{{short description|American chemist and academic}} {{Infobox academic | name = John P. Richard | image = | birth_date = | birth_place = | nationality = | occupation = [[Chemist]] and academic | title = | awards = <!--notable national-level awards only--> | website = | education = B.S., [[Biochemistry]] (1974)<br>Ph.D., [[Chemistry]] (1979) | alma_mater = [[Ohio State University]] | thesis_title = | thesis_url = | thesis_year = | workplaces = [[University at Buffalo]], SUNY }} '''John P. Richard''' is a [[chemist]] and academic. He is a SUNY Distinguished Professor at the [[University at Buffalo]].<ref name=rip>{{Cite web|url=https://arts-sciences.buffalo.edu/college/faculty-staff/faculty-achievements.host.html/content/shared/arts-sciences/cas-shared/faculty-achievement/2019/SUNY-distinguished-professors-named.detail.html|title=Faculty Achievements|website=arts-sciences.buffalo.edu}}</ref>
Richard has studied problems related to the mechanisms for [[organic reaction]]s and their catalysis by enzymes, and has worked to test different theories to explain how [[enzyme]]s achieve their rate accelerations.<ref name=rer>{{Cite web|url=https://arts-sciences.buffalo.edu/chemistry/faculty/faculty-directory/richard.html|title=John P. Richard|website=arts-sciences.buffalo.edu}}</ref> He has edited or co-edited 17 books and has published more than 250 articles and book chapters on his research. He is the recipient of the numerous awards, including UB Sustained Achievement Award,<ref>{{Cite web|url=https://www.buffalo.edu/celebration-of-academic-excellence/FacultyStaffExcellence/PreviousFacultyStaffExcellence/ub-awards/exceptional-scholars/sustained-achievement.html|title=Sustained Achievement Award|website=www.buffalo.edu}}</ref> Jacob Schoellkopf Medal,<ref name=ygc>{{Cite web|url=https://wnyacs.files.wordpress.com/2019/08/schoellkhist.pdf|title=THE JACOB F. SCHOELLKOPF Medal 1931 -- 2019}}</ref><ref name=edu>{{Cite web|url=https://www.ubmd.com/about-ubmd/news.host.html/content/shared/university/news/news-center-releases/2009/10/10571.detail.html|title=UB Professor to Receive 2009 Schoellkopf Award|website=www.ubmd.com}}</ref> and [[National Institutes of Health|NIH]] MIRA Award.<ref name=murr>{{Cite web|url=https://arts-sciences.buffalo.edu/news-and-events/recent-news/2020/january/richard-mira-grant.html|title=UB chemist awarded $2 million NIH grant|website=arts-sciences.buffalo.edu}}</ref>
Richard is a Fellow of the [[American Chemical Society]] (ACS),<ref name=acc>{{Cite web|url=https://www.acs.org/funding/awards/acs-fellows/fellows.html|title=ACS Fellows|website=American Chemical Society}}</ref> and was Secretary of the ACS Division of Biological Chemistry from 2003 to 2008.
==Education and early career== Richard earned his B.S. degree in biochemistry from The [[Ohio State University]] in 1974. He pursued his graduate studies at the same university, working with [[Perry A. Frey]].<ref>{{Cite web|url=https://academictree.org/chemistry/peopleinfo.php?pid=67139|title=Chemistry Tree - Perry A. Frey|website=academictree.org}}</ref> Following this, he served as a Postdoctoral Fellow with [[William Jencks]] at [[Brandeis University]] from 1979 to 1982.<ref name=edu/>
==Career== Richard began his academic career in 1985 as an assistant professor in the [[University of Kentucky]], where he was promoted to associate professor in 1990. In 1993, he joined the University at Buffalo, SUNY as an associate professor. He was promoted to Professor in 1995 and to SUNY Distinguished Professor in 2019.<ref name=rip/>
