Molecular Conformations of 4-Aminomethyl-1-cyclohexanecarboxylic Acids in Aqueous Solution

The structures of cis- and trans-4-aminomethyl-1 -cyclohexanecarboxylic acids were studied by proton and carbon-13 NMR, and by semiempirical molecular orbital methods (CNDO/2 and MNDO). Both isomers exist in zwitter ionic forms in aqueous solution. It was found that the most stable conformations for them are all staggered forms: the diequatorial conformer in the trans form and the axial carboxyl group in the cis form. These preferred conformers are similar to those in crystalline states. In these conformers the deformation is very small in the cyclohexane ring of the trans form. The atomic distance between the nitrogen of amino group and the carbon of carboxyl group in the preferred conformer of trans form is 0.65 nm and that in cis form is 0.55 nm. This distance of 0.65 nm will play an important role in the antifibrinolytic effect.

[1]  B. Granstrand,et al.  Biochemistry and toxicology of amikapron; the antifibrinolytically active isomer of AMCHA. (A comparative study with epsilon-aminocaproic acid). , 2009, Acta pharmacologica et toxicologica.

[2]  Kaori Tanaka,et al.  Molecular Conformations of γ-Aminobutyric Acid and γ-Amino-β-hydroxybutyric Acid in Aqueous Solution , 1978 .

[3]  Walter Thiel,et al.  Ground States of Molecules. 38. The MNDO Method. Approximations and Parameters , 1977 .

[4]  Walter Thiel,et al.  Ground States of Molecules. 39. MNDO Results for Molecules Containing Hydrogen, Carbon, Nitrogen, and Oxygen , 1977 .

[5]  F. Inagaki,et al.  Conformation of Thymidine 3′,5′-Cyclic Phosphate in Aqueous Solution. Compatibility of the Information from the Lanthanide-Ion Probe and the Spin-Coupling Constants , 1976 .

[6]  F. Inagaki,et al.  Lanthanide-Induced Nuclear Magnetic Resonance Shifts and Molecular Structure of L-Azetidine-2-Carboxylic Acid. II. Determination of Molecular Conformation , 1975 .

[7]  F. Inagaki,et al.  Lanthanide-Induced Nuclear Magnetic Resonance Shifts and Molecular Structure of L-Azetidine-2-Carboxylic Acid. I. Evaluation of the Shifts Intrinsic to the Lanthanide-Substrate 1:1 Complex , 1975 .

[8]  C. D. Barry,et al.  Quantitative determination of conformations of flexible molecules in solution using lanthanide ions as nuclear magnetic resonance probes: application to adenosine-5'-monophosphate. , 1974, Journal of molecular biology.

[9]  D. Grant,et al.  Carbon-13 magnetic resonance. XXIV. Perhydroanthracenes and perhydrophenanthrenes , 1974 .

[10]  R. Lemieux,et al.  Nuclear magnetic resonance in carbohydrate chemistry , 1973 .

[11]  D. Grant,et al.  Carbon-13 magnetic resonance. XXIII. Methyldecalins , 1973 .

[12]  D. Grant,et al.  Carbon-13 magnetic resonance. XXI. Steric interactions in the methylcyclohexanes , 1972 .

[13]  Y. Abiko,et al.  Plasminogen-plasmin system. VII. Potentiation of antifibrinolytic action of a synthetic inhibitor, tranexamic acid, by alpha 2-macroglobulin antiplasmin. , 1970, Biochimica et biophysica acta.

[14]  J. Pople,et al.  Approximate self-consistent molecular orbital theory of nuclear spin coupling. IV. Vicinal proton-proton coupling constants in substituted ethanes and ethylenes and related compounds , 1970 .

[15]  J. Pople,et al.  Self‐Consistent Perturbation Theory. II. Nuclear‐Spin Coupling Constants , 1968 .

[16]  N. S. Ostlund,et al.  Self‐Consistent Perturbation Theory. I. Finite Perturbation Methods , 1968 .

[17]  S. Kadoya,et al.  Medicinal chemical studies on antiplasmin drugs. II. Separation of stereoisomers of 4-aminomethylcyclohexanecarboxylic acid and assignment of their configuration. , 1968, Chemical and pharmaceutical bulletin.

[18]  D. Grant,et al.  Carbon-13 magnetic resonance. IX. Methylcyclohexanes , 1967 .

[19]  Y. Iitaka,et al.  The crystal structures of trans and cis-4-aminomethylcyclohexane-1-carboxylic acid hydrohalides , 1966 .

[20]  S. Castellano,et al.  ANALYSIS OF NMR SPECTRA BY LEAST SQUARES , 1964 .

[21]  R. C. Ferguson,et al.  Computer Analysis of NMR Spectra: Magnetic Equivalence Factoring , 1964 .

[22]  K. Pachler.  Nuclear magnetic resonance study of some α-amino acids—II. Rotational isomerism , 1964 .

[23]  R. E. Robertson,et al.  ISOTROPIC NUCLEAR RESONANCE SHIFTS , 1958 .

[24]  A. Bothner‐By,et al.  ORGANIC ANALYTICAL APPLICATION OF NUCLEAR MAGNETIC RESONANCE , 1958 .

[25]  I. Morishima,et al.  Conformational dependence of the inductive effect in the .sigma.-electron system as studied by carbon-13 nuclear magnetic resonance , 1973 .

[26]  P. Groth.  Crystal structure of the trans form of 1,4-aminomethylcyclohexanecarboxylic acid. , 1968, Acta Chemica Scandinavica.

[27]  T. Enari,et al.  Cis-trans Relationship between the Two Amino-acids Obtained by Hydrogenation of p-Aminomethyl Benzoic Acid. , 1965 .

[28]  S. Okamoto,et al.  INFLUENCE OF AMCHA ON THE ACTIVITY OF FIBRINOLYSIN (PLASMIN) , 1962 .

[29]  S. Okamoto,et al.  AMINO-METHYL-CYCLOHEXANE-CARBOXYLIC ACID: AMCHA , 1962 .

[30]  M. Karplus.  Contact Electron‐Spin Coupling of Nuclear Magnetic Moments , 1959 .