Anesthetic-membrane interaction: A 2H nuclear magnetic resonance study of the binding of specifically deuterated tetracaine and procaine to phosphatidylcholine

1984 ◽  
Vol 62 (2-3) ◽  
pp. 178-184 ◽  
Author(s):  
Eric C. Kelusky ◽  
Ian C. P. Smith
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Local Anesthetics ◽  
Nuclear Magnetic Resonance Study ◽  
Weakly Bound ◽  
Slow Exchange ◽  
H Nmr ◽  
Line Shapes ◽  
Acyl Chains ◽  
Nuclear Magnetic

The binding of the local anesthetics tetracaine and procaine with multilamellar dispersions of egg phosphatidylcholine has been studied by 2H nuclear magnetic resonance (NMR). The 2H-NMR line shapes of specifically deuterated local anesthetics are found to be very dependent on the attainment of a true equilibrium. The equilibrium could be most properly reached by the use of repeated freeze–thaw–vortex cycles. The data for tetracaine are consistent with the three-site exchange model proposed earlier. Tetracaine is in slow exchange between a strongly bound site and a weakly bound site and in fast exchange between the weakly bound site and free in solution. The slow exchange rate is estimated, from temperature and dilution studies, to be approximately 1.5 × 103 s−1 at pH 5.5 and slightly faster at pH 9.5. Comparisons of the quadrupole splittings with those seen for our earlier work in egg phosphatidylethanolamine suggest that the location of the strongly bound site in phosphatidylcholine is dependent on the anesthetic charge. This is in contrast to egg phosphatidylethanolamine, where molecular shapes appear to be the determining factor for the location of the anesthetic. Procaine bound very weakly to the model membranes, to yield only a broad resonance and no quadrupole splitting. It appears that procaine, unlike tetracaine, is not bound by the ordered acyl chains.

α-N,N-Dimethylaminoethylferrocene. A nuclear magnetic resonance study relating to stereoselective metalation

1986 ◽  
Vol 64 (4) ◽  
pp. 667-669 ◽  
Author(s):  
Ian R. Butler ◽  
William R. Cullen ◽  
F. Geoffrey Herring ◽  
N. R. Jagannathan
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Spatial Correlation ◽  
Nuclear Magnetic Resonance Study ◽  
Magnetic Resonance Study ◽  
H Nmr ◽  
Nmr Study ◽  
Nuclear Magnetic

A 1H nmr study of Fe(C5H4CHMeNMe2-η)(C5H4PPh2-η), 2, using the nOe difference experiment, shows a spatial correlation between the —NMe2 group and the site of stereoselective lithiation.

An optical stopped-flow and 1H and 113Cd nuclear magnetic resonance study of the kinetics and stoichiometry of the interaction of the lanthanide Yb3+ with carp parvalbumin

1983 ◽  
Vol 61 (8) ◽  
pp. 860-867 ◽  
Author(s):  
David C. Corson ◽  
Lana Lee ◽  
Gerard A. McQuaid ◽  
Brian D. Sykes
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Rate Constants ◽  
Calcium Binding ◽  
Relative Displacement ◽  
Nuclear Magnetic Resonance Study ◽  
Stopped Flow ◽  
H Nmr ◽  
Nmr Methods ◽  
Nuclear Magnetic

The rate constants for the dissociation of the lanthanide Yb3+ from the CD and EF calcium-binding sites of carp parvalbumin (isoelectric point, 4.25) have been measured using optical stopped-flow and 1H nuclear magnetic resonance (NMR) methods. The off-rate constants for Yb3+ are 1.5 × 10−1 and 1.3 × 10−3 s−1 respectively, at pH 6.6 and 23 °C. The relative displacement of Ca2+ from the two sites by Yb3+ was determined from the observed amplitude of the fast and slow kinetic phases. Yb3+-shifted 1H-NMR spectra of parvalbumin are presented as a function of pH, concentration, and H2O:D2O ratio to relate the NMR results to the kinetic and optical results. The displacement of Cd2+ from parvalbumin by Yb3+ was studied using 113Cd NMR. All of the results show the sequential displacement of Ca2+ from the CD and EF sites of parvalbumin by Yb3+. Some results are also presented for Tb3+ and Gd3+.

Nuclear magnetic resonance studies. XXXI. Rearrangement and deuterium exchange through β-enolization in bicyclooctanones. An 2H nuclear magnetic resonance study.

