Observations on the biopharmaceutical importance of chain length in chemically related compounds

The physicial properties of compounds which have a common parent structure, and differ only by the sequential addition of a methylene group to an alkyl side chain might be expected to demonstrate a linear variation in behaviour as a function of the length of the alkyl carbon chain. Although this is indeed so in many instances, there are many examples in the literature in which a break in the pattern of the behaviour of the product is observed at a chain length of five carbons (±1). In this paper, examples are highlighted in which this is true for solid-state properties (melting point, wettability), solubility, liquid properties, partition and biological response. NMR data demonstrate that certain substituent alkyl chains are essentially rigid until a chain length of 5 carbons is exceeded, after which the freedom of movement is increased; this is used as a basis to explain the observed behaviour