Chromatography computational chemical

Normal-phase liquid chromatography is thus a steric-selective separation method. The molecular properties of steric isomers are not easily obtained and the molecular properties of optical isomers estimated by computational chemical calculation are the same. Therefore, the development of prediction methods for retention times in normal-phase liquid chromatography is difficult compared with reversed-phase liquid chromatography, where the hydrophobicity of the molecule is the predominant determinant of retention differences. When the molecular structure is known, the separation conditions in normal-phase LC can be estimated from Table 1.1, and from the solvent selectivity. A small-scale thin-layer liquid chromatographic separation is often a good tool to find a suitable eluent. When a silica gel column is used, the formation of a monolayer of water on the surface of the silica gel is an important technique. A water-saturated very non-polar solvent should be used as the base solvent, such as water-saturated w-hexane or isooctane. 

A quantitative analysis of the structure-retention relationship can be derived by using the relative solubility of solutes in water. One parameter is the partition coefficient, log P, of the analyte measured as the octanol-water partition distribution. In early work, reversed-phase liquid chromatography was used to measure log P values for drug design. Log P values were later used to predict the retention times in reversed-phase liquid chromatography.The calculation of the molecular properties can be performed with the aid of computational chemical calculations. In this chapter, examples of these quantitative structure-retention relationships are described. 

The agreement between the observed and predicted k values of aromatic acids was within 10%. The correlation coefficient was 0.954 (n = 32). An error of greater than 10% for 3-hydroxy-2-naphthoic acid and 2-hydroxybenzoic acid was attributed mainly to an error in their K.A values.25 The partition coefficient, logP, and dissociation constant, pKA, of analytes can be obtained by simple calculations and by computational chemical calculations, and thus the retention time can be predicted in reversed-phase liquid chromatography. 

Hanai T. Simulation of chromatography of phenolic compounds with a computational chemical method. J Chromatogr A 2004, 20 Feb 1027(l-2) 279-287. 

In special cases, polar gases such as ammonia, formic acid and water are doped into the carrier gas to improve the analyte s solubility in the carrier gas. In both supercritical fluid and liquid chromatography, the analyte solubility in the carrier liquid affects the retention time. The carrier liquid is called the eluent and/or the mobile phase. The prediction of retention times in liquid chromatography is very difficult due to the lack of a solubility prediction method. However, the retention can be predicted by computational chemical methods using model phases. ... 

General computational chemical analysis of liquid chromatographic retention is performed without solvents in the calculation. Generally, mixed solvents with and without pH-controlled ions are present as the eluent components in liquid chromatography. At present, these solvent systems cannot be handled by computational chemical calculations. The measurement of direct interactions, however, reveals the different strengths of molecular interactions between an analyte and the packing material surface. The difference in molecular interaction energy values can be used as a relative retention time. 

T. Hanai, K. Koizumi, T. Kinoshita, R. Arora and F. Ahmed, Prediction of pKa values of phenolic and nitrogen-containing compounds by computational chemical analysis compared to those measured by liquid chromatography,/. Chromatogr., A, 1997, 762, 55-61. 

T. Hanai, R. Miyazaki, A. Koseki and T. Kinoshita, Computational chemical analysis of the retention of acidic drugs on a pentyl-bonded silica gel in reversed-phase liquid chromatography,/. Chramatagr. Set, 2004, 42, 354-360. 

T. Hanai, H. Hatano, N. Nimura and T. Kinoshita, Computational chemical analysis of chiral recognition in liquid chromatography, selectivity of iV-(R)-l-(a-naphthyl)ethylaminocarbonyl-(R or 5 )-valine and N-(5 )-l-(ot-naphthyl)ethylaminocarbonyl-(R or 5 )-valine bonded amino-propyl silica gels. Anal Chim. Acta, 1996, 332, 213-224. 

T. Hanai, Computational chemical analysis of enantiomer separations of derivatized amino acids in reversed-phase liquid chromatography, Internet Electron.]. Mol. Des., 2004, 3, 379-386. 

T. Hanai, log nK Chromatography and computational chemical analysis for drug discovery, Curr. Med. Chem., 2005, 12, 501-525. 

T. Hanai, Y. Inoue, T. Sakai and H. Kumagai, Computational chemical analysis of the highly sensitive detection of bromate in ion chromatography,/. Chem. Inf. Comput. Set, 1998, 38, 885-888. 

T. Hanai, Simulation chromatography of phenolic compounds using a computational chemical method,/. Chromatogr., A, 2003,1027,279-287. 

T. Hanai, K. Koizumi and T. Kinoshita, Prediction of retention factors of phenolic and nitrogen-containing compounds in reversed-phase liquid chromatography based on log P and pKa obtained by computational chemical calculation,/. Liq. Chromatogr. Relat. TechnoL, 2000,23, 363-385. 

T. Hanai, Computational chemical analysis of the molecular recognition of graphitic carbon, presented at the 21st International Symposium on Capillary Chromatography and Electrophoresis, Park City, 1999. 

The above results indicate that mimic ion-exchange liquid chromatography is feasible compared to using an immobilized-HSA column. The computational chemical analysis of molecular interactions using the mimic ion exchanger is practical for the rapid screening of drug candidates. 

The analytical method described here can predict the relative sensitivity detected by chemiluminescence reactions using luminol, and computational chemical analysis can help to predict sensitive detection in liquid chromatography. The reaction mechanisms of other compounds under similar conditions should be the same as those described for the above compounds. Further computational chemical study will clarify the reaction mechanisms of chemiluminescence and their sensitivity differences. 

---