5, 10-Methylene-5, 6, 7, 8-tetrahydrofolate. Conformation of the Tetrahydropyrazine and Imidazoline Rings†

Martin Poe, L. M. Jackman, Stephen J. Benkovic

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

It is suggested from analysis of its 1H NMR spectrum and from model building that methylenetetrahydro-folate in solution at neutral and alkaline pH has a rigid conformation for its tetrahydropyrazine and imidazolidine rings. The proposed conformation in solution has three noteworthy features: (1) the tetrahydropyrazine ring is in a half-chair conformation with C6-H axial; (2) the imidazolidine ring is on the same side of the pyrimidine ring as C7 and is nearly planar, and the plane is at an angle of 120° to the pyrimidine ring plane; (3) the aromatic ring of the p-aminobenzoyl-l-glutamate moiety extends away from the pteridine rings, but this possibly may not be true for methylenetetrahydrofolate at neutral pH. The chemical shifts and spin-spin coupling constants of the 15 carbon-bound hydrogens of a diastereo-meric mixture of the two C6 stereoisomers and of the natural C6 stereoisomer of methylenetetrahydrofolate were measured at 25 °C and 300 MHz in 0.1 M NaOD and in 0.1 M sodium phosphate, pH 6.79. In 0.1 M NaOD and at pH∗ 6.79, these compounds had the same coupling constants between their C6, C7, C9, and C11 hydrogens. Also examined was a methylenetetrahydrofolate specifically deuterated at C7. The resonances corresponding to the two hydrogens on C7 had a geminal coupling to one another of 12 Hz and spin-spin couplings to C6-H of 10.0 and 3.0 Hz for the hydrogens trans and cis to C6-H, respectively. The two C9 resonances had geminal coupling of 9.5 Hz and spin-spin couplings to C6-H of 6.5 and 1.5 Hz for the hydrogens cis and trans to C6-H, respectively. The two resonances for the hydrogens on the carbon between N5 and N10, C11, had a chemical shift difference greater than 1 ppm and a geminal coupling of 5.0 Hz.

Original languageEnglish (US)
Pages (from-to)5527-5530
Number of pages4
JournalBiochemistry
Volume18
Issue number24
DOIs
StatePublished - Jan 1 1979

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Imidazolines
Conformations
Hydrogen
Imidazolidines
Stereoisomerism
Chemical shift
Carbon
Pteridines
Folic Acid
5,10-methylenetetrahydrofolic acid
Glutamic Acid
Nuclear magnetic resonance

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Poe, Martin ; Jackman, L. M. ; Benkovic, Stephen J. / 5, 10-Methylene-5, 6, 7, 8-tetrahydrofolate. Conformation of the Tetrahydropyrazine and Imidazoline Rings†. In: Biochemistry. 1979 ; Vol. 18, No. 24. pp. 5527-5530.
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abstract = "It is suggested from analysis of its 1H NMR spectrum and from model building that methylenetetrahydro-folate in solution at neutral and alkaline pH has a rigid conformation for its tetrahydropyrazine and imidazolidine rings. The proposed conformation in solution has three noteworthy features: (1) the tetrahydropyrazine ring is in a half-chair conformation with C6-H axial; (2) the imidazolidine ring is on the same side of the pyrimidine ring as C7 and is nearly planar, and the plane is at an angle of 120° to the pyrimidine ring plane; (3) the aromatic ring of the p-aminobenzoyl-l-glutamate moiety extends away from the pteridine rings, but this possibly may not be true for methylenetetrahydrofolate at neutral pH. The chemical shifts and spin-spin coupling constants of the 15 carbon-bound hydrogens of a diastereo-meric mixture of the two C6 stereoisomers and of the natural C6 stereoisomer of methylenetetrahydrofolate were measured at 25 °C and 300 MHz in 0.1 M NaOD and in 0.1 M sodium phosphate, pH 6.79. In 0.1 M NaOD and at pH∗ 6.79, these compounds had the same coupling constants between their C6, C7, C9, and C11 hydrogens. Also examined was a methylenetetrahydrofolate specifically deuterated at C7. The resonances corresponding to the two hydrogens on C7 had a geminal coupling to one another of 12 Hz and spin-spin couplings to C6-H of 10.0 and 3.0 Hz for the hydrogens trans and cis to C6-H, respectively. The two C9 resonances had geminal coupling of 9.5 Hz and spin-spin couplings to C6-H of 6.5 and 1.5 Hz for the hydrogens cis and trans to C6-H, respectively. The two resonances for the hydrogens on the carbon between N5 and N10, C11, had a chemical shift difference greater than 1 ppm and a geminal coupling of 5.0 Hz.",
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5, 10-Methylene-5, 6, 7, 8-tetrahydrofolate. Conformation of the Tetrahydropyrazine and Imidazoline Rings†. / Poe, Martin; Jackman, L. M.; Benkovic, Stephen J.

