Premium
THE IONIZATION OF MORPHINE, HYDROXY AMPHETAMINE AND (+)‐TUBOCURARINE CHLORIDE AND A NEW METHOD FOR CALCULATING ZWITTERION CONSTANTS
Author(s) -
BARLOW R.B.
Publication year - 1982
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1982.tb09167.x
Subject(s) - zwitterion , chemistry , absorbance , chloride , degree (music) , chromatography , molecule , organic chemistry , physics , acoustics
1 An improved method for estimating the zwitterion constants of phenolic amines is described which involves the exploratory least‐squares fit of absorbance (at a suitable wavelength) to pH, starting with estimates of pK 1 and pK 2 obtained electrometrically. 2 With the method it is possible to see that hydroxyamphetamine (α‐methyltyramine) has a higher zwitterion constant than tyramine and the zwitterion constants of both compounds are lower at 37°C than at 25°C. 3 The zwitterion constant of morphine is not reduced by raising the temperature from 25° to 37°C and the effect of temperature is much greater in compounds with a primary or secondary amino group than with those containing a tertiary amino group. Some zwitterions may be stabilized by hydration and their formation will be reduced by a rise in temperature which will break up water structure. 4 From electrometric titrations with (+)‐tubocurarine chloride in 0.1 m NaCl estimates of pK 1 , pK 2 and pK 3 were 7.6, 8.65 and 9.65 at 25°C and 7.4, 8.6 and 9.7 at 37°C, compared with 7.8, 8.85 and 9.75 given by Perrin (1980). However, the effects of pH on absorbance show that the phenolic groups lose a proton before the ammonium group so there is extensive zwitterion formation which is probably greater at 25° than at 37°C. The p ‐phenolic group (position 13) probably ionizes first with the phenate form stabilized by hydration involving water molecules and the protonated form of the (1‐) ammonium group.