Isosteric Substitution in the Design of Safer Commercial Chemicals

Isosteric Substitution in the Design of Safer Commercial Chemicals 

The application of isosterism for the design of safer commercial chemicals is much less common than it is for the design of safer drugs or pesticides. There are some examples, however, of how isosterism has been used to design safer commercial chemical substances. One very successful application is in the case of metallized azo dyes [82, 83]. Historically, chromium was a metal of choice in many metallized azo dyes because it imparts the desired color and fastness. Hexavalent chromium (Cr6+) was often used in making such dyes. 

Hexavalent chromium is a known human carcinogen, however, and its commercial use is strictly regulated and highly discouraged by environmental authorities. An alternative metal to chromium in premetallized azo dyes would have to have the same color and fastness properties as chromium but without the toxicity. It has been found that iron, which is essentially nontoxic, often imparts the same desirable qualities as chromium when used in azo dyes [82,83]. This is exemplified in comparing azo dyes 44 and 45. Dyestuff 45 has the same color and fastness as 44, but does not contain chromium. Other examples of dyestuffs that use iron rather than chromium are available [82, 83]. 

Azo dyes made from 47, and also their cleavage products from azo reduction, are appreciably less genotoxic than the corresponding benzidine-based dyes. An example is the mutagenic (and carcinogenic) benzidine-based dye Direct Violet 43 (48) and its corresponding isosteric analog (49), in which the benzidine moiety is replaced with 47. Other examples are available [84]. 

48 2 and 2 X = C Direct Violet 43. Mutagenic, known human carcinogen. 

---