scholarly journals Quantitative Explanation of Basic Compound Retention Mechanisms in Reversed-Phase Mode Liquid Chromatography

Separations ◽  
2020 ◽  
Vol 7 (4) ◽  
pp. 61
Author(s):  
Toshihiko Hanai
Keyword(s):  
Electron Transfer ◽  
Hydrogen Bonding ◽  
Reversed Phase ◽  
Silica Gels ◽  
Chromatographic Behavior ◽  
Electron Localization ◽  
Interaction Site ◽  
The Difference ◽  
Acidic Compounds ◽  
Quantitative Explanation

The quantitative analysis of the chromatographic behavior of basic compounds measured with pentyl-, hexenyl-, and octyl-bonded silica gels were analyzed in silico employing model phases. The main retention force was the van der Waals (VW) interaction, and the main desorption force was an electrostatic (ES) interaction. The contribution of hydrogen bonding (HB) was weak compared to that for acidic compounds. The quantitative explanation was achieved utilizing the calculated VW, HB, and ES energy values obtained from a molecular mechanics program. The electron localization was observed at the molecular interaction-site calculated MOPAC program. This fundamental approach was like that of explaining chemical reactions. The difference was electron localization in chromatography or electron transfer in a chemical reaction.

scholarly journals Quantitative Explanation of Basic Compound Retention Mechanisms in Reversed-Phase Mode Liquid Chromatography

2020 ◽  
Author(s):  
Toshihiko Hanai
Keyword(s):  
Liquid Chromatography ◽  
In Silico ◽  
Reversed Phase ◽  
Silica Gels ◽  
Chromatographic Behavior ◽  
Electron Localization ◽  
Interaction Site ◽  
The Difference ◽  
Acidic Compounds ◽  
Quantitative Explanation

Abstract: The quantitative analysis of the chromatographic behavior of basic compounds was performed in silico. The liquid chromatography (LC) data measured with pentyl-, hexenyl-, and octyl-bonded silica gels were analyzed in silico employing model phases. The main retention force was the van der Waals (VW) interaction, and the main desorption force was an electrostatic (ES) interaction. The contribution of hydrogen bonding (HB) was weak compared to that for acidic compounds. The quantitative explanation was achieved utilizing the calculated VW, HB, and ES energy values obtained from a molecular mechanics program. The electron localization was observed at the molecular interaction-site calculated MOPAC program. This fundamental approach was like that of explaining chemical reactions. The difference was electron localization in chromatography or electron transfer in a chemical reaction.

Quantitative Explanation of Retention Mechanisms in Reversed-phase Mode Liquid Chromatography, and Utilization of Typical Reversed-phase Liquid Chromatography for Drug Discovery

2019 ◽  
Vol 6 (1) ◽  
pp. 52-64 ◽  
Author(s):  
Toshihiko Hanai
Keyword(s):  
Liquid Chromatography ◽  
Drug Discovery ◽  
In Silico ◽  
Reversed Phase ◽  
Chromatographic Behavior ◽  
Log P ◽  
Reversed Phase Liquid Chromatography ◽  
Retention Mechanisms ◽  
Phase Liquid ◽  
Quantitative Explanation

The retention mechanism in reversed-phase liquid chromatography was quantitatively described using log P (octanol-water partition coefficient). The hydrophobic (lipophilic) interaction liquid chromatography was then used to measure the hydrophobicity of a variety of compounds. Furthermore, the technique has been used as an analytical method to determine molecular properties during the drug discovery process. However, log P values cannot be applied to other chromatographic techniques. Therefore, the direct calculation of molecular interactions was proposed to describe the general retention mechanisms in chromatography. The retention mechanisms in reversed-phase liquid chromatography were quantitatively described in silico by using simple model compounds and phases. The competitive interactions between a bonded-phase and a solvent phase clearly demonstrated the retention mechanisms in reversed-phase liquid chromatography. Chromatographic behavior of acidic drugs on a pentyl-, an octyl-, and a hexenyl-phase was quantitatively described in the in silico analysis. Their retention was based on their hydrophobicity, and hydrogen bonding and electrostatic interaction were selectivity of the hexenyl-phase. This review focuses on the quantitative explanation of the retention mechanisms in reversed-phase liquid chromatography and the practical applications in drug discovery.