Richard served as the co-chair for [[Gordon Research Conferences|GRC]] on Enzymes, Coenzymes & Metabolic Pathways in 2006,<ref>{{Cite web|url=https://www.grc.org/enzymes-coenzymes-and-metabolic-pathways-conference/2006/|title=2006 Enzymes, Coenzymes and Metabolic Pathways Conference GRC|website=www.grc.org}}</ref> the Chair of the GRC on Isotopes in Biological & Chemical Sciences in 2010,<ref>{{Cite web|url=https://www.grc.org/isotopes-in-biological-and-chemical-sciences-conference/2010/|title=2010 Isotopes in Biological and Chemical Sciences Conference GRC|website=www.grc.org}}</ref> and the co-chair of the Winter Enzyme Mechanisms Conference in 2011.<ref name=edu/> He was a member of the Organizing Committee for Reaction Mechanisms VII (2005), the 12th Kyushu International Symposium on [[Physical organic chemistry|Physical Organic Chemistry]] (2009), and the Winter Enzyme Mechanisms Conferences in 2015 and 2017.<ref>{{Cite web|url=https://www.suny.edu/about/leadership/board-of-trustees/meetings/webcastdocs/Tab04_Distinguished%20Professor.pdf|title=MEMORANDUM - March 20, 2019 - SUNY}}</ref>
==Research== Richard has conducted parallel studies on the mechanisms for organic reactions in aqueous solution and at enzyme [[active site]]s in order to define the root causes for enzymatic rate accelerations. The focus of many of these studies has been on the characterization of the lifetimes and [[Chemical stability|thermodynamic stability]] for [[carbocation]] and [[carbanion]] intermediates of organic reactions in water and the determination of the mechanisms for their stabilization by enzyme catalysts.<ref name=aww>{{cite web|url=https://www.acsu.buffalo.edu/~jrichard/richard.html|title= John P. Richard - Richard Research Group}}</ref><ref>{{Cite web|url=https://scholar.google.com/citations?user=IJ5TpeoAAAAJ&hl=en|title=John P. Richard|website=scholar.google.com}}</ref>
===Formation and stability of carbocations and carbanions in water=== Richard's postdoctoral work described the use of an azide anion clock to determine the lifetimes of carbocation intermediates of solvolysis reactions.<ref>{{cite journal |last1=Richard |first1=John P. |last2=Rothenberg |first2=Marc E. |last3=Jencks |first3=William P. |title=Formation and stability of ring-substituted 1-phenylethyl carbocations |journal=Journal of the American Chemical Society |date=March 1984 |volume=106 |issue=5 |pages=1361–1372 |doi=10.1021/ja00317a031 |bibcode=1984JAChS.106.1361R }}{{psc|date=October 2025}}</ref> He showed that these lifetimes sometimes enforce the mechanisms for [[nucleophilic substitution]] at aliphatic carbon.<ref>{{cite journal |last1=Richard |first1=John P. |last2=Jencks |first2=William P. |title=Concerted bimolecular substitution reactions of 1-phenylethyl derivatives |journal=Journal of the American Chemical Society |date=March 1984 |volume=106 |issue=5 |pages=1383–1396 |doi=10.1021/ja00317a033 |bibcode=1984JAChS.106.1383R }}{{psc|date=October 2025}}</ref><ref>{{cite journal |last1=Jencks |first1=William P. |title=When is an intermediate not an intermediate? Enforced mechanisms of general acid-base, catalyzed, carbocation, carbanion, and ligand exchange reaction |journal=Accounts of Chemical Research |date=1 June 1980 |volume=13 |issue=6 |pages=161–169 |doi=10.1021/ar50150a001 }}</ref><ref>{{cite journal |last1=Richard |first1=John P. |title=A consideration of the barrier for carbocation-nucleophile combination reactions |journal=Tetrahedron |date=February 1995 |volume=51 |issue=6 |pages=1535–1573 |doi=10.1016/0040-4020(94)01019-V }}{{psc|date=October 2025}}</ref> Richard and Amyes next reported novel methods for determination of the p''K''<sub>a</sub>s of weak carbon acids in water,<ref>{{cite journal |last1=Amyes |first1=Tina L. |last2=Richard |first2=John P. |title=Generation and stability of a simple thiol ester enolate in aqueous solution |journal=Journal of the American Chemical Society |date=December 1992 |volume=114 |issue=26 |pages=10297–10302 |doi=10.1021/ja00052a028 |bibcode=1992JAChS.11410297A }}{{psc|date=October 2025}}</ref> and their application in the determination of the effect of a spectrum of organic functional groups on carbon acid p''K''<sub>a</sub>.<ref>{{Cite journal|title=Substituent Effects on Carbon Acidity in Aqueous Solution and at Enzyme Active Sites|first1=Tina L.|last1=Amyes|first2=John P.|last2=Richard|date=July 5, 2017|journal=Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry|volume=28|issue=12|pages=2407–2421|doi=10.1055/s-0036-1588778|pmid=28993718|pmc=5630183}}</ref> His work has focused on creating a model to rationalize the large effects of resonance electron-donating or accepting substituents on the lifetimes of carbocation and carbanion intermediates of organic reactions.