Phosphinylidene compounds R(1)R(2)P(O)H are important functionalities in organophosphorus chemistry and display prototropic tautomerism. Quantifying the tautomerization rate is paramount to understanding these compounds' tautomerization behavior, which may impact their reactivities in various reactions. We report a combined theoretical and experimental study of the initial tautomerization rate of a range of phosphinylidene compounds. Initial tautomerization rates are found to decrease in the order H3PO2 > Ph2P(O)H > (PhO)2P(O)H > PhP(O) (OAlk)H > AlkP(O)(OAlk)H ≈ (AlkO)2P(O)H, where "Alk" denotes an alkyl substituent. The combination of computational investigations with experimental validation establishes a quantitative measure for the reactivity of various phosphorus compounds, as well as an accurate predictive tool.

Fluoroquinolones are an important therapeutic class in the targeting of new and resistant bacterial infections. Fluoroquinolones bind to bacterial type II topoisomerase via a water-Mg 21 bridge.However, binding to magnesium-containing molecules outside of the target cells increases the minimum inhibitory concentration (MIC) and promotes drug resistance. As a result, fluoroquinolones are counter-indicated with magnesium and multivalent metal cation containing drugs, such as antacids. The antibiotic efficacy of fluoroquinolones has also been shown to be pH dependent, as we show the effect of protonation state on magnesium binding. This work presents a systematic computational study of fluoroquinolones' magnesium-binding properties. We use B3LYP density functional theory and triple-zeta basis sets, to evaluate Mg H 2 O ð Þ 21 N binding affinities. Complexation is predicted to be thermodynamically favorable at neutral and basic compared to acidic pH. The calculated complexation energies broadly capture experimental binding affinities, suggesting this is a valid approach for designing new fluoroquinolones with a target magnesium binding affinity. We also investigate the effect of chemical substitution at the carboxylic acid to help in the identification of potential new antibiotics based on the fluoroquinolone pharmacophore. K E Y W O R D S binding affinity, computational, fluoroquinolones, metal complexes 1 | I N T R O D U C T I O N Fluoroquinolones are a class of broad spectrum antibiotic drugs based on the general quinolone pharmacophore, fluorinated at carbon R 6 (Figure 1). FIG URE 1 Essential fluoroquinolone structure Int J Quantum Chem. 2017;117:e25428.