Reference sets RS1 to RS6 are the most fundamental reference datasets consisting generally of carbon, hydrogen and one other element (except for RS1 which includes only aliphatic and aromatic hydrocar-bons). RS2 introduces a number of common nitrogen environments such as tertiary (3 ○ ) amines, imines, nitriles, and azo-groups. It is worth pointing out that the definitions used here for many of the functionals groups, such as amines and imines, are determined based on the atoms they are bonded to and irrespective of whether the atom appears in an aromatic ring. This broadly encompasses other common functional groups within these definitions, including many different classes of heteroaromatic systems which may be considered distinctly different by an organic chemist. Common oxygen environments such as ethers, aldehydes, ketones, and esters are considered in RS3. RS4 and RS5 extend into chlorinated and fluorinated hydrocarbon systems, respectively, where the halogen atom is substituted onto either an aromatic or methyl carbon atom. Finally, RS6 incorporates various sulphur environments, including thioethers, disulfides, and thiocarbonyls. The remaining reference sets in the non-hydrogen bonding reference datasets (RS7-RS23) include combinations of the functional groups found in RS2-RS6. Some additional functional groups are also introduced such as nitro-groups which first appear in RS7, as well as sulphoxides and sulphones which first appear in RS14.