A general model for the interaction of foreign molecules with lipid membranes: drugs and anaesthetics

Jørgensen, Kent; Ipsen, John Hjort; Mouritsen, Ole G.; Bennett, D. L.; Zuckermann, Martin J.

doi:10.1016/0005-2736(91)90397-q

Cited by 117 publications

(40 citation statements)

References 28 publications

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“…Unlike for DMPC, DA considerably shifts the phase transition of DMPG toward lower temperatures, but the total molar enthalpy of DMPG transition remains almost unaltered (see Figure 3 for calorimetric curves and Table 3 for relevant parameters of phase transition). Such behavior, a decrease of the phase transition temperature (T m ) accompanied by a very small and negligible variation of enthalpy of transition, suggests that DA interacting with DMPG behaves as an "interstitial impurity", 50 that is, interacts superficially with lipid membranes without penetrating into bilayer hydrocarbon core. Similar behavior has been reported for GABA 38 and a derivative of tyrosine, 51 with more detailed description of DMPC/DMPG vesicles containing lidocaine, an anesthetic with aromatic ring and two amine groups.…”

Section: ■ Discussionmentioning

confidence: 99%

First Experimental Evidence of Dopamine Interactions with Negatively Charged Model Biomembranes

Jodko-Piórecka

Litwinienko

2013

ACS Chem. Neurosci.

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Dopamine is essential for receptor-related signal transduction in mammalian central and peripheral nervous systems. Weak interactions between the neurotransmitter and neuronal membranes have been suggested to modulate synaptic transmission; however, binding forces between dopamine and neuronal membranes have not yet been quantitatively described. Herein, for the first time, we have explained the nature of dopamine interactions with model lipid membranes assembled from neutral 1,2-dimyristoyl-snglycero-3-phosphocholine (DMPC), negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG), and the mixture of these two lipids using isothermal titration calorimetry and differential scanning calorimetry. Dopamine binding to anionic membranes is a thermodynamically favored process with negative enthalpy and positive entropy, quantitatively described by the mole ratio partition coefficient, K. K increases with membrane charge to reach its maximal value, 705.4 ± 60.4 M −1 , for membrane composed from pure DMPG. The contribution of hydrophobic effects to the binding process is expressed by the intrinsic partition coefficient, K 0 . The value of K 0 = 74.7 ± 6.4 M −1 for dopamine/DMPG interactions clearly indicates that hydrophobic effects are 10 times weaker than electrostatic forces in this system. The presence of dopamine decreases the main transition temperature of DMPG, but no similar effect has been observed for DMPC. Basing on these results, we propose a simple electrostatic model of dopamine interactions with anionic membranes with the hydrophobic contribution expressed by K 0 . We suggest that dopamine interacts superficially with phospholipid membranes without penetrating into the bilayer hydrocarbon core. The model is physiologically important, since neuronal membranes contain a large (even 20%) fraction of anionic lipids.

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Section: ■ Discussionmentioning

confidence: 99%

First Experimental Evidence of Dopamine Interactions with Negatively Charged Model Biomembranes

Jodko-Piórecka

Litwinienko

2013

ACS Chem. Neurosci.

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“…2) shows a pretransition peak at about 17 • C, due to the tilting of the hydrophobic chains of the phospholipid, and a transition peak at about 25 • C, characterized by a well defined enthalpy variation ( H), due the passage from an ordered phase (the gel phase) to a disordered phase (the liquid-crystalline phase) (Walde, 2004). Stranger molecules in the phospholipid bilayers of MLV can influence the phase transition changing the temperature (T m ) at which it occurs and/or the H (Jorgensen et al, 1991;Marsh, 1996;Castelli et al, 2007b).…”

Section: Mlv/compounds Interaction Analysismentioning

confidence: 99%

Synthesis of n-squalenoyl cytarabine and evaluation of its affinity with phospholipid bilayers and monolayers

