Analysis of counterions

A quantitative analysis of counterion localization in a salt-free solution of star-like PEs is carried out on the basis of an exact numerical solution of the corresponding Poisson-Boltzmann (PB) problem (Sect. 5). Here, the conformational degrees of freedom of the flexible branches are accounted for within the Scheutjens-Fleer self-consistent field (SF-SCF) framework. The latter is used to prove and to quantify the applicability of the concept of colloidal charge renormalization to PE stars, that exemplify soft charged colloidal objects. The predictions of analytical and numerical SCF-PB theories are complemented by results of Monte Carlo (MC) and molecular dynamics (MD) simulations. The available experimental data on solution properties of PE star polymers are discussed in the light of theoretical predictions (Sect. 6). 

A quantitative analysis of counterion localization in a salt-free solution of star-like PEs is described in [29, 37]. Radial distributions for both the electrostatic potential and the density of counterions were obtained by a numerical solution of the corresponding PB problem within a cell model. The conformational degrees of freedom of the branches of a central star were accounted for within the SF-SCF method [120]. Due to the computational efficiency, the SF-SCF framework allows for a systematic study of a many-armed star with sufficiently long arms in a large cell. The range of the parameters that could be covered by the SF-SCF method exceeds that of contemporary MD and MC simulations. 

In pharmaceutical development, the determination of APIs and counterions are two important assays. Due to the charge and/or hydrophobicity differences, APIs and counterions are usually analyzed by different chromatographic techniques that require different separator columns and/or detection methods. For example, reversed-phase liquid chromatography is most commonly used for analyzing APIs with intermediate to higher hydrophobicity, but it fails to provide adequate retention for hydrophilic counterions. In contrast, ion chromatography provides a selective and highly sensitive solution for the analysis of counterions. 

The thermodynamic analysis of the selectivity of ion exchange with the participation of ions of quaternary ammonium bases [56--58] has shown that an increase in bonding selectivity, when metal ions are replaced by organic ions, which is usually accompanied by an increase in entropy of the system (Table 5). It follows from Table 5 that a drastic increase in bonding selectivity upon passing to a triethylbenzylammonium counterion (the most complex ion) is due to a considerable increase in the entropy of the system. 

An analysis of the hydration structure of water molecules in the major and minor grooves in B-DNA has shown that there is a filament of water molecules connecting both the inter and the intra phosphate groups of the two strands of B-DNA. However, such a connectivity is absent in the case of Z-DNA confirming earlier MC simulation results. The probability density distributions of the counterions around DNA shows deep penetration of the counterions in Z-DNA compared to B-DNA. Further, these distributions suggest very limited mobility for the counterions and show well defined counter-ion pattern as originally suggested in the MC study. 

In the case of Kryptofix 221D, a cryptand able to complex the alkali metal cations [141-143], it has been observed that it is solubilized mainly in the palisade layer of the AOT-reversed micelles. And from an analysis of the enthalpy of transfer of this solubilizate from the organic to the micellar phase it has been established that the driving force of the solubilization is the complexation of the sodium counterion. In addition, the enthalpy... 

However, X-ray analysis of these salts reveals the overall ratio of the acceptor to donor to vary (depending on the counterion and halide) from 4 1 to 1 1 (Table 3), and they show halide anions in close contact with two to four acceptor moieties, as illustrated in Fig. 10. 

For 10-fold 13C labelled retinal, it has been shown that the differences between chemical shifts for polyene chain carbons of the chromophore in its native environment and detergent-solubilised system were small67 Analysis of the environment of the Schiff base has supported the model of stabilisation based on the protonation by a complex counterion. Three factors were responsible for the excessive positive charge in polyene (i) electronegative nitrogen, (ii) protonation and (iii) counterion strength. 

Shi et al.71 have assigned the backbone and side-chain chemical shifts for 103 of 238 residues of proteorhodopsin using solid state NMR spectroscopy. Analysis of the chemical shifts has allowed determination of protonation states of several carboxylic acids as well as boundaries and distortions of trans-membrane a-helices and secondary structure elements in the loops. It has been shown that internal Asp227, making a part of the counterion, is ionised, while Glul42 located close to the extracellular surface is neutral. 

FIGURE 9.4 Analysis of cold medicine formulations containing active ingredients, impurities, and counterions. (Courtesy of Waters Corp.)... 

This chapter reviews the imderlying principles of ion chromatography and its applications in pharmaceutical analysis. An overview of eluent systems, applications of gradients, electrolytic eluent generation, suppressors and stationary phases is provided. Application of ion chromatography to the confirmation of counterions, active ingredient analysis, competitive analysis and development work are discussed. 

Another major ion chromatography application is the analysis of active ingredient counterions. Frequently, drug substances are formulated as salts in order to achieve specific pharmaceutical properties (such as improved solubility or control of dissolution rate). The analysis of... 

Another ion chromatography pharmaceutical application is the analysis of amines and amphoteric compounds such as choline (see Figure 19). Such compounds may be present either as counterions, as mentioned above, or as synthesis by-products. In either case, ion chromatography can be advantageously utilized for this class of compounds due to the limited utility of gas chromatography and the lack of a UV chromophore for such compounds. Again, screening for such compounds in pharmaceutical preparations can be best accomplished... 

The use of capillary electrophoresis (CE) during the synthetic drug development is described from the preclinical development phase to the final marketed stage. The chapter comprises the determination of physicochemical properties, such as acid—base dissociation constants (pKJ, octanol—water distribution coefficients (logP), and analysis of pharmaceutical counterions and functional excipients. 

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