Revisionist look at solvophobic driving forces in reversed-phase liquid chromatography

Carr, Peter W.; Li, Jianjun; Dallas, Andrew J.; Eikens, David I.; Tan, Lay Choo

doi:10.1016/0021-9673(93)80800-n

Cited by 114 publications

(86 citation statements)

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“…This finding is consistent with the conclusion of Carr et al that bulk hexadecane is a good model for the bonded phase for nonpolar solutes but not for polar solutes though the solutes and methanol range tested in their work are different from ours. 27) Our results are also similar to those of Tsukahara et al who compared dodecane/MeOH-water (M40, M60, M80 and M100) partitioning coefficients, P D/M-W , of typical small organic compounds with the corresponding retention factor, k, measured on an ODS column. 28) By using their data for non-amphiprotic benzene derivatives (PhX with Xϭalkyls, halogens, OEt, Ac, CN, CO 2 R and NO 2 ), we plotted log k values 28) against log P oct 29) at each methanol concentration, yielding the best correlation at M40, log k M40 , (rϭ0.982).…”

Section: Resultssupporting

confidence: 80%

Hydrophobicity Parameters Determined by Reversed-Phase Liquid Chromatography. XV: Optimal Conditions for Prediction of log Poct by Using RP-HPLC Procedures.

Yamagami

Kawase

Iwaki

2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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Recently, in connection with the remarkable development of computational technologies for rational drug designs, the necessity has become apparent of rapid measurement or estimation of molecular properties of chemicals having a potential for medical use. In particular, hydrophobicity (as expressed by the logarithm of 1-octanol/water partition coefficient, log P oct ) is identified as one of the most important properties that govern potencies; its prediction has attracted much attention from medicinal chemists, agrochemists and many investigators in various fields such as pharmacology, toxicology, environmental chemistry and food chemistry. 1,2)Instead of measuring log P oct by the standard but time-consuming shake-flask method, reversed-phase chromatography (RP-HPLC) has increasingly been used as a powerful tool to predict log P oct from the readily accessible retention factor, log k, (given by kϭ(t R Ϫt 0 )/t 0 where t 0 and t R express elution times of the non-retained substance and sample, respectively).Extensive studies have been made to establish an optimal RP-HPLC system providing a good linearity between log P oct and log k.3-10) Many workers have used an ODS-type column with methanol-water mobile phases to obtain a normalized parameter, log k W (k W : the retention factor extrapolated to 0% organic modifier), as an alternative to log P oct . 3,5,8) In our experience, this log k W approach works well for non-polar solutes but tends to provide overestimated log P oct values for strong H-acceptors. [10][11][12][13][14][15] From systematic studies of log k obtained under various HPLC conditions for typical heteroaromatic compounds such as (di)azines, furans and thiophenes, we were led to the conclusion that the use of an eluent containing around 50% methanol, which usually provides a more direct correlation with log P oct , is the most convenient and practical procedure for rapid estimation of log P oct provided H-donors (amphiprotic compounds) are treated separately.11-15) Our results so far obtained are illustrated graphically in Fig. 1. This conclusion has been derived from the following results.First, we have shown that, for each series of monosubstituted (di)azines, log P oct can be excellently correlated with log k in different compositions of methanol-water eluents by a general formula Eq. 1 containing two terms correcting for H-bonding effects: 16) log kϭalog P oct ϩrs I ϩsS HA ϩconst.( 1) where the s I parameter represents the Charton's inductive electronic substituent constant, 17) and S HA designates the substituent H-acceptor scale that we have recently defined where the value of S HA is set at unity for H (the unsubstituted * To whom correspondence should be addressed. The use of log k derived from reversed phase (RP)-HPLC retention times provides a convenient method for estimating log P oct values (P oct : 1-octanol/water partition coefficient). In order to establish optimal HPLC conditions, the difference between chromatographic (C18 modified column and aqueous methanol eluents) and bulk solve...

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Section: Resultssupporting

confidence: 80%

Hydrophobicity Parameters Determined by Reversed-Phase Liquid Chromatography. XV: Optimal Conditions for Prediction of log Poct by Using RP-HPLC Procedures.

Yamagami

Kawase

Iwaki

2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…6. As we can see, there is a fairly good linear relationship for each compound, which indicates the validity of a linear Van't Hoff type equation as shown below: (1) which is derived from the fundamental equation: (2) by assuming that ΔH° and ΔS°, the standard enthalpy and entropy change for solute transfer from mobile phase to stationary phase respectively, are independent of temperature. This is usually true over a narrow range of temperature.…”

Section: 13mentioning

confidence: 99%

“…However, the separation of analytes as extremely hydrophilic as the above compounds by conventional RPLC which is after all based on hydrophobic, that is highly lipophilic interaction processes [1][2][3][4][5][6], is not easy. Such analytes are usually not sufficiently retained to be well separated due to their high hydrophilicity.…”

Section: Introductionmentioning

confidence: 99%

Application of silica-based hyper-crosslinked sulfonate-modified reversed stationary phases for separating highly hydrophilic basic compounds

