Inhibition of Hill Reaction by 2-Azido-s-triazine Derivatives: QSAR Study with Molecular Connectivity Indices

This study was undertaken to find a simple and accurate structural parameters for the quantita­ tive description of inhibitory potency of 2-azido-s-triazines in Hill reaction and to gain more information about the mechanism of inhibition on molecular level. A very good correlation (r = 0.946) was obtained between the plS(> values (the negative logarithm of the molar concentra­ tion that causes 50% inhibition) and the valence zero-order and the difference between the second-order and the valence second-order molecular connectivity indices. This m odel, when compared with the empirical models based on the 1-octano/water partition coefficients and the chromatographic retention data, shows superior performance in accuracy and range of applicabili­ ty. In addition, the direct correspondence between molecular structure and above connectivity indices makes it possible to locate structural features responsible for the inhibitory potency of 2-azido-s-triazines in Hill reaction. From our OSAR analysis, the interaction between the chloro­ plast receptor site and 2-azido-s-triazines, which causes inhibition of Hill reaction, is primarily influenced by the size of alkylamino substituents and it accounts for the most variation in the plS(> data. The structural features of secondary importance that control the magnitude of pUo's are the polarity o f alkylamino chains and the degree of branching on alpha carbon atom of R: alkylamino substituent. Compared with the main factor, the size of alkylamino substituents, they can be viewed as a fine tuning elements for the inhibitory potency of 2-azido-s-triazines.