{"id":24410,"date":"2021-11-13T16:41:01","date_gmt":"2021-11-13T16:41:01","guid":{"rendered":"https:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=24410"},"modified":"2021-11-17T08:05:13","modified_gmt":"2021-11-17T08:05:13","slug":"first-came-molnupiravir-now-there-is-paxlovid-as-a-sars-cov-2-protease-inhibitor","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410","title":{"rendered":"First came Molnupiravir &#8211; now there is Paxlovid as a SARS-CoV-2 protease inhibitor. An NCI analysis of the ligand."},"content":{"rendered":"<div class=\"kcite-section\" kcite-section-id=\"24410\">\n<p>Earlier this year, <a href=\"https:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=23410\">Molnupiravir<\/a> hit the headlines as a promising antiviral drug. This is now followed by <a href=\"https:\/\/www.science.org\/content\/blog-post\/pfizer-s-good-news-world-s-good-news\">Paxlovid<\/a>, which is the first small molecule to be aimed by design at the SAR-CoV-2 protein and which is reported as reducing greatly the risk of hospitalization or death when given within three days of symptoms appearing in high risk patients.<\/p>\n<p><a href=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid.svg\"><img decoding=\"async\" class=\"aligncenter size-large wp-image-24412\" src=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid.svg\" alt=\"\" width=\"300\" \/><\/a><\/p>\n<p>The Wikipedia page (first created in 2021) <a href=\"https:\/\/en.wikipedia.org\/wiki\/PF-07321332\"> will display a pretty good JSmol 3D model<\/a> of this; the coordinates being generated automatically on the fly from a SMILES string, which specifies only what atoms are connected in the structure by bonds.\u00a0Given that the structure of this molecule as embedded in the SARS-CoV-2 main protease<span id=\"cite_ITEM-24410-0\" name=\"citation\"><a href=\"#ITEM-24410-0\">[1]<\/a><\/span> has been determined (and can be viewed <a href=\"https:\/\/www.rcsb.org\/3d-view\/jsmol\/7vh8\" target=\"new\" rel=\"noopener\">here<\/a>),\u00a0I thought I might display those coordinates as an alternative to the Wikipedia\/JSmol generated structure.<\/p>\n<div id=\"attachment_24414\" style=\"width: 410px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-24414\" class=\"size-large wp-image-24414\" onclick=\"jmolApplet([400,400],'load wp-content\/uploads\/2021\/11\/paxlovid-H.mol2;measure 14 61;spin 3;','c2');\" src=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid-1024x923.jpg\" alt=\"\" width=\"400\" height=\"406\" \/><p id=\"caption-attachment-24414\" class=\"wp-caption-text\">Click to get 3D model<\/p><\/div>\n<p>I extracted the ligand from the PDF file and then added hydrogens manually to obtain the above result.<sup>&Dagger;<\/sup> There are two noteworthy points about these representations:<\/p>\n<ol>\n<li>A mystery concerns the nominal C\u2261N group on the top right, which displays an angle at the carbon of 117\u00b0. A cyano group is of course linear (180\u00b0). This is not a defect of the crystal structure determination, but an indication of a rather stronger interaction occurring (as indeed noted<span id=\"cite_ITEM-24410-0\" name=\"citation\"><a href=\"#ITEM-24410-0\">[1]<\/a><\/span>). The distance between the carbon of the cyano group and an adjacent sulfur is 1.814&Aring;, which indicates a covalent bond has formed to the cyano group. The nitrogen of the erstwhile cyano group is 3.013&Aring; away from an adjacent NH group, which suggests it is stabilised by a hydrogen bond.<\/li>\n<li>Crystal structure searching of units with S&#8230;C&#8230;N  in which the N has only one bond reveals zero hits, but searches of S&#8230;C&#8230;NH reveal nine hits, with S&#8230;C distances in the range 1.74 &#8211; 1.80&Aring; and C&#8230;N distances in the region 1.25-1.27&#038;Aring. The reported CN distance is 1.251&#038;ARing, confirming that when bound to the protein, the cyano group is replaced by an S-C=NH group and hence is clearly an important component of the mode of action of Paxlovid.