1977 ◽  
Vol 55 (3) ◽  
pp. 447-453 ◽  
Author(s):  
A. K. Cheng ◽  
J. B. Stothers ◽  
C. T. Tan
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Nuclear Magnetic Resonance Study ◽  
Magnetic Resonance Study ◽  
Deuterium Incorporation ◽  
Proton Abstraction ◽  
Magnetic Resonance Studies ◽  
H Nmr ◽  
Derivatives Of ◽  
Nuclear Magnetic

The bicyclo[2.2.2]octan-2-one and -[3.2.1]octan-6-one skeletons are interconvertible under strongly basic conditions. Their α,α-dimethyl derivatives in tert-Buo−/tert-BuOH at 185 °C undergo very slow interconversion by β-proton abstraction. Using 2H nmr the stereoselectivity of deuterium incorporation at the β-methylene sites was established. The relative reactivities of β-methyl exchange in the [3.2.1] system were also determined. As models for this process, exchange in the α,α,α′,α′-tetramethyl derivatives of the monocyclic ketones, C5–C8, was also studied.

Multiple binding sites for local anesthetics in membranes: characterization of the sites and their equilibria by deuterium NMR of specifically deuterated procaine and tetracaine

1980 ◽  
Vol 58 (10) ◽  
pp. 986-995 ◽  
Author(s):  
Yvan Boulanger ◽  
Shirley Schreier ◽  
Leonard C. Leitch ◽  
Ian C. P. Smith
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Binding Sites ◽  
Local Anesthetics ◽  
Partition Coefficients ◽  
Low Ph ◽  
Weakly Bound ◽  
High Ph ◽  
Charged Form ◽  
Nuclear Magnetic

Anesthetics bound to model membranes were observed directly by means of deuterium nuclear magnetic resonance (NMR). The specifically deuterated local anesthetics procaine and tetracaine were synthesized, and their partition coefficients (water:phosphatidylcholine) and pKa values determined. The interaction of these anesthetics with lamellar dispersions of egg phosphatidylcholine was studied by 2H nuclear magnetic resonance and by electron spin resonance (ESR) of a spin-labelled phospholipid at low (5.5) and high (9.5) pH. The ESR experiments suggest that tetracaine intercalates in the membrane and that it equilibrates between water and the phospholipid bilayers of the multilamellar system. The NMR results are consistent with a model where the anesthetic is (I) free in water, (2) weakly bound, and (3) strongly bound to the membrane. A fast exchange exists between the two first sites, but exchange is slow with the third site. Binding of type 3 is observed only at high pH for procaine, whereas it is found both at low and high pH for tetracaine. Calculations of the partition coefficients for the charged and uncharged forms of tetracaine indicate that both sites, 2 and 3, are occupied by the charged form at low pH and by the uncharged form at high pH. The partition coefficient for the weakly bound species was estimated from an analysis of the dependence of line width on the lipid to water ratio. The NMR data suggest that the binding sites for the strongly bound charged and uncharged species are different, the former probably being closer to the membrane–water interface. Estimates of molecular order parameters for the strongly bound species indicate that it is located with its long molecular axis approximately parallel to the director for ordering of the fatty acyl chains. A small increase in lipid ordering by tetracaine is observed at low pH, as evidenced by 2H NMR of the deuterated N-methyl groups of phosphatidylcholine; the reverse occurs at high pH.

A structural reinvestigation of 4,6-dinitrobenzofuroxan by 1H, 13C, and 15N nuclear magnetic resonance

1989 ◽  
Vol 67 (3) ◽  
pp. 503-507 ◽  
Author(s):  
F. Terrier ◽  
J. C. Halle ◽  
P. MacCormack ◽  
M. J. Pouet
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Chemical Shifts ◽  
Nuclear Magnetic Resonance Study ◽  
H Nmr ◽  
Oxide Group ◽  
Proton Chemical Shifts ◽  
C Nmr ◽  
Nuclear Magnetic

A detailed nuclear magnetic resonance study of 4,6-dinitro-2,1,3-benzoxadiazole N-oxide (DNBF), which includes a 2D INADEQUATE analysis and experiments with samples 15N-labelled at the NO2 groups, is described. The results lead to an unambiguous assignment of the carbon and proton chemical shifts in various solvents. Some 1H and 13C data pertaining to 4,6-dinitro-2,1,3-benzoxadiazole (DNBZ), the deoxygenated analog of DNBF, are also reported, allowing the influence of the N-oxide group on the proton and carbon chemical shifts to be discussed. It is shown that all of the 1H nmr evidence so far reported for the characterization of DNBF σ adducts as arising from nucleophilic addition to the 7-position, i.e., as structure 2a, has no significance. That complexation actually occurs at this position is, however, convincingly demonstrated by 15N data. These also allow us to establish that this process is both kinetically and thermodynamically favored. Keywords: nitrobenzofuroxans, Meisenheimer complexes, 13C nmr of benzofuroxans, 2,1,3-benzoxadiazole N-oxides, nitrobenzofuroxan σ-adducts.

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