CCL: Case Studies of QM Computational Chemistry in Reactivity

 Sent to CCL by: "Bashford, Don" [Don.Bashford^_^]
 Hi Peter,
 I have a case in which QM calculations by me (Bashford) predicted a meta-stable
 carbocation intermediate following the elimination of pyrophosphate from
 dihydropterin-PP in the mechanism of Dihydropteroate synthase (DHPS), and this
 intermediate was seen in a subsequent X-ray structure. The in-crystal experiment
 also supported the SN1-like mechanism that the calculation suggested (Yun et
 al., 2012, Science 335: 1110-1114).
 This enzyme is an important anti-bacterial target, as it is now known to be the
 target of the sulfa-drugs. It is part of the bacterial folate-synthesis pathway,
 which higher animals do not have. Sulfa-drug resistance has come about through
 mutations of DHPS.
 Don Bashford
 -----Original Message-----
 > From:^ [^] On Behalf Of Peter
 Damian Jarowski peterjarowski[-]
 Sent: Monday, September 07, 2015 2:40 AM
 To: Bashford, Don
 Subject: CCL: Case Studies of QM Computational Chemistry in Reactivity
 Sent to CCL by: "Peter Damian Jarowski" [peterjarowski :]
 Dear All:
 I am looking to collect case studies of how computational chemistry
 (specifically QM) has been able to predict or refine/optimize chemical
 reactions, especially cases where experimental work has followed this
 theoretical work up to achieve higher yields or selectivity. Any references or
 descriptions would be much appreciated and I would use them to build an argument
 for QM. I would of course give references and credit and then I will share a
 report here.
 A good example would be my own work where we were able to predict the existence
 of an isolable intermediate and then prove this with experiment and XRD:
 Wu, Y.-L.; Jarowski, P. D.; Schweizer, W. B.; Diederich, F. "Mechanistic
 Investigation of the Formal [2+2] Cycloaddition-Cycloreversion Reaction between
 4-(N,N-Dimethylamino)phenylacetylene and Arylated 1,1-Dicyanovinyl Derivatives
 to Form Intramolecular Charge-Transfer Chromophores." Chem. Eur. J. 2009,
 16, 202-211.
 However, I am looking for industry relevant examples. I would love to hear from
 the community about this and I think it would benefit everyone to have at hand
 such examples.
 Best Regards,