Proton ionizable

Source J. J. Christensen, L. D. Hansen, and R. M. Izatt, Handbook of Proton Ionization Heats and Related Thermodynamic... 

We do not discuss in detail the cases of tautomerism of heterocycles embedded in supramolecular structures, such as crown ethers, cryptands, and heterophanes, because such tautomerism is similar in most aspects to that displayed by the analogous monocyclic heterocycles. We concentrate here on modifications that can be induced by the macrocyclic cavity. Tire so-called proton-ionizable crown ethers have been discussed in several comprehensive reviews by Bradshaw et al. [90H665 96CSC(1)35 97ACR338, 97JIP221J. Tire compounds considered include tautomerizable compounds such as 4(5)-substituted imidazoles 1///4//-1,2,4-triazoles 3-hydroxy-pyridines and 4-pyridones. 

The high-energy cosmic radiation, which consists of energy-rich protons, ionizes neutral atoms and molecules as it passes through the cosmos, for example, as follows ... 

Handbook of Proton Ionization Heats and Related Thermodynamic Qunatities" Wiley Interscience, New York, 1976. 

Veith, H.J. Alkali Ion Addition in FD Mass Spectrometry. Cationization and Protonation-Ionization Methods in the Application of Nonactivated Emitters. Tetrahedron 1977, 33, 2825-2828. 

Christensen, J.J., Hansen, L.D., and Izatt, R.M. Handbook of Proton Ionization Heats (NewYork John Wiley Sons. 1975), 269 p. 

Nitroprusside reacts with hydroxide to yield the corresponding nitro complex. The rate is first order in both reactants and probably involves nucleophilic attack by OH on the NO followed by proton ionization. Infrared studies on 0-labeled compounds indicate the NOJ to be bound as nitro (-NO2) rather than as nitrito (-ONO) [3, 116]. 

Porphyrin Axial ligation E°, V versus NHE Proton ionization References... 

Scheme 5.2 outlines our design of nucleophilic transacylation catalysts based on crown-complexed alkaline-earth metal ions. By virtue of the acidity-enhancing effect ofthe complexed metal ion, dissociation ofthe proton-ionizable function XH should take place under moderately basic conditions. The metal ion assists acyl transfer from a reactant ester to the catalyst and its subsequent transfer from the acylated catalyst to an external nucleophile (solvent), thus restoring the active form of the... 

Ignoring any ionization in the side chain R it can be seen from the data in Table 1 that all amino acids undergo two reversible proton ionizations steps (equation 1). Consequently, depending upon the solution pH, the amino acids can coordinate through either or both of the amino (NH2) or carboxyl (C02 ) groups in aqueous media. In addition those with polar R groups, e.g. Asp, Cys, His, Glu, Pen, offer additional coordinating sites. 

Table 10 The Nucleic Bases, Their Proton Ionization Constants (pit,), and the Nomenclature of Their Nucleoside and Nucleotide Derivatives...

Fid. 25. Kinetic mechanisms for nucleotide binding including proton ionization steps, (a) Proposed mechanism for the initial interaction of RNase with 3 -UMP. PH is the monoanionic nucleotide, and P is the dianionic nucleotide. The horizontal arrows represent the kinetically significant steps in the pH range 4.5-7.0 (free protons are not indicated on the diagram), (b) Proposed mechanism for the isomerization of enzyme 3 -UMP complexes. Reproduced from del Rosario and Hammes (470). 

Kinetic analyses allowed the experimental results to be related to the dependence of transport rates and selectivities on carrier properties [6.9, 6.17, 6.18]. Detailed studies of 8 and 9 in vesicles bore on the efficiency, the selectivity and the mechanism of the processes [6.19]. The rates of transport by proton ionizable macrocyclic carriers are pH dependent [6.12]. Diverse other ligands have been used as carriers, such as acyclic polyethers or calixarene derivatives [6.20, A.6]. 

The effect of urinary pH on drug ionization also has toxicological implications. For example, in cases of phenobarbital (a weak acid barbiturate) overdose the urine can be alkalinized (the pH elevated) by administering sodium bicarbonate to the patient. The resultant increase in pH shifts the dissociation equilibrium for this weak acid to the right, producing an increase in the proportion of the ionized form, less reabsorption in the kidneys, and more rapid elimination. Conversely, acidifying the urine with ammonium chloride will increase the excretion rate of drugs that are weak bases since they will be more protonated (ionized) and less reabsorbed (more polar, less lipophilic). 

Molecules can have more than one pKa depending on the number of ionizable centers. In pharmaceutical research the ionization state between pH 2 (stomach) and 8 (pH in colon) is most interesting. A review by Taylor covers the effects of the different protonization/ionization forms of a molecule on pharmacokinetic and pharmacodynamic properties. Molecules are less soluble in aqueous media but more permeable through membranes in their neutral form. 

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