Abstract
We present a novel series of hydrogen-bonded, polycrystalline 1:1 complexes of Schiff base models of the cofactor pyridoxal-5′-phosphate (PLP) with carboxylic acids that mimic the cofactor in a variety of enzyme active sites. These systems contain an intramolecular OHN hydrogen bond characterized by a fast proton tautomerism as well as a strong intermolecular OHN hydrogen bond between the pyridine ring of the cofactor and the carboxylic acid. In particular, the aldenamine and aldimine Schiff bases N-(pyridoxylidene) tolylamine and N-(pyridoxylidene)methylamine, as well as their adducts, were synthesized and studied using 15N CP and 1H NMR techniques under static and/or MAS conditions. The geometries of the hydrogen bonds were obtained from X-ray structures, 1H and 15N chemical shift correlations, secondary H/D isotope effects on the 15N chemical shifts, or directly by measuring the dipolar 2H-15N couplings of static samples of the deuterated compounds. An interesting coupling of the two "functional" OHN hydrogen bonds was observed. When the Schiff base nitrogen atoms of the adducts carry an aliphatic substituent such as in the internal and external aldimines of PLP in the enzymatic environment, protonation of the ring nitrogen shifts the proton in the intramolecular OHN hydrogen bond from the oxygen to the Schiff base nitrogen. This effect, which increases the positive charge on the nitrogen atom, has been discussed as a prerequisite for cofactor activity. This coupled proton transfer does not occur if the Schiff base nitrogen atom carries an aromatic substituent.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4440-4455 |
| Number of pages | 16 |
| Journal | Journal of the American Chemical Society |
| Volume | 129 |
| Issue number | 14 |
| DOIs | |
| State | Published - Apr 11 2007 |
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- Chemistry(all)
Cite this
Coupling of functional hydrogen bonds in pyridoxal-5′-phosphate- enzyme model systems observed by solid-state NMR spectroscopy. / Sharif, Shasad; Schagen, David; Toney, Michael D.; Limbach, Hans Heinrich.
In: Journal of the American Chemical Society, Vol. 129, No. 14, 11.04.2007, p. 4440-4455.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Coupling of functional hydrogen bonds in pyridoxal-5′-phosphate- enzyme model systems observed by solid-state NMR spectroscopy
AU - Sharif, Shasad
AU - Schagen, David
AU - Toney, Michael D.
AU - Limbach, Hans Heinrich
PY - 2007/4/11
Y1 - 2007/4/11
N2 - We present a novel series of hydrogen-bonded, polycrystalline 1:1 complexes of Schiff base models of the cofactor pyridoxal-5′-phosphate (PLP) with carboxylic acids that mimic the cofactor in a variety of enzyme active sites. These systems contain an intramolecular OHN hydrogen bond characterized by a fast proton tautomerism as well as a strong intermolecular OHN hydrogen bond between the pyridine ring of the cofactor and the carboxylic acid. In particular, the aldenamine and aldimine Schiff bases N-(pyridoxylidene) tolylamine and N-(pyridoxylidene)methylamine, as well as their adducts, were synthesized and studied using 15N CP and 1H NMR techniques under static and/or MAS conditions. The geometries of the hydrogen bonds were obtained from X-ray structures, 1H and 15N chemical shift correlations, secondary H/D isotope effects on the 15N chemical shifts, or directly by measuring the dipolar 2H-15N couplings of static samples of the deuterated compounds. An interesting coupling of the two "functional" OHN hydrogen bonds was observed. When the Schiff base nitrogen atoms of the adducts carry an aliphatic substituent such as in the internal and external aldimines of PLP in the enzymatic environment, protonation of the ring nitrogen shifts the proton in the intramolecular OHN hydrogen bond from the oxygen to the Schiff base nitrogen. This effect, which increases the positive charge on the nitrogen atom, has been discussed as a prerequisite for cofactor activity. This coupled proton transfer does not occur if the Schiff base nitrogen atom carries an aromatic substituent.
AB - We present a novel series of hydrogen-bonded, polycrystalline 1:1 complexes of Schiff base models of the cofactor pyridoxal-5′-phosphate (PLP) with carboxylic acids that mimic the cofactor in a variety of enzyme active sites. These systems contain an intramolecular OHN hydrogen bond characterized by a fast proton tautomerism as well as a strong intermolecular OHN hydrogen bond between the pyridine ring of the cofactor and the carboxylic acid. In particular, the aldenamine and aldimine Schiff bases N-(pyridoxylidene) tolylamine and N-(pyridoxylidene)methylamine, as well as their adducts, were synthesized and studied using 15N CP and 1H NMR techniques under static and/or MAS conditions. The geometries of the hydrogen bonds were obtained from X-ray structures, 1H and 15N chemical shift correlations, secondary H/D isotope effects on the 15N chemical shifts, or directly by measuring the dipolar 2H-15N couplings of static samples of the deuterated compounds. An interesting coupling of the two "functional" OHN hydrogen bonds was observed. When the Schiff base nitrogen atoms of the adducts carry an aliphatic substituent such as in the internal and external aldimines of PLP in the enzymatic environment, protonation of the ring nitrogen shifts the proton in the intramolecular OHN hydrogen bond from the oxygen to the Schiff base nitrogen. This effect, which increases the positive charge on the nitrogen atom, has been discussed as a prerequisite for cofactor activity. This coupled proton transfer does not occur if the Schiff base nitrogen atom carries an aromatic substituent.
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U2 - 10.1021/ja066240h
DO - 10.1021/ja066240h
M3 - Article
C2 - 17371021
AN - SCOPUS:34247114263
VL - 129
SP - 4440
EP - 4455
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 14
ER -