RELATION OF STRUCTURE AND ANTIBACTERIAL ACTIVITY 169 



mide acts as an anion, cation or neutral molecule, so long as the structure of the 

 compound permits a separation of charge, with the formation of a quininoid 

 structure by movement of bonds after ionization of the amino group. The essence 

 of the polarity in this connection is the electropositivity of the NHj group. 



The general form of the sulphonaniides is H2N-C6H4S02-NH-R. If the substituent R 

 {e.g., a thiazole or a pj-ridine ring compound) is an electron acceptor, the negative charge 

 on the 1SO2 increases, and the positive charge on the NHj becomes greater. Substitutions 

 in otlier parts of the 7>-aminobenzene sulphonamide molecule that interfere with the 

 induction of this positive charge will produce inactive compounds (see also Jensen and 

 Schmith 1942). 



The conception of activity in terms of the highly polar amino grouji is supported 

 by the work of Bradbury and Jordan (1942), who found that sulphanilamide, sulpha- 

 thiazole, sulphapyridine and ^>aminobenzoic acid all modified the electrophoretic mobility 

 of Bad. coli in the same wPoV. Inactive benzene ring compounds and non-resonating 

 isomers of the active compounds did not produce the characteristic change in mobility. 

 As the result of testing a large number of derivatives and analogues of yj-aminobenzoic 

 acid, Johnson, Green and Pauli (1944) confirmed the importance of the amino group in 

 the para position and concluded that inhibitory activity may be determined primarily 

 by the chemical reactivity of the functional group rather than by structural similarity 

 of the substance to ;p-aminobenzoic acid. 



In conclusion, it should be noted that though sulphonamides like sulphathiazole 

 and sulphadiazine approach the maximum attainable activity in vitro as judged 

 by their physicochemical characters, they are not necessarily the best attainable 

 for chemotherapy, which must take into consideration absorption, excretion and 

 toxicity in the host, as well as susceptibility to antagonism by products of the 

 host's metabolism. 



The Relation of Chemical and Antitacterial Activity in other Compounds. 



It will be clear from the foregoing that though within a group of chemically 

 related compounds activity and chemical structure are closely connected, no 

 ready generaUzations in this respect about antibacterial substances are possible 

 in the present state of our knowledge. There are, however, certain noteworthy 

 features which widely different types of compounds, whether antiseptic or chemo- 

 therapeutic, have in common. It is beyond the scope of this book to deal with 

 them in detail. The student is referred to the paper by Albert (1942), upon which 

 we have drawn in the following paragraphs. 



We are not for the moment concerned with antiseptics which act by an immediate 

 and extensive disruption of the economy of the bacterial cell, such as we see in 

 the coagulative antiseptics. Apart from these, antibacterial substances range 

 from the frank antiseptics that are general protoplasmic poisons, to the highly 

 selective chemotherapeutic agents, with all grades of selectivity of action in 

 between. 



The life of the cell depends on the smooth working together of many systems 

 and any agent that interferes with this will be an antiseptic. Since all the enzymes 

 about which there is chemical information have proved to be proteins, it is not 

 surprising that agents affecting all proteins are normally antiseptics. Oxidizing 

 agents, halogens and formaldehyde fall into this category. Their mode of action 

 on a protein is seldom understood, but this is a general problem of protein chemistry 

 rather than specifically the concern of bacteriology. Agents that upset the relations 

 of lipins and proteins to one another will kill the cell, for it is on these relations 



