The conformation-dependent lipophilicity of morphine glucuronides as calculated from their molecular lipophilicity potential
The lipophilicity of conformers of morphine-3-O-glucuronide (M3G) and morphine-6-O-glucuronide (M6G) was calculated by the molecular lipophilicity potential method (MLP) in order to quantify the “chameleonic” behavior (hydrophilic in water, lipophilic in lipidic media) of these compounds.
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Cited by (64)
Population, basicity and partition of short-lived conformers. Characterization of baclofen and pregabalin, the biaxial, doubly rotating drug molecules
2018, European Journal of Pharmaceutical SciencesCitation Excerpt :Vistoli et al. have also shown that molecular flexibility is related to lipophilicity of compounds (Vistoli et al., 2009). Forerunners in this field have also shown how conformer-specific lipophilicities can be determined using theoretical calculations (Gaillard et al., 1994), and why the bulk physico-chemical parameters must be viewed in light of the dynamic behavior of the molecules. In this work our aim was to determine the conformer-specific parameters (populations, protonation constants, lipophilicities) of baclofen and pregabalin drugs around two rotational axes (Fig. 1).
Advances in microspeciation of drugs and biomolecules: Species-specific concentrations, acid-base properties and related parameters
2016, Journal of Pharmaceutical and Biomedical AnalysisCitation Excerpt :These results dispel the still wide-spread notion that the lipophilicity of ionic, and especially zwitterionic species is insignificant compared to the non-charged form. Zwitterionic compounds with unexpectedly high lipophilicity include morphine-6-glucuronide [93], where the existence of conformers with intramolecular hydrogen bonds was proposed to interpret the increased apparent lipophilicity in a lipid-like environment [94]. The effect of conformational changes on lipophilicity have long been assumed [95], but remained at the theoretical level.
Separation of substrates and closely related glucuronide metabolites using various chromatographic modes
2016, Journal of Chromatography ACitation Excerpt :In a polar environment like the mobile phase employed in RPLC, they exist as extended conformers to make their polar groups more accessible to the water. With high proportion of ACN in HILIC, the polar groups are masked by intramolecular H-bonding, leading to folded conformations that are more lipophilic [64]. In RPLC, morphine-3-glucuronide was less retained than morphine-6-glucuronide, which could be expected since their respective log D values were estimated to −4.15 and −1.92, respectively.
Drug delivery: A process governed by species-specific lipophilicities
2014, European Journal of Pharmaceutical SciencesCitation Excerpt :Our method for experimentally quantifying the lipophilicity of microspecies can be extended to other compounds of medicinal interest. Zwitterionic compounds with unexpectedly high lipophilicity include morphine-6-glucoronide (Stain et al., 1995), where a hypothesis has been proposed for the existence of conformers with intramolecular hydrogen bonds displaying increased apparent lipophilicity in a lipid-like environment (Gaillard et al., 1995). The sedating side-effects of certain zwitterionic antihistamines, like acrivastine and cetirizine (Mann et al., 2000), could also be explained by quantifying the lipophilicity of the zwitterionic species.
Lipophilicity of zwitterions and related species: A new insight
2011, European Journal of Pharmaceutical SciencesCitation Excerpt :Our method for experimentally quantifying the lipophilicity difference between the non-charged and zwitterionic microspecies can be extended to other compounds of medicinal interest, such studies are in progress in our department. Zwitterionic compounds with unexpectedly high lipophilicity include morphine-6-glucoronide (Stain et al., 1995), where a hypothesis has been proposed for the existence of conformers with intramolecular hydrogen bonds displaying increased apparent lipophilicity in a lipid-like environment (Gaillard et al., 1995). The sedating side-effects of certain zwitterionic antihistamines, like acrivastine and cetirizine (Mann et al., 2000), could also be explained by quantifying the lipophilicity of the zwitterionic species.
Alternative measures of lipophilicity: From octanol-water partitioning to IAM retention
2008, Journal of Pharmaceutical Sciences