<br \/>\n<a href=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/Screenshot-938.jpg\"><img decoding=\"async\" src=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/Screenshot-938.jpg\" alt=\"\" width=\"400\" class=\"aligncenter size-large wp-image-24438\" srcset=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/Screenshot-938.jpg 1870w, https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/Screenshot-938-300x144.jpg 300w, https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/Screenshot-938-1024x492.jpg 1024w, https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/Screenshot-938-768x369.jpg 768w, https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/Screenshot-938-1536x738.jpg 1536w\" sizes=\"(max-width: 1870px) 100vw, 1870px\" \/><\/a>\n\t<\/li>\n<li>The conformation of Paxlovid is in one respect not fully represented by the\u00a0<a href=\"https:\/\/en.wikipedia.org\/wiki\/PF-07321332\">Wikipedia diagram<\/a>, as shown below. This implies the <strong>t-butyl<\/strong> group (on the left) as being well separated from the <strong>pyrrolidinone<\/strong> ring system at the right of the molecule.<br \/>\n<img decoding=\"async\" class=\"aligncenter size-large wp-image-24416\" src=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/PF-07321332.svg\" alt=\"\" width=\"300\" \/><br \/>\nIn fact the two groups are adjacent, being held in that conformation by probably a combination of weak dispersion forces and a contribution from the surrounding protein in the crystal structure. This is more graphically shown by the NCI (non-covalent-interaction) diagram below (DOI: <a href=\"https:\/\/doi.org\/10.14469\/hpc\/9964\" rel=\"noopener\" target=\"_blank\">10.14469\/hpc\/9964<\/a>), where the green areas in the region between the two groups (ringed in red) represent stabilising interactions between them. You might also spot other green\/cyan regions indicating additional weak hydrogen bonds between C-H groups and oxygen!<\/li>\n<\/ol>\n<div id=\"attachment_24423\" style=\"width: 454px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-24423\" class=\"size-full wp-image-24423\" onclick=\"jmolApplet([450,450],'load wp-content\/uploads\/2021\/11\/paxlovid.xyz;isosurface wp-content\/uploads\/2021\/11\/paxlovid.jvxl;measure 14 61;spin 2;','c1');\" src=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid-1.jpg\" alt=\"\" width=\"444\" height=\"476\" srcset=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid-1.jpg 444w, https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid-1-280x300.jpg 280w\" sizes=\"auto, (max-width: 444px) 100vw, 444px\" \/><p id=\"caption-attachment-24423\" class=\"wp-caption-text\">PAXLOVID NCI analysis<\/p><\/div>\n<p>There are only a small number of crystal structures of small molecules containing the S-C=NH motif. I will try to find out how common this is in protein-ligand structures.<\/p>\n<hr \/>\n<p><sup>&Dagger;<\/sup> There are many tools for performing this operation. I used the following procedure. I downloaded the PDB file (<a href=\"https:\/\/files.rcsb.org\/download\/7vh8.cif\" rel=\"noopener\" target=\"_blank\">https:\/\/files.rcsb.org\/download\/7vh8.cif<\/a>), opened it in CSD Mercury, selected the ligand (by identifying the CF<sub>3<\/sub> group and clicking on one atom), inverted the selection so that everything but the ligand was then selected and using edit\/structure, I deleted the selected atoms, leaving only the ligand.<\/p>\n<h2>Postsript<\/h2>\n<p>The cyanopyrrolidine group such as in Paxlovid is well known as a specific probe.<span id=\"cite_ITEM-24410-1\" name=\"citation\"><a href=\"#ITEM-24410-1\">[2]<\/a><\/span>,<span id=\"cite_ITEM-24410-2\" name=\"citation\"><a href=\"#ITEM-24410-2\">[3]<\/a><\/span>,<span id=\"cite_ITEM-24410-3\" name=\"citation\"><a href=\"#ITEM-24410-3\">[4]<\/a><\/span> CovalentInDB is a comprehensive database facilitating the discovery of such covalent inhibitors<span id=\"cite_ITEM-24410-4\" name=\"citation\"><a href=\"#ITEM-24410-4\">[5]<\/a><\/span> and is available <a href=\"http:\/\/cadd.zju.edu.cn\/cidb\/\" target=database\">here<\/a>. There is also a program called <a href=\"https:\/\/openmolecules.org\/datawarrior\/download.html\">DataWarrior<\/a> that is potentially able to find such probes.<\/p>\n<h2>References<\/h2>\n    <ol class=\"kcite-bibliography csl-bib-body\"><li id=\"ITEM-24410-0\">Y. Zhao, C. Fang, Q. Zhang, R. Zhang, X. Zhao, Y. Duan, H. Wang, Y. Zhu, L. Feng, J. Zhao, M. Shao, X. Yang, L. Zhang, C. Peng, K. Yang, D. Ma, Z. Rao, and H. Yang, \"Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332\", <i>Protein &amp; Cell<\/i>, vol. 13, pp. 689-693, 2021. <a href=\"https:\/\/doi.org\/10.1007\/s13238-021-00883-2\">https:\/\/doi.org\/10.1007\/s13238-021-00883-2<\/a>\n\n<\/li>\n<li id=\"ITEM-24410-1\">N. Panyain, A. Godinat, A.R. Thawani, S. Lachiondo-Ortega, K. Mason, S. Elkhalifa, L.M. Smith, J.A. Harrigan, and E.W. Tate, \"Activity-based protein profiling reveals deubiquitinase and aldehyde dehydrogenase targets of a cyanopyrrolidine probe\", <i>RSC Medicinal Chemistry<\/i>, vol. 12, pp. 1935-1943, 2021. <a