This study introduces the second release of the Tool for the Automatic Analysis of Lexical Sophistication (TAALES 2.0), a freely available and easy-to-use text analysis tool. TAALES 2.0 is housed on a user's hard drive (allowing for secure data processing) and is available on most operating systems (Windows, Mac, and Linux). TAALES 2.0 adds 316 indices to the original tool. These indices are related to word frequency, word range, n-gram frequency, n-gram range, n-gram strength of association, contextual distinctiveness, word recognition norms, semantic network, and word neighbors. In this study, we validated TAALES 2.0 by investigating whether its indices could be used to model both holistic scores of lexical proficiency in free writes and word choice scores in narrative essays. The results indicated that the TAALES 2.0 indices could be used to explain 58% of the variance in lexical proficiency scores and 32% of the variance in word-choice scores. Newly added TAALES 2.0 indices, including those related to n-gram association strength, word neighborhood, and word recognition norms, featured heavily in these predictor models, suggesting that TAALES 2.0 represents a substantial upgrade.

The new potentiometric method was shown to be reliable for determining the solubility-pH profiles of uncharged ionizable drug substances. Its speed compared to conventional equilibrium measurements, its sound theoretical basis, its ability to generate the full solubility-pH profile from a single titration, and its dynamic range (currently estimated to be seven orders of magnitude) make the new pH-metric method an attractive addition to traditional approaches used by preformulation and development scientists. It may be useful even to discovery scientists in critical decision situations (such as calibrating computational prediction methods).

Quantitative structure-activity relationships have been found among macrolide antibacterial agents in their potencies against the bacterial pathogen Pasteurella multocida both in vitro and in mouse infections. To obtain these relationships we measured, among other things, the pK(a)'s and log P's of 15 known macrolides of diverse structures. Among these compounds, in vitro potency [log(1/MIC)] is a function of log P, log D, and CMR (R = 0.86). In vivo potency is a function of the higher pK(a), the HPLC chromatographic capacity factor log k', log(1/MIC) and pNF (R = 0.93). pNF is defined as the negative logarithm of the fraction of neutral drug molecules present in aqueous solution at pH 7.4. The same physical properties were determined for 14 macrolides not used in developing the original QSAR models. Using the in vivo model, we calculated the mouse protection potency ranges for these new compounds. Ten estimates agreed with those observed, three were lower by a half-order of magnitude, and one was calculated to be active in the range of 15-50 mg/kg, but in fact was not active at 50 mg/kg, the highest level tested. When these new compounds were combined with the original 15, and the QSAR's updated, the new equations for the in vitro and in vivo potencies were essentially the same as those originally found. Hence, the physical properties indicated above are major determinants of macrolide antibacterial potencies.

Partial atomic charges are significant descriptors in predicting the water solubilities of crystalline organic compounds from their chemical structures. Lipophilicity remains the predominant factor. It was also found that quantitative estimates of hydrogen bond strengths (hydrogen bond factors) play important roles. These descriptors can be easily interpreted to guide chemists to the synthesis of compounds with increased or decreased water solubility. This work is based on a set of 22 compounds the aqueous solubilities of which were determined by a new potentiometric method, pSOL, and were confirmed, in part, by the traditional shake-flask method. A new software package, HYBOTPLUS, furnished the partial atomic charges and hydrogen bond factors.

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