The oxidation of alkenes by high-valent iron-oxo active species {normally|usually|typically|generally|commonly|ordinarily} {leads to|results in} the formation {of the|from the|in the|on the|with the|of your} corresponding epoxides. {Rarely|Seldom|Hardly ever}, carbonyl compounds are observed as a side {product|item|solution} {of the|from the|in the|on the|with the|of your} reaction. {However|Nevertheless|Nonetheless|Even so|On the other hand|Having said that}, the selective formation of carbonyl compounds from alkenes {using|utilizing|making use of|employing|working with|applying} iron-oxo species and {small|little|tiny|modest|smaller|compact} molecule catalysts has not {yet|however|but} been {achieved|accomplished}. {Recently|Lately|Not too long ago}, {a new|a brand new} P450-based enzyme (aMOx) has been engineered {through|via|by means of|by way of} laboratory directed evolution to {directly|straight} oxidize styrenes to their corresponding aldehydes. This transformation {uses|utilizes|makes use of} an enzymatic iron-oxo species as catalytic oxidant and generates aldehydes with {high|higher} activity and selectivity {while|whilst|although|even though|when|though} suppressing epoxidation.{Here|Right here}, we combine {extensive|in depth|substantial|comprehensive} computational modelling {together|with each other|collectively} with experimental mechanistic investigations to study the reaction mechanism and unravel the molecular basis behind the selectivity {achieved|accomplished} by the laboratory evolved aMOx enzyme. We {found|discovered|identified|located} that alkene epoxidation and carbonyl formation pathways diverge from a {common|typical|frequent|widespread|prevalent|popular} covalent radical intermediate generated {after|following|right after|soon after|immediately after|just after} {the first|the very first|the initial} C–O bond formation. {Although|Even though|Though|Despite the fact that|While} {both|each} pathways are accessible and {very|extremely|really|quite|incredibly|pretty} {similar|comparable|equivalent|related} in {energy|power}, intrinsic dynamic effects {determine|figure out|decide|establish|ascertain|identify} the {strong|powerful|robust|sturdy} preference for epoxidation. We {discovered|found} that aMOx overrides these intrinsic dynamic preferences by controlling the accessible conformations {of the|from the|in the|on the|with the|of your} covalent radical intermediate. This disfavors epoxidation and facilitates the formation of a {key|important|crucial|essential} carbocation intermediate that generates the aldehyde {product|item|solution} {through|via|by means of|by way of} a {fast|quick|quickly|rapidly|rapid|speedy} 1,2-hydride migration. Computations predicted that the hydride migration is stereoselective {due to|because of|as a result of|on account of|resulting from|as a consequence of} the conformational {control|manage|handle} {over|more than} the intermediate species when formed {in the|within the|inside the} enzyme active {site|website|web site|internet site|web-site|web page}. These predictions {were|had been|have been} corroborated by experiments {using|utilizing|making use of|employing|working with|applying} deuterated styrene substrates, which proved that the hydride migration is cis- and enantioselective.Our {results|outcomes|final results|benefits} demonstrate that directed evolution tailored a {highly|extremely|very|hugely} {specific|particular|certain|distinct|precise} active {site|website|web site|internet site|web-site|web page} that imposes {strong|powerful|robust|sturdy} steric {control|manage|handle} {over|more than} {key|important|crucial|essential} fleeting biocatalytic intermediates, {which is|that is|which can be} {essential|important|crucial|vital|necessary|critical} for accessing the carbonyl forming pathway and {preventing|stopping} competing epoxidation. Oxetane-2-carboxylic acid web 1247542-90-0 supplier PMID:23614016
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