href=\"https:\/\/doi.org\/10.1039\/d1md00218j\">https:\/\/doi.org\/10.1039\/d1md00218j<\/a>\n\n<\/li>\n<li id=\"ITEM-24410-2\">N. Panyain, A. Godinat, T. Lanyon-Hogg, S. Lachiondo-Ortega, E.J. Will, C. Soudy, M. Mondal, K. Mason, S. Elkhalifa, L.M. Smith, J.A. Harrigan, and E.W. Tate, \"Discovery of a Potent and Selective Covalent Inhibitor and Activity-Based Probe for the Deubiquitylating Enzyme UCHL1, with Antifibrotic Activity\", <i>Journal of the American Chemical Society<\/i>, vol. 142, pp. 12020-12026, 2020. <a href=\"https:\/\/doi.org\/10.1021\/jacs.0c04527\">https:\/\/doi.org\/10.1021\/jacs.0c04527<\/a>\n\n<\/li>\n<li id=\"ITEM-24410-3\">C. Bashore, P. Jaishankar, N.J. Skelton, J. Fuhrmann, B.R. Hearn, P.S. Liu, A.R. Renslo, and E.C. Dueber, \"Cyanopyrrolidine Inhibitors of Ubiquitin Specific Protease 7 Mediate Desulfhydration of the Active-Site Cysteine\", <i>ACS Chemical Biology<\/i>, vol. 15, pp. 1392-1400, 2020. <a href=\"https:\/\/doi.org\/10.1021\/acschembio.0c00031\">https:\/\/doi.org\/10.1021\/acschembio.0c00031<\/a>\n\n<\/li>\n<li id=\"ITEM-24410-4\">H. Du, J. Gao, G. Weng, J. Ding, X. Chai, J. Pang, Y. Kang, D. Li, D. Cao, and T. Hou, \"CovalentInDB: a comprehensive database facilitating the discovery of covalent inhibitors\", <i>Nucleic Acids Research<\/i>, vol. 49, pp. D1122-D1129, 2020. <a href=\"https:\/\/doi.org\/10.1093\/nar\/gkaa876\">https:\/\/doi.org\/10.1093\/nar\/gkaa876<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> <!-- kcite-section 24410 -->","protected":false},"excerpt":{"rendered":"<p>Earlier this year, Molnupiravir hit the headlines as a promising antiviral drug. This is now followed by Paxlovid, which is the first small molecule to be aimed by design at the SAR-CoV-2 protein and which is reported as reducing greatly the risk of hospitalization or death when given within three days of symptoms appearing in [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"activitypub_content_warning":"","activitypub_content_visibility":"","activitypub_max_image_attachments":5,"activitypub_interaction_policy_quote":"anyone","activitypub_status":"","footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[2,1745,1,4],"tags":[],"ppma_author":[2661],"class_list":["post-24410","post","type-post","status-publish","format-standard","hentry","category-chemical-it","category-crystal_structure_mining","category-general","category-interesting-chemistry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>First came Molnupiravir - now there is Paxlovid as a SARS-CoV-2 protease inhibitor. An NCI analysis of the ligand. - Henry Rzepa&#039;s Blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"First came Molnupiravir - now there is Paxlovid as a SARS-CoV-2 protease inhibitor. An NCI analysis of the ligand. - Henry Rzepa&#039;s Blog\" \/>\n<meta property=\"og:description\" content=\"Earlier this year, Molnupiravir hit the headlines as a promising antiviral drug. This is now followed by Paxlovid, which is the first small molecule to be aimed by design at the SAR-CoV-2 protein and which is reported as reducing greatly the risk of hospitalization or death when given within three days of symptoms appearing in [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa&#039;s Blog\" \/>\n<meta property=\"article:published_time\" content=\"2021-11-13T16:41:01+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2021-11-17T08:05:13+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid.svg\" \/>\n<meta name=\"author\" content=\"Henry Rzepa\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Henry Rzepa\" \/>\n\t<meta name=\"twitter:label2\" content=\"Estimated reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"First came Molnupiravir - now there is Paxlovid as a SARS-CoV-2 protease inhibitor. An NCI analysis of the ligand. - Henry Rzepa&#039;s Blog","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410","og_locale":"en_GB","og_type":"article","og_title":"First came Molnupiravir - now there is Paxlovid as a SARS-CoV-2 protease inhibitor. An NCI analysis of the ligand. - Henry Rzepa&#039;s Blog","og_description":"Earlier this year, Molnupiravir hit the headlines as a promising antiviral drug. This is now followed by Paxlovid, which is the first small molecule to be aimed by design at the SAR-CoV-2 protein and which is reported as reducing greatly the risk of hospitalization or death when given within three days of symptoms appearing in [&hellip;]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410","og_site_name":"Henry Rzepa&#039;s