<ref>{{Cite journal|title=Formation and stability of carbocations and carbanions in water and intrinsic barriers to their reactions|first1=J. P.|last1=Richard|first2=T. L.|last2=Amyes|first3=M. M.|last3=Toteva|date=December 5, 2001|journal=Accounts of Chemical Research|volume=34|issue=12|pages=981–988|doi=10.1021/ar0000556|pmid=11747416}}</ref><ref>{{Cite journal|title=Intrinsic barriers to the formation and reaction of carbocations|first1=J. P.|last1=Richard|first2=T. L.|last2=Amyes|first3=K. B.|last3=Williams|date=October 30, 1998|journal=Pure and Applied Chemistry|volume=70|issue=10|pages=2007–2014|doi=10.1351/pac199870102007|doi-access=free}}</ref>
===Formation and stability of carbocations and carbanions at enzyme active sites=== Richard has worked to draw comparisons between the mechanisms for the formation of carbocations and carbanions in water and at enzyme active sites. His application of the azide ion clock to the characterization of the oxocarbocation intermediate of ß-galactosidase-catalyzed hydrolysis of lactose showed that the intermediate is stabilized by interactions with the protein catalyst.<ref>{{Cite journal|title=Structure-reactivity relationships for beta-galactosidase (Escherichia coli, lac Z). 4. Mechanism for reaction of nucleophiles with the galactosyl-enzyme intermediates of E461G and E461Q beta-galactosidases|first1=J. P.|last1=Richard|first2=R. E.|last2=Huber|first3=C.|last3=Heo|first4=T. L.|last4=Amyes|first5=S.|last5=Lin|date=September 24, 1996|journal=Biochemistry|volume=35|issue=38|pages=12387–12401|doi=10.1021/bi961029b|pmid=8823174}}</ref> His comparison of the pKas for the weakly acidic C-6 hydrogen of [[uridine]] monophosphate in water and at the active site of orotidine 5'-monophosphate decarboxylate demonstrated that there is a large stabilization of the UMP carbanion [[reaction intermediate]] by interactions with the protein catalyst.<ref>{{Cite journal|title=Proton transfer from C-6 of uridine 5'-monophosphate catalyzed by orotidine 5'-monophosphate decarboxylase: formation and stability of a vinyl carbanion intermediate and the effect of a 5-fluoro substituent|first1=Wing-Yin|last1=Tsang|first2=B. McKay|last2=Wood|first3=Freeman M.|last3=Wong|first4=Weiming|last4=Wu|first5=John A.|last5=Gerlt|first6=Tina L.|last6=Amyes|first7=John P.|last7=Richard|date=September 5, 2012|journal=Journal of the American Chemical Society|volume=134|issue=35|pages=14580–14594|doi=10.1021/ja3058474|pmid=22812629|pmc=3434256}}</ref> This was one key result from studies to characterize the mechanism of action of an enzyme that operates at peak catalytic efficiency.<ref>{{Cite journal|title=Orotidine 5'-Monophosphate Decarboxylase: Probing the Limits of the Possible for Enzyme Catalysis|first1=John P.|last1=Richard|first2=Tina L.|last2=Amyes|first3=Archie C.|last3=Reyes|date=April 17, 2018|journal=Accounts of Chemical Research|volume=51|issue=4|pages=960–969|doi=10.1021/acs.accounts.8b00059|pmid=29595949|pmc=6016548}}</ref> His investigations on the glycolytic enzyme [[triosephosphate isomerase]] revealed the mechanism by which the catalyst operates to increase the driving force for proton transfer from the enzyme-bound carbon acid to the protein.<ref>{{Cite journal|title=Enzyme Architecture: Amino Acid Side-Chains That Function To Optimize the Basicity of the Active Site Glutamate of Triosephosphate Isomerase|first1=Xiang|last1=Zhai|first2=Christopher J.|last2=Reinhardt|first3=M. Merced|last3=Malabanan|first4=Tina L.|last4=Amyes|first5=John P.|last5=Richard|date=July 5, 2018|journal=Journal of the American Chemical Society|volume=140|issue=26|pages=8277–8286|doi=10.1021/jacs.8b04367|pmid=29862813|pmc=6037162 |bibcode=2018JAChS.140.8277Z }}</ref>
