Lipophilicity Profiles of Ampholytes

Abstract

ContentsI. Introduction 3385 A. Significance of Amphoteric Drugs and Biomolecules 3385 B. Partitioning of Amphoteric Drugs: Zwitterions Compared to Ordinary Ampholytes 3386 II. Theoretical Background 3386 A. Acid−Base Equilibria 3386 1. Ordinary Ampholytes 3386 2. Zwitterionic Ampholytes: Microdissociation Equilibria and Micro-pK a 3387 3. Zwitterionic Ampholytes Having a Large Value of K Z 3388 B. Partitioning of Zwitterions 3389 1. General Assumptions for Ionizable Solutes 3389 2. General Assumptions for Zwitterionic Ampholytes 3389 3. Zwitterions Having a Large Value of K Z 3391 III. Relevant Techniques 3391 A. Experimental Techniques 3391 1. Measurements of pK a Values 3391 2. Investigation of Microdissociation Equilibria: Assignment of Micro-pK a and K Z 3391 3. Measurement of Lipophilicity Profiles 3392 B. Computational Techniques 3392 1. Two-Dimensional Fragmental Systems 3392 2. Calculation of Virtual log P Values 3392 IV. Lipophilicity Profiles of Zwitterionic Ampholytes 3392 A. Bell-Shaped Distribution Profiles 3392 1. Zwitterions with a Small K Z 3392 2. Zwitterions with a Large K Z 3394 B. U-Shaped Distribution Profiles 3396 C. Counterion Effects on the Partitioning of Cations and Anions 3397 V. Conclusions 3397 A. Physicochemical Outlook 3397 B. Pharmacokinetic Relevance 3397 VI. Acknowledgments 3398 VII. Glossary 3398 VIII. References 3399

Challenges of Antibacterial Discovery

“…The clog D 7.4 takes charge distribution into account. The lipophilicity (and thus the rate of diffusion) of charged molecules is around 1,000-fold less than that of uncharged molecules (287,366), so their partitioning into the membrane is usually discounted. They can, however, traverse the cytoplasmic membrane, driven by the electrochemical potential (proton motive force [PMF]) of biological membranes (366).…”

Hollow fiber supported ionic liquid membrane microextraction for determination of sulfonamides in environmental water samples by high-performance liquid chromatography

“…Theoretically it is feasible to control the ionizing and non-ionizing forms of SAs by adjusting the pH. In addition, the hydrophobicity of the neutral species is logically greater than that of their corresponding ions [44]. When pH is adjusted to the average of pKa 1 and pKa 2 of SAs, the neutral molecule form is the dominant species [14].…”

Studies on equilibrium of anthranilic acid in aqueous solutions and in two-phase systems: Aromatic solvent–water

“…Pagliara et al stress that both deductive and direct methods are not simultaneously precise and assumption-free, meaning that the results must usually be regarded as mere estimated. However the direct measure of K z by UV spectrometry is a simple method and gives good results under condition the sharp isosbestic point is present [21]. The proper description of amino acid in two-phase systems requires additionally determination of the distribution constant K D of acid, which participates in extraction equilibrium in a molecular form (HR w HR o ) or the extraction constant K ex involved in the extraction equilibrium when ion-pair form with inorganic anion X -undergoes an…”

“…In this study we have determined macroconstant K a1 , K a2 values, isoelectric point pH I , tautomerization constant K z and microconstants k 11 , k 12 , k 21 , k 22 values. The distribution of anthranilic acid in two phase systems water -organic solvents was investigated and distribution constant K D , and dimerization constant K dim values were also determined.…”

“…The presence of these points indicates that the equilibrium between HR o and HR ± forms occurs in these systems moreover, permit to determine the tautomeric constant K z , accurately [21]. These deductions were based on analogy to pyridoxine and on analysis of other related compounds (niflumic acid, nicotinic acid).…”