Development and Validation of Spectrophotometric and Liquid Chromatographic Methods for Estimation of Tigecycline in Injections

2020 ◽  
Vol 13 (5) ◽  
pp. 5148-5154
Author(s):  
Sagar Suman Panda ◽  
Ravi Kumar B.V.V.
Keyword(s):  
Area Under The Curve ◽  
Reversed Phase ◽  
Equal Concentration ◽  
Pharmaceutical Dosage Form ◽  
Liquid Chromatographic Method ◽  
Array Detection ◽  
The Difference ◽  
The One ◽  
Development And Validation ◽  
Liquid Chromatographic

Three new analytical methods were optimized and validated for the estimation of tigecycline (TGN) in its injection formulation. A difference UV spectroscopic, an area under the curve (AUC), and an ultrafast liquid chromatographic (UFLC) method were optimized for this purpose. The difference spectrophotometric method relied on the measurement of amplitude when equal concentration solutions of TGN in HCl are scanned against TGN in NaOH as reference. The measurements were done at 340 nm (maxima) and 410nm (minima). Further, the AUC under both the maxima and minima were measured at 335-345nm and 405-415nm, respectively. The liquid chromatographic method utilized a reversed-phase column (150mm×4.6mm, 5µm) with a mobile phase of methanol: 0.01M KH2PO4 buffer pH 3.5 (using orthophosphoric acid) in the ratio 80:20 %, v/v. The flow rate was 1.0ml/min, and diode array detection was done at 349nm. TGN eluted at 1.656min. All the methods were validated for linearity, precision, accuracy, stability, and robustness. The developed methods produced validation results within the satisfactory limits of ICH guidance. Further, these methods were applied to estimate the amount of TGN present in commercial lyophilized injection formulations, and the results were compared using the One-Way ANOVA test. Overall, the methods are rapid, simple, and reliable for routine quality control of TGN in the bulk and pharmaceutical dosage form. 

scholarly journals Predicting Pharmacokinetic Properties of Potential Anticancer Agents via Their Chromatographic Behavior on Different Reversed Phase Materials

2021 ◽  
Vol 22 (8) ◽  
pp. 4257
Author(s):  
Małgorzata Janicka ◽  
Anna Mycka ◽  
Małgorzata Sztanke ◽  
Krzysztof Sztanke
Keyword(s):  
Liquid Chromatography ◽  
Anticancer Agents ◽  
Skin Permeation ◽  
Reversed Phase ◽  
Chromatographic Behavior ◽  
Chromatographic Retention ◽  
Quantitative Structure ◽  
Animal Testing ◽  
Structure Activity ◽  
Pharmacokinetic Properties

The Quantitative Structure-Activity Relationship (QSAR) methodology was used to predict biological properties, i.e., the blood–brain distribution (log BB), fraction unbounded in the brain (fu,brain), water-skin permeation (log Kp), binding to human plasma proteins (log Ka,HSA), and intestinal permeability (Caco-2), for three classes of fused azaisocytosine-containing congeners that were considered and tested as promising drug candidates. The compounds were characterized by lipophilic, structural, and electronic descriptors, i.e., chromatographic retention, topological polar surface area, polarizability, and molecular weight. Different reversed-phase liquid chromatography techniques were used to determine the chromatographic lipophilicity of the compounds that were tested, i.e., micellar liquid chromatography (MLC) with the ODS-2 column and polyoxyethylene lauryl ether (Brij 35) as the effluent component, an immobilized artificial membrane (IAM) chromatography with phosphatidylcholine column (IAM.PC.DD2) and chromatography with end-capped octadecylsilyl (ODS) column using aqueous solutions of acetonitrile as the mobile phases. Using multiple linear regression, we derived the statistically significant quantitative structure-activity relationships. All these QSAR equations were validated and were found to be very good. The investigations highlight the significance and possibilities of liquid chromatographic techniques with three different reversed-phase materials and QSARs methods in predicting the pharmacokinetic properties of our important organic compounds and reducing unethical animal testing.

scholarly journals Theoretical Study of the Structures of 4-(2,3,5,6-Tetrafluoropyridyl)Diphenylphosphine Oxide and Tris(Pentafluorophenyl)Phosphine Oxide: Why Does the Crystal Structure of (Tetrafluoropyridyl)Diphenylphosphine Oxide Have Two Different P=O Bond Lengths?

