Transition state structure of the solvolytic hydrolysis of NAD+

Paul J. Berti, Vern L. Schramm

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The transition state structure has been determined for the pH- independent solvolytic hydrolysis of NAD+. The structure is based on kinetic isotope effects (KIEs) measured for NAD+'s labeled in various positions of the ribose ring and in the leaving group nitrogen. The KIEs for reactions performed at 100°C in 50 mM NaOAc (pH 4.0) were as follows: 1-15N, 1.020 ± 0.007; 1'-14C, 1.016 ± 0.002; [1-15N,1'-14C], 1.034 ± 0.002; 1'- 3H, 1.194 ± 0.005; 2'-3H, 1.114 ± 0.004; 4'-3H, 0.0997 ± 0.001; 5'3H, 1.000 ± 0.003; 4'-18O, 0.988 ± 0.007. The transition state structure was determined using bond energy/bond order vibrational analysis to predict KIEs for trial transition state models. The structure that most closely matches the experimental KIEs defines the transition state. A structure interpolation method was developed to generate trial transition state structures and thereby systematically search reaction coordinate space. Structures are generated by interpolation between reference structures, reactant NAD+ and a hypothetical {ribo-oxocarbenium ion plus nicotinamide} structure. The point in reaction coordinate space where all the predicted KIEs matched the measured ones was considered to locate the transition state structure. This occurred when the residual bond order to the leaving group nicotinamide, n(LG,TS), was 0.02 (bond length = 2.65 Å) and the bond order to the approaching nucleophile, n(Nu,TS), was 0.005 (3.00 Å). Thus, bond-breaking and bond-making in this A(N)D(N) reaction are asynchronous, and the transition state has a highly oxocarbenium ion-like character.

Original languageEnglish (US)
Pages (from-to)12069-12078
Number of pages10
JournalJournal of the American Chemical Society
Volume119
Issue number50
DOIs
StatePublished - Dec 17 1997

Fingerprint

Isotopes
NAD
Hydrolysis
Kinetics
Niacinamide
Interpolation
Ions
Nucleophiles
Ribose
Chemical bonds
Bond length
Nitrogen

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Transition state structure of the solvolytic hydrolysis of NAD+. / Berti, Paul J.; Schramm, Vern L.

In: Journal of the American Chemical Society, Vol. 119, No. 50, 17.12.1997, p. 12069-12078.

Research output: Contribution to journalArticle

@article{cb6d36a300eb4c648f7ac4a34cf6a158,
title = "Transition state structure of the solvolytic hydrolysis of NAD+",
abstract = "The transition state structure has been determined for the pH- independent solvolytic hydrolysis of NAD+. The structure is based on kinetic isotope effects (KIEs) measured for NAD+'s labeled in various positions of the ribose ring and in the leaving group nitrogen. The KIEs for reactions performed at 100°C in 50 mM NaOAc (pH 4.0) were as follows: 1-15N, 1.020 ± 0.007; 1'-14C, 1.016 ± 0.002; [1-15N,1'-14C], 1.034 ± 0.002; 1'- 3H, 1.194 ± 0.005; 2'-3H, 1.114 ± 0.004; 4'-3H, 0.0997 ± 0.001; 5'3H, 1.000 ± 0.003; 4'-18O, 0.988 ± 0.007. The transition state structure was determined using bond energy/bond order vibrational analysis to predict KIEs for trial transition state models. The structure that most closely matches the experimental KIEs defines the transition state. A structure interpolation method was developed to generate trial transition state structures and thereby systematically search reaction coordinate space. Structures are generated by interpolation between reference structures, reactant NAD+ and a hypothetical {ribo-oxocarbenium ion plus nicotinamide} structure. The point in reaction coordinate space where all the predicted KIEs matched the measured ones was considered to locate the transition state structure. This occurred when the residual bond order to the leaving group nicotinamide, n(LG,TS), was 0.02 (bond length = 2.65 {\AA}) and the bond order to the approaching nucleophile, n(Nu,TS), was 0.005 (3.00 {\AA}). Thus, bond-breaking and bond-making in this A(N)D(N) reaction are asynchronous, and the transition state has a highly oxocarbenium ion-like character.",
author = "Berti, {Paul J.} and Schramm, {Vern L.}",
year = "1997",
month = "12",
day = "17",
doi = "10.1021/ja971316i",
language = "English (US)",
volume = "119",
pages = "12069--12078",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "50",

}

TY - JOUR

T1 - Transition state structure of the solvolytic hydrolysis of NAD+

AU - Berti, Paul J.