Luo

Paek

et al. 2008

Journal of Chromatography A

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The separation and determination of hydrophilic basic compounds are of great importance in many fields including clinical and biological research, pharmaceutical development and forensic analysis. However, the most widely used analytical separation technique in these disciplines, reversed-phase liquid chromatography (RPLC), usually does not provide sufficient retention for several of the important classes of highly hydrophilic basic compounds including catecholamines, many drug metabolites and many drugs of abuse. Commonly eluents having little or no organic modifier and/ or strong ion pairing agents must be used to achieve sufficient retention and separation. Use of highly aqueous eluents can lead to column failure by dewetting, resulting in poor retention, selectivity, reproducibility and slow recovery of performance. The use of a strong ion pairing agent to increase retention renders the separation incompatible with mass spectrometric detection and complicates preparative separations. This paper describes the successful applications of a novel type of silica-based, hyper-crosslinked, sulfonate-modified reversed stationary phase, denoted as − SO 3 -HC-C 8 -L, for the separation of highly hydrophilic cations and related compounds by a hydrophobically assisted cation-exchange mechanism. Compared to conventional reversed-phases, the − SO 3 -HC-C 8 -L phase showed significantly improved retention and separation selectivity. Concurrently, due to the presence of both cation-exchange and reversed-phase retention mechanisms and the high acid stability of hypercrosslinked phases, the separation can be optimized by changing the type or concentration of ionic additive or organic modifier, and by varying the column temperature. In addition, gradients generated by programming the concentration of either the ionic additive or the organic modifier can be applied to reduce the analysis time without compromising resolution. Furthermore, remarkably different chromatographic selectivities, especially toward cationic solutes, were observed upon comparison of the − SO 3 -HC-C 8 -L phase with conventional reversed-phases. We believe that the combination of these two types of stationary phases will be very useful in two-dimensional liquid chromatography.

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“…Another very popular theory is the lipophilic theory of Carr and co-workers [7]. According to this theory, favorable interactions between the solute and the stationary phase drive transfer from mobile to the stationary phase.…”

Section: Introductionmentioning

confidence: 99%

“…This theory is based on a thermodynamic cycle and views the retention in RPLC as association in vacuo between the elute and the stationary phase and subsequent transfer of the participating species into the mobile phase [8,9]. This model has been considered very useful at predicting trends in retention upon changes in mobile phase composition and in altering certain molecular properties of the solute, principally its size [7]. However, it underestimates effects of cavity formation in the stationary phase [10,11] and it does not take into account possible solute-stationary phase interactions or the experimentally supported fact that retention depends on the nature of the bonded chain phase [12].…”

Section: Introductionmentioning

confidence: 99%

Reverse-High Performance Liquid Chromatography Mechanism Explained by Polarization of Stationary Phase

Andrade-Eiroa¹

2011

CheM

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Original results and conclusions on Reverse Phase High Performance Liquid Chromatography (RPLC) mechanism are here presented. So far, none of the theoretical approaches applied to the RPLC mechanism can explain the retention and elution mechanisms of most of the analytes by RPLC, especially neutral organic compounds. Our experiences allowed us to state that RPLC retention mechanism most likely occurs through polarization of stationary phase (usually dielectric surfaces) submerged into solvents with huge dielectric constant and high dipole moment (i.e. water and/or acetonitrile) at high pressures as those applied in RPLC systems. The surface polarized interacts with polarizable target analytes (i.e. naphthalene, pyrene or benzo(ghi)perylene) in such a way that the retention depends on the medium polarizability of the target compound. The higher is the medium polarizability of the compound retained the higher is its retention time.By using Polycyclic Aromatic Hydro-carbons (PAHs) and 6-nitrochrysene as probes, we found that although the dependence of retention times on pressure is not evident in most cases, the interaction between pressure and the mobile phase dipole moment is evidenced at the light of the constructed mathematical models. Two very different cases can be distinguished:1. On one hand, when low dipole moment mobile phases are used, high pressure means big work developed by the system in such a way that high pressures inside the system reduce retention times compared to low pressures.2. On the another one, when high dipole moment solvents are used as mobile phase, high pressure entails an outstanding increase of the retention times compared to low dipole moment mobile phases. This is most likely due to high pressures that entail closer alignment of mobile phase dipoles and lesser tilt of them, originating an outstanding electric field inside the analytical column.In addition to this, reduced retention times for dipole solutes (6-nitrochrysene, dipole molecule) compared to non-polar solutes (PAHs) were observed when pressure drops. This conclusions would allow to extend the model to basic/acid molecules at different pH. In this case, electrostatic repulsions among analyte molecules should be considered.

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Revisionist look at solvophobic driving forces in reversed-phase liquid chromatography

Cited by 114 publications

References 50 publications

Hydrophobicity Parameters Determined by Reversed-Phase Liquid Chromatography. XV: Optimal Conditions for Prediction of log Poct by Using RP-HPLC Procedures.

Hydrophobicity Parameters Determined by Reversed-Phase Liquid Chromatography. XV: Optimal Conditions for Prediction of log Poct by Using RP-HPLC Procedures.

Application of silica-based hyper-crosslinked sulfonate-modified reversed stationary phases for separating highly hydrophilic basic compounds

Reverse-High Performance Liquid Chromatography Mechanism Explained by Polarization of Stationary Phase

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