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2778
Author(s):  
Joseph R. Lane ◽  
Graham C. Saunders
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonding ◽  
Phosphine Oxide ◽  
Density Functional ◽  
Lone Pair ◽  
Diphenylphosphine Oxide ◽  
Functional Theory ◽  
Weak Hydrogen Bonding ◽  
Independent Molecules ◽  
The Difference

The crystal structure of 4-(2,3,5,6-tetrafluoropyridyl)diphenylphosphine oxide (1) contains two independent molecules in the asymmetric unit. Although the molecules are virtually identical in all other aspects, the P=O bond distances differ by ca. 0.02 Å. In contrast, although tris(pentafluorophenyl)phosphine oxide (2) has a similar crystal structure, the P=O bond distances of the two independent molecules are identical. To investigate the reason for the difference, a density functional theory study was undertaken. Both structures comprise chains of molecules. The attraction between molecules of 1, which comprises lone pair–π, weak hydrogen bonding and C–H∙∙∙arene interactions, has energies of 70 and 71 kJ mol−1. The attraction between molecules of 2 comprises two lone pair–π interactions, and has energies of 99 and 100 kJ mol−1. There is weak hydrogen bonding between molecules of adjacent chains involving the oxygen atom of 1. For one molecule, this interaction is with a symmetry independent molecule, whereas for the other, it also occurs with a symmetry related molecule. This provides a reason for the difference in P=O distance. This interaction is not possible for 2, and so there is no difference between the P=O distances of 2.

scholarly journals Temperature Effects on Retention and Separation of PAHs in Reversed-Phase Liquid Chromatography Using Columns Packed with Fully Porous and Core-Shell Particles

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Christophe Waterlot ◽  
Anaïs Goulas
Keyword(s):  
Limit Of Detection ◽  
Tap Water ◽  
Reversed Phase ◽  
Chromatographic Behavior ◽  
Core Shell ◽  
Reversed Phase Liquid Chromatography ◽  
Porous Particles ◽  
Phase Liquid ◽  
Effects Of Temperature ◽  
Shell Particles

Effects of temperature on the reversed-phase chromatographic behavior of PAHs were investigated on three columns. The first was the recent C18column (250 mm × 4.6 mm) packed with 5 µm core-shell particles while the others were more conventional C18columns (250 mm × 4.6 mm) packed with fully porous particles. Among the 16 PAHs studied, special attention has been paid to two pairs of PAHs, fluorene/acenaphthene and chrysene/benzo[a]anthracene, which often present coeluting problems. Due to the low surface area of the core-shell particles, lowest retention time of each PAH was highlighted and effects of the temperature on the separation of PAHs were negligible in regard to those using columns packed with fully porous particles. For each PAH studied, it was demonstrated that peaks were symmetrical and may be considered as Gaussian peaks when the column packed with core-shell particle was employed. In the best condition, the separation of PAHs was conducted at 16°C under very low pressure values (670–950 psi = 46–65 bars). Depending on PAHs, the limit of detection ranged from 0.88 to 9.16 μg L−1. Analysis of spiked acetonitrile samples with PAHs at 10 and 50 µg L−1and tap water at 10 µg L−1gave very good recoveries (94%–109.3%) and high precision (1.1%–3.5%).

scholarly journals Flavones’ and Flavonols’ Antiradical Structure–Activity Relationship—A Quantum Chemical Study

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 461 ◽  
Author(s):  
Maciej Spiegel ◽  
Tadeusz Andruniów ◽  
Zbigniew Sroka
Keyword(s):  
Electron Transfer ◽  
Hydrogen Bonding ◽  
Density Functional ◽  
Hydrogen Abstraction ◽  
Quantum Chemical Study ◽  
Hydrogen Atom Transfer ◽  
Hydroxyl Group ◽  
Water Solvent ◽  
Intramolecular Hydrogen ◽  
Catechol Moiety

Flavonoids are known for their antiradical capacity, and this ability is strongly structure-dependent. In this research, the activity of flavones and flavonols in a water solvent was studied with the density functional theory methods. These included examination of flavonoids’ molecular and radical structures with natural bonding orbitals analysis, spin density analysis and frontier molecular orbitals theory. Calculations of determinants were performed: specific, for the three possible mechanisms of action—hydrogen atom transfer (HAT), electron transfer–proton transfer (ETPT) and sequential proton loss electron transfer (SPLET); and the unspecific—reorganization enthalpy (RE) and hydrogen abstraction enthalpy (HAE). Intramolecular hydrogen bonding, catechol moiety activity and the probability of electron density swap between rings were all established. Hydrogen bonding seems to be much more important than the conjugation effect, because some structures tends to form more intramolecular hydrogen bonds instead of being completely planar. The very first hydrogen abstraction mechanism in a water solvent is SPLET, and the most privileged abstraction site, indicated by HAE, can be associated with the C3 hydroxyl group of flavonols and C4’ hydroxyl group of flavones. For the catechol moiety, an intramolecular reorganization to an o-benzoquinone-like structure occurs, and the ETPT is favored as the second abstraction mechanism.

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