AU - Schramm, Vern L.

PY - 1997/12/17

Y1 - 1997/12/17

N2 - The transition state structure has been determined for the pH- independent solvolytic hydrolysis of NAD+. The structure is based on kinetic isotope effects (KIEs) measured for NAD+'s labeled in various positions of the ribose ring and in the leaving group nitrogen. The KIEs for reactions performed at 100°C in 50 mM NaOAc (pH 4.0) were as follows: 1-15N, 1.020 ± 0.007; 1'-14C, 1.016 ± 0.002; [1-15N,1'-14C], 1.034 ± 0.002; 1'- 3H, 1.194 ± 0.005; 2'-3H, 1.114 ± 0.004; 4'-3H, 0.0997 ± 0.001; 5'3H, 1.000 ± 0.003; 4'-18O, 0.988 ± 0.007. The transition state structure was determined using bond energy/bond order vibrational analysis to predict KIEs for trial transition state models. The structure that most closely matches the experimental KIEs defines the transition state. A structure interpolation method was developed to generate trial transition state structures and thereby systematically search reaction coordinate space. Structures are generated by interpolation between reference structures, reactant NAD+ and a hypothetical {ribo-oxocarbenium ion plus nicotinamide} structure. The point in reaction coordinate space where all the predicted KIEs matched the measured ones was considered to locate the transition state structure. This occurred when the residual bond order to the leaving group nicotinamide, n(LG,TS), was 0.02 (bond length = 2.65 Å) and the bond order to the approaching nucleophile, n(Nu,TS), was 0.005 (3.00 Å). Thus, bond-breaking and bond-making in this A(N)D(N) reaction are asynchronous, and the transition state has a highly oxocarbenium ion-like character.

AB - The transition state structure has been determined for the pH- independent solvolytic hydrolysis of NAD+. The structure is based on kinetic isotope effects (KIEs) measured for NAD+'s labeled in various positions of the ribose ring and in the leaving group nitrogen. The KIEs for reactions performed at 100°C in 50 mM NaOAc (pH 4.0) were as follows: 1-15N, 1.020 ± 0.007; 1'-14C, 1.016 ± 0.002; [1-15N,1'-14C], 1.034 ± 0.002; 1'- 3H, 1.194 ± 0.005; 2'-3H, 1.114 ± 0.004; 4'-3H, 0.0997 ± 0.001; 5'3H, 1.000 ± 0.003; 4'-18O, 0.988 ± 0.007. The transition state structure was determined using bond energy/bond order vibrational analysis to predict KIEs for trial transition state models. The structure that most closely matches the experimental KIEs defines the transition state. A structure interpolation method was developed to generate trial transition state structures and thereby systematically search reaction coordinate space. Structures are generated by interpolation between reference structures, reactant NAD+ and a hypothetical {ribo-oxocarbenium ion plus nicotinamide} structure. The point in reaction coordinate space where all the predicted KIEs matched the measured ones was considered to locate the transition state structure. This occurred when the residual bond order to the leaving group nicotinamide, n(LG,TS), was 0.02 (bond length = 2.65 Å) and the bond order to the approaching nucleophile, n(Nu,TS), was 0.005 (3.00 Å). Thus, bond-breaking and bond-making in this A(N)D(N) reaction are asynchronous, and the transition state has a highly oxocarbenium ion-like character.

UR - http://www.scopus.com/inward/record.url?scp=0031576672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031576672&partnerID=8YFLogxK

U2 - 10.1021/ja971316i

DO - 10.1021/ja971316i

M3 - Article

AN - SCOPUS:0031576672

VL - 119

SP - 12069

EP - 12078

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 50

ER -