===Bioorganic and bioinorganic reaction mechanisms=== Richard's investigations on the nonenzymatic [[isomerization]] and elimination reactions of triosephosphates have shed light on the origin of cellular methylglyoxal, a toxic compound that is neutralized by the action of glyoxalase I and II.<ref>{{Cite journal|title=Mechanism for the formation of methylglyoxal from triosephosphates|first=J. P.|last=Richard|date=May 5, 1993|journal=Biochemical Society Transactions|volume=21|issue=2|pages=549–553|doi=10.1042/bst0210549|pmid=8359530}}</ref> His work has led to the identification of novel nonenzymatic Claisen and aldol condensation reactions of pyridoxal cofactor analogs, and results from collaborative studies with Crugeiras and Rios provide a characterization of the kinetics and thermodynamics for proton transfer reactions at pyridoxal-amino acid adducts.<ref>{{Cite journal|title=Pyridoxal 5′-phosphate: electrophilic catalyst extraordinaire|first1=John P|last1=Richard|first2=Tina L|last2=Amyes|first3=Juan|last3=Crugeiras|first4=Ana|last4=Rios|date=October 1, 2009|journal=Current Opinion in Chemical Biology|volume=13|issue=4|pages=475–483|doi=10.1016/j.cbpa.2009.06.023|pmid=19640775 |pmc=2749917}}</ref> In collaboration with Richard Nagorski, it was demonstrated that Zn<sup>2+</sup> catalyzes aldose-ketose isomerization through competing proton and hydride transfer mechanisms. This finding was predicted because the two mechanisms are followed by enzymes such as triosephosphate isomerase (proton transfer) and xylose isomerase (hydride transfer).<ref>{{Cite journal|title=Mechanistic imperatives for aldose-ketose isomerization in water: specific, general base- and metal ion-catalyzed isomerization of glyceraldehyde with proton and hydride transfer|first1=R. W.|last1=Nagorski|first2=J. P.|last2=Richard|date=February 7, 2001|journal=Journal of the American Chemical Society|volume=123|issue=5|pages=794–802|doi=10.1021/ja003433a|pmid=11456612}}</ref> Alongside Janet Morrow, Richard investigated small molecule metal-ion catalysts of phosphate diester hydrolysis in work that characterized cooperativity in catalysis by binuclear complexes and demonstrated that these complexes achieve enzyme-like rate accelerations.<ref>{{Cite journal|title=Phosphate Binding Energy and Catalysis by Small and Large Molecules|first1=Janet R.|last1=Morrow|first2=Tina L.|last2=Amyes|first3=John P.|last3=Richard|date=April 1, 2008|journal=Accounts of Chemical Research|volume=41|issue=4|pages=539–548|doi=10.1021/ar7002013|pmid=18293941|pmc=2652674}}</ref>
===Role of substrate-driven conformational changes in enzyme catalysis=== Richard and Amyes discovered that many enzyme-catalyzed reactions of phosphodianion truncated substrates are activated by phosphite dianion.<ref>{{Cite journal|title=Phosphodianion Activation of Enzymes for Catalysis of Central Metabolic Reactions|first1=Patrick L.|last1=Fernandez|first2=Richard W.|last2=Nagorski|first3=Judith R.|last3=Cristobal|first4=Tina L.|last4=Amyes|first5=John P.|last5=Richard|date=February 24, 2021|journal=Journal of the American Chemical Society|volume=143|issue=7|pages=2694–2698|doi=10.1021/jacs.0c13423|pmid=33560827|pmc=7919737 |bibcode=2021JAChS.143.2694F }}</ref><ref>{{Cite journal|title=Enabling Role of Ligand-Driven Conformational Changes in Enzyme Evolution|first=John P.|last=Richard|date=August 2, 2022|journal=Biochemistry|volume=61|issue=15|pages=1533–1542|doi=10.1021/acs.biochem.2c00178|pmid=35829700|pmc=9354746}}</ref> These enzymes utilize binding energy of the substrate phosphodianion to drive a change in protein conformation that traps the substrate at an active-site cage;<ref>{{Cite journal|title=Protein Flexibility and Stiffness Enable Efficient Enzymatic Catalysis|first=John P.|last=Richard|date=February 27, 2019|journal=Journal of the American Chemical Society|volume=141|issue=8|pages=3320–3331|doi=10.1021/jacs.8b10836|pmid=30703322|pmc=6396832 |bibcode=2019JAChS.141.3320R }}</ref> this is equivalent to the substrate-induced fits first described by Daniel Koshand.<ref>{{Cite journal|title=Application of a Theory of Enzyme Specificity to Protein Synthesis|first=D. E.