The dynamics and orientation of a lipophilic drug within model membranes determined by 13C solid-state NMR

Chemistry

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https://doi.org/10.1039/b712892d
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Keywords

Carbon Isotopes, Computer Simulation, Dimyristoylphosphatidylcholine, Lipid Bilayers, Magnetic Resonance Spectroscopy, Magnetics, Manganese, Models, Chemical, Molecular Structure, Reference Standards, Rotation, Trifluoperazine, Water

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The dynamics and orientation of a lipophilic drug within model membranes determined by 13C solid-state NMR. / Boland, Martin P; Middleton, David A.
In: Physical Chemistry Chemical Physics, Vol. 10, No. 1, 07.01.2008, p. 178-85.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Bibtex

@article{635259d23ff14dfd87980f8606606b31,

title = "The dynamics and orientation of a lipophilic drug within model membranes determined by 13C solid-state NMR",

abstract = "Methods for determining how a drug interacts with cellular membranes at the molecular level can give valuable insight into the mode of action of the drug and its absorption, distribution and metabolism profile. A procedure is described here to determine the orientation and location of the lipophilic drug trifluoperazine (TFP) intercalated into dimyristoylphosphatidylcholine (DMPC) bilayers, by using a novel combination of high-resolution solid-state nuclear magnetic resonance (SSNMR) methods to observe signals from (13)C within the drug at natural abundance. SSNMR measurements of (1)H-(13)C dipolar couplings for TFP and selective broadening of (13)C NMR peaks by paramagnetic Mn(2+) together suggest a model for the location, orientation and dynamics of the drug within lipid bilayers that offers an explanation for the lysoprotective effect of the drug at low concentrations. The experiments described are straightforward to implement and can be used for the routine analysis of drug-membrane interactions to provide useful information for drug design and structure refinement.",

keywords = "Carbon Isotopes, Computer Simulation, Dimyristoylphosphatidylcholine, Lipid Bilayers, Magnetic Resonance Spectroscopy, Magnetics, Manganese, Models, Chemical, Molecular Structure, Reference Standards, Rotation, Trifluoperazine, Water",

author = "Boland, {Martin P} and Middleton, {David A}",

year = "2008",

month = jan,

day = "7",

doi = "10.1039/b712892d",

language = "English",

volume = "10",

pages = "178--85",

journal = "Physical Chemistry Chemical Physics",

issn = "1463-9076",

publisher = "Royal Society of Chemistry",

number = "1",

}

RIS

TY - JOUR

T1 - The dynamics and orientation of a lipophilic drug within model membranes determined by 13C solid-state NMR

AU - Boland, Martin P

AU - Middleton, David A

PY - 2008/1/7

Y1 - 2008/1/7

N2 - Methods for determining how a drug interacts with cellular membranes at the molecular level can give valuable insight into the mode of action of the drug and its absorption, distribution and metabolism profile. A procedure is described here to determine the orientation and location of the lipophilic drug trifluoperazine (TFP) intercalated into dimyristoylphosphatidylcholine (DMPC) bilayers, by using a novel combination of high-resolution solid-state nuclear magnetic resonance (SSNMR) methods to observe signals from (13)C within the drug at natural abundance. SSNMR measurements of (1)H-(13)C dipolar couplings for TFP and selective broadening of (13)C NMR peaks by paramagnetic Mn(2+) together suggest a model for the location, orientation and dynamics of the drug within lipid bilayers that offers an explanation for the lysoprotective effect of the drug at low concentrations. The experiments described are straightforward to implement and can be used for the routine analysis of drug-membrane interactions to provide useful information for drug design and structure refinement.

AB - Methods for determining how a drug interacts with cellular membranes at the molecular level can give valuable insight into the mode of action of the drug and its absorption, distribution and metabolism profile. A procedure is described here to determine the orientation and location of the lipophilic drug trifluoperazine (TFP) intercalated into dimyristoylphosphatidylcholine (DMPC) bilayers, by using a novel combination of high-resolution solid-state nuclear magnetic resonance (SSNMR) methods to observe signals from (13)C within the drug at natural abundance. SSNMR measurements of (1)H-(13)C dipolar couplings for TFP and selective broadening of (13)C NMR peaks by paramagnetic Mn(2+) together suggest a model for the location, orientation and dynamics of the drug within lipid bilayers that offers an explanation for the lysoprotective effect of the drug at low concentrations. The experiments described are straightforward to implement and can be used for the routine analysis of drug-membrane interactions to provide useful information for drug design and structure refinement.

KW - Carbon Isotopes

KW - Computer Simulation

KW - Dimyristoylphosphatidylcholine

KW - Lipid Bilayers

KW - Magnetic Resonance Spectroscopy

KW - Magnetics

KW - Manganese

KW - Models, Chemical

KW - Molecular Structure

KW - Reference Standards

KW - Rotation

KW - Trifluoperazine

KW - Water

U2 - 10.1039/b712892d

DO - 10.1039/b712892d

M3 - Journal article

C2 - 18075697

VL - 10

SP - 178

EP - 185

JO - Physical Chemistry Chemical Physics

JF - Physical Chemistry Chemical Physics

SN - 1463-9076

IS - 1

ER -

Research

Text available via DOI:

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