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The first conformer-specific experimental partition coefficients are presented for octanol/water, the most widespread solvent system to predict lipophilicity of drugs. Rotamer populations in octanol and water were elucidated from ¹H NMR vicinal coupling constants and were combined with classical partition coefficients to obtain the conformer-specific ones. Feasibility of the determination of conformer-specific partition coefficients is exemplified on amphetamine and clenbuterol, two flexible drug molecules. Partition capacities of the amphetamine rotamers have been proven to be essentially equal. The conformers of clenbuterol, however, have been found to be greatly different in partition properties, which could be interpreted in terms of intramolecular interactions between the vicinal polar sites and the solvent-accessibility of the groups. The conformers could be put into order of their membrane-influx and -outflow propensities. Deviations between experimental and calculated log P values could also be interpreted in view of the species-specific partition coefficients.

The rate constants and the activation parameters for the exchange between water solvent and [U(H2O)10]⁴⁺ and [UF(H2O)9]³⁺, and a lower limit for the rate constant at room temperature for [Th(H2O)10]⁴⁺, were determined by ¹⁷O NMR spectroscopy in the temperature range 255−305 K. The experiments were made at different constant hydrogen ion concentrations, which varied between 0.16 and 0.8 mol kg^-1. The Th(IV) system was investigated using Tb³⁺ as a shift reagent. The following kinetic parameters at 25 °C were obtained:  kex = (5.4 ± 0.6) 10⁶ s ^-1, ΔH^&thermod; = 34 ± 3 kJ mol^-1, ΔS^&thermod; = −16 ± 10 J mol^-1 K^-1 for U⁴⁺(aq), kex = (5.5 ± 0.7) 10⁶ s ^-1, ΔH^&thermod; = 36 ± 4 kJ mol^-1, ΔS^&thermod; = 3 ± 15 J mol^-1 K^-1 for UF³⁺(aq), and kex > 5 10⁷ s ^-1 for Th⁴⁺(aq), where the uncertainty is given at the 2σ-level. This is the first experimental information on the kinetic parameters for the exchange of water for any M⁴⁺ ion. There is no information on the rates and mechanisms of ligand substitutions involving other mono-dentate ligands, hence the mechanistic interpretation of the data is by necessity provisional. The kinetic data and the known ground-state geometry with a coordination number of 10 ± 1 for the Th(IV) and U(IV) complexes suggest a dissociatively activated interchange mechanism. There is no noticeable effect of coordination of one fluoride or one hydroxide to U(IV) on the water exchange rate. This is unusual, for other metal ions there is a strong labilizing of coordinated water when a second ligand is bonded, e.g., in complexes of aluminum and some d-transition elements. In previous studies of the rates and mechanisms of ligand exchange in uranium(VI) systems we found a strong decrease in the lability of coordinated water in some fluoride containing complexes.