Determination of dissociation constants of (4RS)-[4-carboxy-5,8,11-tris(carboxymethyl)-1-phenyl-2-oxa-5,8,11-triazatridecan-13-oic acid] in water and biological fluids by means of nuclear magnetic resonance spectroscopy and the DISCO software package

Anal Biochem. 2003 Aug 15;319(2):195-205. doi: 10.1016/s0003-2697(03)00301-4.

Abstract

The pK(A) values of (4RS)-[4-carboxy-5,8,11-tris(carboxymethyl)-1-phenyl-2-oxa-5,8,11-triazatridecan-13-oic acid] (BOPTA), a polyprotic molecule whose gadolinium complex is an important magnetic resonance imaging contrast agent for clinical use, have been determined in water, in physiologic solution (PS), in serum (S), and in cerebrospinal fluid (CSF), by means of 13C nuclear magnetic resonance spectroscopy data processed by a dedicated software package called DISCO. The aim of this study was to supply the BOPTA pK(A) values in media very similar to the in vivo environment and, consequently, to get a picture of the in vivo behavior of its Gd complex, whose thermodynamic stability is directly linked to the pK(A) values. The pK(A) values appeared to be almost equal both in D(2)O and in PS, while pK(1) and pK(5) values in CSF differ a little. In S, only pK(2) and pK(3) were calculated due to the narrow pH range used for data collection. However, these pK(A) values were found equal to those in the other media. These results represent the first direct spectroscopic evidence of a substantial invariability of BOPTA behavior in different media and they justify the extrapolation to biological fluids of the data obtained in water. The values also confirmed the high-quality performance of DISCO in calculating pK(A) values of polyprotic molecules in complex media.

MeSH terms

  • Carbon Isotopes
  • Deuterium Oxide
  • Gadolinium / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Isotonic Solutions / chemistry
  • Kinetics
  • Magnetic Resonance Spectroscopy / methods
  • Meglumine / analogs & derivatives*
  • Meglumine / blood
  • Meglumine / cerebrospinal fluid
  • Meglumine / chemistry*
  • Organometallic Compounds / blood
  • Organometallic Compounds / cerebrospinal fluid
  • Organometallic Compounds / chemistry*
  • Serum / chemistry
  • Sodium Chloride / chemistry
  • Software
  • Thermodynamics
  • Water / chemistry*

Substances

  • Carbon Isotopes
  • Isotonic Solutions
  • Organometallic Compounds
  • Water
  • gadobenic acid
  • Sodium Chloride
  • Meglumine
  • Gadolinium
  • Deuterium Oxide