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 (1) 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.

The limitations of present methods of synthesizing 1,2-diallcylhytlrazi~~es are discussed. A new method of obtaining these colllpounds in good yields by the reduction of azines with lithium aluminum hydride is reported. Lithium a l u m i n~~m deuteride was employed as a tracer to investigate the mechanism oi the reaction. The 1,2-dialkylhydrazines were oxidized to the azoparaffins in over 90% yields by mercuric oxide in water. INTRODUCTIONAn important source of free radicals for kinetic investigations is the thennal or photochemical decomposition of azoalkanes (11). Up to now the availability of these compounds has been limited on account of the difficulty of obtaining the 1,2-dialkylhydrazines. For example, of the lower azoalltanes only the methyl and isopropyl compounds have long been known, azoethane having been prepared quite recently (15). This work was undertaken t o develop a general method of preparing 1,2-dialkylhydrazines and thereby to provide a route to the required azocompounds.Knorr and Icohler (9) obtained 1,2-dimethylhydrazine by alltaline hydrolysis of dimethylpyrazole and characterized it by means of several derivatives. I t had previously been prepared by Harries and I

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Lithium, sodium, potassium, cesium, and ammonium palmityl sulfates were prepared by sulfonation of n-hexadecanol, followed by treatment with the corresponding alkali carbonates; selectively deuterated palmityl sulfates were also synthesized to aid the assignment of certain vibrational modes. The infrared and Raman spectra of the polycrystalline solids were interpreted and discussed in terms of acyl chain and head group vibrations. Spectral evidence is presented for the existence of different solid polymorphic forms.