Aromatic hydroxylation by cytochrome P450 : model calculations of mechanism and substituent effects
The mechanism and selectivity of aromatic hydroxylation by cytochrome P450 enzymes is explored using new B3LYP density functional theory computations. The calculations, using a realistic porphyrin model system, show that rate-determining addition of compound I to an aromatic carbon atom proceeds via a transition state with partial radical and cationic character. Reactivity is shown to depend strongly on ring substituents, with both electron-withdrawing and -donating groups strongly decreasing the addition barrier in the para position, and it is shown that the calculated barrier heights can be reproduced by a new dual-parameter equation based on radical and cationic Hammett sigma parameters.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2003 |
|---|---|
| Erschienen: |
2003 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:125 |
|---|---|
| Enthalten in: |
Journal of the American Chemical Society - 125(2003), 49 vom: 10. Dez., Seite 15004-5 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Bathelt, Christine M [VerfasserIn] |
|---|
| Themen: |
9035-51-2 |
|---|
| Anmerkungen: |
Date Completed 26.02.2004 Date Revised 15.11.2006 published: Print Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM143688561 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM143688561 | ||
| 003 | DE-627 | ||
| 005 | 20231223031441.0 | ||
| 007 | tu | ||
| 008 | 231223s2003 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0479.xml |
| 035 | |a (DE-627)NLM143688561 | ||
| 035 | |a (NLM)14653732 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Bathelt, Christine M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Aromatic hydroxylation by cytochrome P450 |b model calculations of mechanism and substituent effects |
| 264 | 1 | |c 2003 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 26.02.2004 | ||
| 500 | |a Date Revised 15.11.2006 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The mechanism and selectivity of aromatic hydroxylation by cytochrome P450 enzymes is explored using new B3LYP density functional theory computations. The calculations, using a realistic porphyrin model system, show that rate-determining addition of compound I to an aromatic carbon atom proceeds via a transition state with partial radical and cationic character. Reactivity is shown to depend strongly on ring substituents, with both electron-withdrawing and -donating groups strongly decreasing the addition barrier in the para position, and it is shown that the calculated barrier heights can be reproduced by a new dual-parameter equation based on radical and cationic Hammett sigma parameters | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Hydrocarbons, Aromatic |2 NLM | |
| 650 | 7 | |a Cytochrome P-450 Enzyme System |2 NLM | |
| 650 | 7 | |a 9035-51-2 |2 NLM | |
| 700 | 1 | |a Ridder, Lars |e verfasserin |4 aut | |
| 700 | 1 | |a Mulholland, Adrian J |e verfasserin |4 aut | |
| 700 | 1 | |a Harvey, Jeremy N |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of the American Chemical Society |d 1945 |g 125(2003), 49 vom: 10. Dez., Seite 15004-5 |w (DE-627)NLM00000569X |x 1520-5126 |7 nnns |
| 773 | 1 | 8 | |g volume:125 |g year:2003 |g number:49 |g day:10 |g month:12 |g pages:15004-5 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 125 |j 2003 |e 49 |b 10 |c 12 |h 15004-5 | ||