On use of the variable connectivity index (1)chi(f) in QSAR: Toxicity of aliphatic ethers

The number of non-hydrogen atoms in a molecule, N, appears as a very good m olecular descriptor for the toxicity of aliphatic ethers, despite the fact that it does not differentiate among isomers. The regression based on N as a descriptor for the toxicity in mice of 21 alkyl ethers was reported to yi eld the regression coefficient r = 0.9751. The simple connectivity index (1 )chi produced for the same data a less satisfactory regression: r = 0.9548. To see if variable connectivity index (1)chi (f) can improve the regressio n characterized by N we examined the same data using the variable connectiv ity index (1)chi (f) as a molecular descriptor. By varying x, y, the variab les that discriminate between carbon and oxygen atoms, we obtained regressi on which approaches in quality the best reported regression using weighted paths as descriptor and which is marginally better than the regression base d on N.