Structure-toxicity analyses of Tetrahymena pyriformis exposed to pyridines – an examination into extension of surface-response domains was written by Seward, J. R.;Cronin, M. T. D.;Schultz, T. W.. And the article was included in SAR and QSAR in Environmental Research in 2001.COA of Formula: C6H6N2O3 This article mentions the following:
A selection of mechanistically diverse substituted pyridines were tested in the Tetrahymena pyriformis population growth impairment assay. The response-surface approach was used to derive multiple-regression type structure-toxicity relationships between T. pyriformis population growth impairment toxicity data (log (IGC50-1)) and the 1-octanol/water partition coefficient (log Kow) and one of two different descriptors of MO interaction: energy of the LUMO (ELUMO) and maximum acceptor superdelocalizability (SMAX). A statistically robust model (log (IGC50-1) = -3.91+0.50 (log Kow) + 10.70(SMAX); n = 83, r2 = 0.756, s = 0.38, F = 124, Pr > F = 0.0001) was developed with SMAX as the indicator of reactivity. This model was not statistically different in fit from the model (log (IGC50-1) = -1.19+0.56 (log Kow) – 0.61 (ELUMO); n = 86, r2 = 0.749, s = 0.38, F = 124, Pr > F = 0.0001) derived using the alternative descriptor of electrophilic interaction. Compounds with high residual values were removed. An examination of these outliers from both response-surfaces, revealed that pyridines substituted in the 2-position with electron-releasing groups and halogenated nitro-substituted pyridines did not fit the above models well. A third group of outliers, the mono-halogenated pyridines, was unique to the SMAX response-surface, which are neutral narcotics with potentially high volatility. A comparison of observed and predicted toxicities for a validation set of pyridines for the SMAX surface (log (observed IGC50-1) = 0.10+0.75 (log (predicted IGC50-1)); n = 10, r2 = 0.662, s = 0.49, F = 15.7, Pr > F = 0.004) and the ELUMO surface (log (observed IGC50-1) = 0.17+0.80 (log (predicted IGC50-1)); n = 10, r2 = 0.707, s = 0.45, F = 19.3, Pr > F = 0.002) validated the above models, with the fit in the same range as the parent model. The model derived with SMAX was compared to the response-surface derived for substituted benzenes (log (IGC50-1) = -3.47+0.50 (log Kow) + 9.85(SMAX); n = 197, r2 = 0.816, s = 0.34, F = 429, Pr > F = 0.0001) revealing the similarities in slope and intercept between the two response-surfaces. The model fit was poorer for the pyridine surface, which may be a factor of increased reactivity due to the presence of nitrogen and the associated pair of unshared electrons in the ring not present in benzene. However, the similarity of the pyridine and benzene response-surfaces suggests that the domain defined for benzenes may be extended to encompass nitrogen heterocyclic pyridines. In the experiment, the researchers used many compounds, for example, 3-Hydroxy-6-methyl-2-nitropyridine (cas: 15128-90-2COA of Formula: C6H6N2O3).
3-Hydroxy-6-methyl-2-nitropyridine (cas: 15128-90-2) belongs to pyridine derivatives. The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital. The lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the σ bonds. One of the examples of pyridines is the well-known alkaloid lithoprimidine, which is an A3 adenosine receptor antagonist and N,N-dimethylaminopyridine (DMAP) analog, commonly used in organic synthesis.COA of Formula: C6H6N2O3