Blog","article_published_time":"2021-11-13T16:41:01+00:00","article_modified_time":"2021-11-17T08:05:13+00:00","og_image":[{"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid.svg","type":"","width":"","height":""}],"author":"Henry Rzepa","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Henry Rzepa","Estimated reading time":"3 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"First came Molnupiravir &#8211; now there is Paxlovid as a SARS-CoV-2 protease inhibitor. An NCI analysis of the ligand.","datePublished":"2021-11-13T16:41:01+00:00","dateModified":"2021-11-17T08:05:13+00:00","mainEntityOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410"},"wordCount":667,"commentCount":2,"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410#primaryimage"},"thumbnailUrl":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid.svg","articleSection":["Chemical IT","crystal_structure_mining","General","Interesting chemistry"],"inLanguage":"en-GB","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410#respond"]}]},{"@type":"WebPage","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410","name":"First came Molnupiravir - now there is Paxlovid as a SARS-CoV-2 protease inhibitor. An NCI analysis of the ligand. - Henry Rzepa&#039;s Blog","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410#primaryimage"},"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410#primaryimage"},"thumbnailUrl":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid.svg","datePublished":"2021-11-13T16:41:01+00:00","dateModified":"2021-11-17T08:05:13+00:00","author":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"breadcrumb":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410#breadcrumb"},"inLanguage":"en-GB","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410"]}]},{"@type":"ImageObject","inLanguage":"en-GB","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410#primaryimage","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid.svg","contentUrl":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/11\/paxlovid.svg"},{"@type":"BreadcrumbList","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24410#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog"},{"@type":"ListItem","position":2,"name":"First came Molnupiravir &#8211; now there is Paxlovid as a SARS-CoV-2 protease inhibitor. An NCI analysis of the ligand."}]},{"@type":"WebSite","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#website","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/","name":"Henry Rzepa&#039;s Blog","description":"Chemistry with a twist","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-GB"},{"@type":"Person","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281","name":"Henry Rzepa","image":{"@type":"ImageObject","inLanguage":"en-GB","@id":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g370be3a7397865e4fd161aefeb0a5a85","url":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g","caption":"Henry Rzepa"},"description":"Henry Rzepa is Emeritus Professor of Computational Chemistry at Imperial College London.","sameAs":["https:\/\/orcid.org\/0000-0002-8635-8390"],"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?author=1"}]}},"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/pDef7-6lI","jetpack-related-posts":[{"id":23410,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=23410","url_meta":{"origin":24410,"position":0},"title":"The small-molecule antiviral compound Molnupiravir: an exploration of its tautomers.","author":"Henry Rzepa","date":"March 14, 2021","format":false,"excerpt":"For obvious reasons, anti-viral molecules are very much in the news at the moment. Thus Derek Lowe highlights Molnupiravir which is shown as a hydroxylamine, the representation originating from the Wikipedia page on the molecule. I like stereocentres more clearly identified using eg R\/S notation and so I went to\u2026","rel":"","context":"In &quot;Interesting chemistry&quot;","block_context":{"text":"Interesting chemistry","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=4"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/03\/molnupiravir-1024x639.jpg?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":4304,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4304","url_meta":{"origin":24410,"position":1},"title":"Hafnium and Niels Bohr","author":"Henry Rzepa","date":"June 5, 2011","format":false,"excerpt":"In 1923, Coster and von Hevesy claimed discovery of the element\u00a0Hafnium, atomic number 72 (latin Hafnia, meaning Copenhagen, where the authors worked) on the basis of six lines in its X-ray spectrum.