer Chemicals藉由分子設計概念, 使用各種合成化學 (organic/ inorganic)得到比較安全的化學品。
早期focus: efficacy of chemicals, i.e. 效用好, 成本低; 如今修正為: 必須注重對環境與與健康安全的影響與衝擊 (or 毒性)
Green Chemistry is a source prevention approach;
new chemical structural design safe and efficacious
existing chemicals (toxic) structural redesign safe and efficacious
6. General ApproachesReducing absorption;
Use of toxic mechanism
Use of structural-activity relationship
Use of isosteric replacement
Use of retrometabolic designIdentification of equally efficacious, less toxic chemical substitutes
Elimination of the need for associated toxic substancesACS, 640, 1996
8. Toxic MechanismElectrophilic chemical
substancesElectrophilic metabolites
(from metabolism)Reactions with nucleophiles
With defensive systemReactions with nucleophiles
Of non-defensive cellular
Molecules, DNA, RNA, etc excretion toxicityPath I Path II
10. Use of Structure-Activity Relationship 近年來分子模擬的主要工作; sometimes called structure – property relationship;
From qualitative relationship to quantitative structure activity relationships (QSAR); 後者定量關係之建立可以靠 (i) correlation; or (ii) molecular simulation; 用於發展藥物的技巧
11. Some ExamplesPolyeoxylated nonylphenols: as surfactants/emulsifiers; Glycidyl ethers: as reagents for synthesis;
12. Isosteric Replacements 一個新的定義: isosteres – chemical substances, atoms, or substituents that possess near equal or similar molecular shape and volume, approximately the same distribution of electrons, and which exhibit similar physicochemical properties.範例: 三者皆為液體, 12 & 41 沸點皆為 81oC;
13. Metallized azo dyes:
M= Cr (toxic)
M = Fe 色澤類似, 但不具毒性
14. Other Techniques retrometabolic design: soft drug 觀念, i.e. 該物質很容易被新陳代謝作用轉換掉, e.g. hydrolysis step; 因而毒性降低
Equally useful, less toxic substitutes: 例如 acetoacetate 取代isocyanate in sealant and adhesive; isothiazolones for organotin as antifoulant for ships; 等
Elimination of the need for associated toxic substances: 該物質本身無毒, 但其輸送儲存時會用到毒性物質,e.g. 油漆, 水性比油性好, no or less VOC;
15. Designing Biodegradable Chemicals p.157-171, ACS 640, 1996;
Microbial degradation is the major loss mechanism for most organic chemicals;
一般會增加生物分解阻力者: (a) 含鹵素, esp. Cl, F; (b) 太多支鏈, branched, such as quaternary C or tertiary N; (c) nitro-, nitroso- azo- arylamino groups; (d) polycyclic residues, 尤其是超過三個以上; (e) aliphatic ether bonds, C-O-C;
生物法合成的東西大概都可以被生物分解;
16. Biodegradable Chemicals (2) 比較喜歡: 引入oxygen in the form of hydroxyl, aldehydic, carboxylic; unsubstituted linear alkyl chains (>4) and phenyl rings; TPBS: tetrapropylene akylbenzene sulfonate;
LAS: linear alkylbenzene sulfonate
後者比前者容易被生物分解 (一般用途: 清潔劑)
17. 前: Ethoxylated ethanaminium quaternary ammonium salt
後: ester analog of previous compound; 比較容易為生物分解