|last=Koshland|date=February 5, 1958|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=44|issue=2|pages=98–104|doi=10.1073/pnas.44.2.98|doi-access=free |pmid=16590179|pmc=335371|bibcode=1958PNAS...44...98K }}</ref> The activating substrate-driven enzyme conformational changes result in the differential binding of enzymatic ground and [[transition state]]s that is a required property of the most proficient enzyme catalysts.<ref>{{Cite journal|title=Evolution of enzyme function and the development of catalytic efficiency|first1=W. J.|last1=Albery|first2=J. R.|last2=Knowles|date=December 14, 1976|journal=Biochemistry|volume=15|issue=25|pages=5631–5640|doi=10.1021/bi00670a032|pmid=999839}}</ref> This model has provided a simple rationalization for the activation of adenylate kinase-catalyzed phosphoryl group transfer from adenosine triphosphate to phosphite dianion by the substrate fragment adenosine,<ref>{{Cite journal|title=Adenylate Kinase-Catalyzed Reactions of AMP in Pieces: Specificity for Catalysis at the Nucleoside Activator and Dianion Catalytic Sites|first1=Patrick L.|last1=Fernandez|first2=John P.|last2=Richard|date=December 6, 2022|journal=Biochemistry|volume=61|issue=23|pages=2766–2775|doi=10.1021/acs.biochem.2c00531|pmid=36413937|pmc=9731266}}</ref> as well as for the activation of formate dehydrogenase-catalyzed hydride transfer from formate to nicotinamide riboside by the substrate fragment ADP.<ref>{{Cite journal|title=Utilization of Cofactor Binding Energy for Enzyme Catalysis: Formate Dehydrogenase-Catalyzed Reactions of the Whole NAD Cofactor and Cofactor Pieces|first1=Judith R.|last1=Cristobal|first2=Richard W.|last2=Nagorski|first3=John P.|last3=Richard|date=August 1, 2023|journal=Biochemistry|volume=62|issue=15|pages=2314–2324|doi=10.1021/acs.biochem.3c00290|pmid=37463347|pmc=10399567 }}</ref> The latter finding confirmed a proposal by W. P. Jencks that evolution has produced cofactors composed of small reactive functionalities connected to larger nonreactive fragments that provide large intrinsic binding energies for stabilization of enzymatic transition states.<ref>{{Cite book|chapter-url=https://onlinelibrary.wiley.com/doi/10.1002/9780470122884.ch4|chapter=Binding Energy, Specificity, and Enzymic Catalysis: The Circe Effect|first=William P.|last=Jencks|title=Advances in Enzymology and Related Areas of Molecular Biology |editor-first=Alton|editor-last=Meister|date=January 5, 1975|publisher=Wiley|volume=43|pages=219–410|via=CrossRef|doi=10.1002/9780470122884.ch4|pmid=892 |isbn=978-0-471-59178-8 }}</ref>
==Awards and honors== *2003 – Walton Visitor Fellow, University College, Dublin, Ireland<ref name=aww/> *2009 – Jacob Schoellkopf Medal, ACS Western New York Section<ref name=ygc/> *2014 – Fellow, American Chemical Society<ref name=acc/> *2020 – MIRA Award, NIH<ref name=murr/>
===Selected publications=== *Richard, J. P. (1993). Mechanism for the formation of methylglyoxal from triosephosphates. Biochemical Society Transactions, 21(2), 549–553. *Iranzo, O., Kovalevsky, A. Y., Morrow, J. R., & Richard, J. P. (2003). Physical and kinetic analysis of the cooperative role of metal ions in catalysis of phosphodiester cleavage by a dinuclear Zn (II) complex. Journal of the American Chemical Society, 125(7), 1988–1993. *Amyes, T. L., Diver, S. T., Richard, J. P., Rivas, F. M., & Toth, K. (2004). Formation and stability of N-heterocyclic carbenes in water: the carbon acid p K a of imidazolium cations in aqueous solution. Journal of the American Chemical Society, 126(13), 4366–4374. *Richard, J. P. (2019). Protein flexibility and stiffness enable efficient enzymatic catalysis. Journal of the American Chemical Society, 141(8), 3320–3331. *Richard, J. P. (2022). Enabling role of ligand-driven conformational changes in enzyme evolution. Biochemistry, 61(15), 1533–1542.
==References== {{reflist}}
{{DEFAULTSORT:Richard, John P.}} [[Category:Ohio State University alumni]] [[Category:University at Buffalo faculty]]
[[Category:Living people]]
[[Category:1950s births]] [[Category:Year of birth missing (living people)]] [[Category:University of Kentucky faculty]]
{{Improve categories|date=December 2023}} [[Category:American chemists]] [[Category:Fellows of the American Chemical Society]]