\u00a0The debate had long raged as to whether (undiscovered) element 72 belonged to the rare-earth group 3 of the\u2026","rel":"","context":"In &quot;Chemical IT&quot;","block_context":{"text":"Chemical IT","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=2"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/06\/bohr-periodic.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":15992,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=15992","url_meta":{"origin":24410,"position":2},"title":"Celebrating Paul  Schleyer: searching for hidden treasures in the structures of metallocene complexes.","author":"Henry Rzepa","date":"April 2, 2016","format":false,"excerpt":"A celebration of the life and work of the great chemist\u00a0Paul von R. Schleyer was held this week in Erlangen, Germany. There were many fantastic talks given by some great chemists describing fascinating chemistry. Here I highlight the presentation\u00a0given by\u00a0Andy Streitwieser on the topic of organolithium chemistry, also a great\u2026","rel":"","context":"In &quot;Chemical IT&quot;","block_context":{"text":"Chemical IT","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=2"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":4814,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4814","url_meta":{"origin":24410,"position":3},"title":"Mindless chemistry or creative science?","author":"Henry Rzepa","date":"September 3, 2011","format":false,"excerpt":"The (hopefully tongue-in-cheek) title Mindless chemistry was given to an article reporting an automated stochastic search procedure for locating all possible minima with a given composition using high-level quantum mechanical calculations. \"Many new structures, often with nonintuitive geometries, were found\". Well, another approach is to follow unexpected hunches. One such\u2026","rel":"","context":"In &quot;Interesting chemistry&quot;","block_context":{"text":"Interesting chemistry","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=4"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/09\/fe2.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":22259,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22259","url_meta":{"origin":24410,"position":4},"title":"A databank of molecular dynamics reaction trajectories (DDT) focused on undergraduate teaching.","author":"Henry Rzepa","date":"April 22, 2020","format":false,"excerpt":"In a previous post, I talked about a library of reaction pathway intrinsic reaction coordinates (IRCs) containing 115 examples of organic and organometallic reactions. Now (thanks Dean!) I have been alerted to a brand new databank of dynamics trajectories (DDT), with the focus on those reactions taught in undergraduate organic\u2026","rel":"","context":"In &quot;reaction mechanism&quot;","block_context":{"text":"reaction mechanism","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1086"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2020\/04\/MD-1024x340.jpg?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":16361,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16361","url_meta":{"origin":24410,"position":5},"title":"What is the approach trajectory of enhanced (super?) nucleophiles towards a carbonyl group?","author":"Henry Rzepa","date":"May 11, 2016","format":false,"excerpt":"I have previously commented on the B\u00fcrgi\u2013Dunitz angle, this being the preferred approach trajectory of a nucleophile towards the electrophilic carbon of a carbonyl group. Some special types of nucleophile such as hydrazines (R2N-NR2) are supposed to have enhanced reactivity due to what might be described as\u00a0buttressing of adjacent lone\u2026","rel":"","context":"In &quot;Chemical IT&quot;","block_context":{"text":"Chemical IT","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=2"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]}],"jetpack_likes_enabled":false,"authors":[{"term_id":2661,"user_id":1,"is_guest":0,"slug":"admin","display_name":"Henry Rzepa","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/24410","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=24410"}],"version-history":[{"count":32,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/24410\/revisions"}],"predecessor-version":[{"id":24451,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/24410\/revisions\/24451"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=24410"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=24410"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=24410"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=24410"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}