In: Biochemistry, Vol. 18, No. 24, 01.01.1979, p. 5527-5530.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 5, 10-Methylene-5, 6, 7, 8-tetrahydrofolate. Conformation of the Tetrahydropyrazine and Imidazoline Rings†

AU - Poe, Martin

AU - Jackman, L. M.

AU - Benkovic, Stephen J.

PY - 1979/1/1

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N2 - It is suggested from analysis of its 1H NMR spectrum and from model building that methylenetetrahydro-folate in solution at neutral and alkaline pH has a rigid conformation for its tetrahydropyrazine and imidazolidine rings. The proposed conformation in solution has three noteworthy features: (1) the tetrahydropyrazine ring is in a half-chair conformation with C6-H axial; (2) the imidazolidine ring is on the same side of the pyrimidine ring as C7 and is nearly planar, and the plane is at an angle of 120° to the pyrimidine ring plane; (3) the aromatic ring of the p-aminobenzoyl-l-glutamate moiety extends away from the pteridine rings, but this possibly may not be true for methylenetetrahydrofolate at neutral pH. The chemical shifts and spin-spin coupling constants of the 15 carbon-bound hydrogens of a diastereo-meric mixture of the two C6 stereoisomers and of the natural C6 stereoisomer of methylenetetrahydrofolate were measured at 25 °C and 300 MHz in 0.1 M NaOD and in 0.1 M sodium phosphate, pH 6.79. In 0.1 M NaOD and at pH∗ 6.79, these compounds had the same coupling constants between their C6, C7, C9, and C11 hydrogens. Also examined was a methylenetetrahydrofolate specifically deuterated at C7. The resonances corresponding to the two hydrogens on C7 had a geminal coupling to one another of 12 Hz and spin-spin couplings to C6-H of 10.0 and 3.0 Hz for the hydrogens trans and cis to C6-H, respectively. The two C9 resonances had geminal coupling of 9.5 Hz and spin-spin couplings to C6-H of 6.5 and 1.5 Hz for the hydrogens cis and trans to C6-H, respectively. The two resonances for the hydrogens on the carbon between N5 and N10, C11, had a chemical shift difference greater than 1 ppm and a geminal coupling of 5.0 Hz.

AB - It is suggested from analysis of its 1H NMR spectrum and from model building that methylenetetrahydro-folate in solution at neutral and alkaline pH has a rigid conformation for its tetrahydropyrazine and imidazolidine rings. The proposed conformation in solution has three noteworthy features: (1) the tetrahydropyrazine ring is in a half-chair conformation with C6-H axial; (2) the imidazolidine ring is on the same side of the pyrimidine ring as C7 and is nearly planar, and the plane is at an angle of 120° to the pyrimidine ring plane; (3) the aromatic ring of the p-aminobenzoyl-l-glutamate moiety extends away from the pteridine rings, but this possibly may not be true for methylenetetrahydrofolate at neutral pH. The chemical shifts and spin-spin coupling constants of the 15 carbon-bound hydrogens of a diastereo-meric mixture of the two C6 stereoisomers and of the natural C6 stereoisomer of methylenetetrahydrofolate were measured at 25 °C and 300 MHz in 0.1 M NaOD and in 0.1 M sodium phosphate, pH 6.79. In 0.1 M NaOD and at pH∗ 6.79, these compounds had the same coupling constants between their C6, C7, C9, and C11 hydrogens. Also examined was a methylenetetrahydrofolate specifically deuterated at C7. The resonances corresponding to the two hydrogens on C7 had a geminal coupling to one another of 12 Hz and spin-spin couplings to C6-H of 10.0 and 3.0 Hz for the hydrogens trans and cis to C6-H, respectively. The two C9 resonances had geminal coupling of 9.5 Hz and spin-spin couplings to C6-H of 6.5 and 1.5 Hz for the hydrogens cis and trans to C6-H, respectively. The two resonances for the hydrogens on the carbon between N5 and N10, C11, had a chemical shift difference greater than 1 ppm and a geminal coupling of 5.0 Hz.

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