Sarpietro¹,

Ottimo²,

Giuffrida³

et al. 2011

International Journal of Pharmaceutics

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“…In fact, a higher partition coefficient is associated with a higher effect on the transition temperature, the partition coefficients of the compounds being 1.04 (syringic acid), 1.43 (vanillic acid), 1.58 (p-hydroxybenzoic acid) and 1.87 (benzoic acid). As the Log P o/w can be well correlated with the compounds lipophilicity, we can suppose that benzoic acid affects, more than the other acids, the transition temperature due to its higher lipophilicity that permits it to better solubilize inside the phospholipid bilayer, and that syringic acid is the least effective on the thermotropic behaviour of [15], in accord with the temperature depression of melting point for ideal solutions [18,19].…”

Section: Resultsmentioning

confidence: 86%

“…The negligible variation in DH can be explained as an interaction which occurs only between the molecules and the phospholipids without deeply interacting with the acyl chains [15], whereas the DH decrease can be explained with a strong interaction of the compound with the lipid chain which prevents the highly cooperative melting of the lipid tails, making the gel-to-fluid phase transition of the bilayer less endothermic and less cooperative. As a result, the intensity of the calorimetric peak decreases and the peak shape broadens.…”

Section: Resultsmentioning

confidence: 98%

“…where T 8 m is the transition temperature of pure DMPC liposomes and T m is the transition temperature of DMPC liposomes prepared in the presence of compounds at different molar fractions) in function of the molar fraction of compounds present in the aqueous lipid dispersion. If we consider the compound as an impurity dissolved in an ideal 2-D solution, the lowering of the lipid bilayer transition temperature can be easily rationalized in terms of Vant'Hoff decrease of freezing temperature [14,15]. In this hypothesis an almost linear decrease of the bilayer transition temperature with the concentration of the foreign molecule within the bilayer should be observed, while the associated enthalpy should remain constant.…”

Section: Resultsmentioning

confidence: 98%

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Structure influence on biophenols solubility in model biomembranes detected by differential scanning calorimetry

Sarpietro¹,

Caruso²,

Librando³

et al. 2005

Mol. Nutr. Food Res.

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The protective effects of some foods, in particular fruits and vegetables, against cardiovascular disease and cancer are believed to be due to the presence of antioxidant substances such as hydroxyaromatic compounds. The aim of this work was to study (i) the interaction of three biophenols derived from benzoic acid (p-hydroxybenzoic acid, vanillic acid, syringic acid and benzoic acid) with model biomembranes and (ii) their transfer through an aqueous medium to be absorbed into a lipid bilayer, investigating the effect they exert on the thermotropic behaviour of model membranes represented by dimyristoylphosphatidylcholine multilamellar vesicles using differential scanning calorimetry. The compounds, when dispersed in liposomes during their preparation, at pH = 4, were found to modify the gel to liquid crystal phase transition of the lipid vesicles, causing a temperature shift towards lower values. The temperature shift was a function of the concentration of acids in the lipid aqueous dispersions and their lipophilic character. The kinetic experiments of compounds transfer through the aqueous medium and the absorption by the bilayer were performed contacting the antioxidant compounds (at a fixed concentration) and the model membrane at increasing incubation times. These experiments reveal that the transfer of the examined compounds through the aqueous medium and their uptake by bilayer are influenced by the presence of substituents located on the ring, which should consequently modify their lipophilicity.

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A general model for the interaction of foreign molecules with lipid membranes: drugs and anaesthetics

Cited by 117 publications

References 28 publications

First Experimental Evidence of Dopamine Interactions with Negatively Charged Model Biomembranes

First Experimental Evidence of Dopamine Interactions with Negatively Charged Model Biomembranes

Synthesis of n-squalenoyl cytarabine and evaluation of its affinity with phospholipid bilayers and monolayers

Structure influence on biophenols solubility in model biomembranes detected by differential scanning calorimetry

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