From owner-chemistry@ccl.net Mon Sep 7 14:26:01 2015 From: "Bashford, Don Don.Bashford ~ stjude.org" To: CCL Subject: CCL: Case Studies of QM Computational Chemistry in Reactivity Message-Id: <-51671-150907132323-1642-LpmIF9Lb//q20pS20iy1gA:_:server.ccl.net> X-Original-From: "Bashford, Don" Content-Language: en-US Content-Transfer-Encoding: 8bit Content-Type: text/plain; charset="us-ascii" Date: Mon, 7 Sep 2015 17:23:14 +0000 MIME-Version: 1.0 Sent to CCL by: "Bashford, Don" [Don.Bashford^_^stjude.org] 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: owner-chemistry+don.bashford==stjude.org^ccl.net [mailto:owner-chemistry+don.bashford==stjude.org^ccl.net] On Behalf Of Peter Damian Jarowski peterjarowski[-]gmail.com 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 : gmail.com] 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, Peterhttp://www.ccl.net/cgi-bin/ccl/send_ccl_messagehttp://www.ccl.net/chemistry/sub_unsub.shtmlhttp://www.ccl.net/spammers.txt