Influence of chlorine substituents on biological activity of chemicals

A number of well known polychlorinated chemicals are toxicologically and en vironmentally unsafe. Because of their persistence they are in the focus of public discussions against chlorine chemistry. However, chlorinated organi c chemicals in the molecular weight range between 200 and 600 constitute an important and indispensable segment in the arsenal of existing biologicall y active chemicals used as pharmaceuticals or crop protection agents. Over the course of time it has been found empirically that the introduction of a chlorine atom into one or more specific positions of a biologically active molecule may substantially improve the intrinsic biological activity. In s ome cases the presence of a chlorine atom is even crucial for significant a ctivity of a compound derived from nature or chemical synthesis like in the diverse compounds 1 to 12 and 23 to 30. But in other cases chlorination di minishes or abolishes biological activity as shown for the chlordane homolo gues 139 to 143. Thus a chlorine atom, like any other substituent, is a mod ulator of activity as represented in the many examples 31 to 124. Almost al l non-reactive chlorinated chemicals and chlorine-free chemicals are devoid of any biological activity at the highest concentration typically used in primary screening tests for discovery of useful biological properties. The influence of a substituent such as chlorine on the biological activity of a potential drug or crop protection agent still has to be established empiri cally in biological experiments designed to detect desired activity or toxi cological properties. Sometimes chlorine does prove to be the optimum for i mprovement of activity. Long-term rigorous investigations of several hundre d chlorinated compounds, registered by the authorities as pharmaceutical dr ugs or crop protection agents, show that the generalisation ("all chlorinat ed chemicals as a rule are dangerous"), deduced from the negative toxicolog ical properties of a hundred chlorinated and reactive compounds of low mole cular weight that are relevant in terms of safe working conditions in the c hemical industry and for ecological safety, is not justified. Chlorinated c ompounds are not generally toxic or dangerous. Highly reactive chemicals or polychlorinated compounds can not be compared with regard to toxicological properties with unreactive compounds having a low degree of chlorination. The chlorine atom, as one of many possible substituents used in synthetic o rganic chemistry, will remain in the future one of the important tools for probing structure-activity relationships in life science research and as a molecular component in commercialised compounds, in order to provide safer, more selective and more environmentally compatible products with higher ac tivity for medicine and agriculture.