{"id":21616,"date":"2019-12-13T17:29:37","date_gmt":"2019-12-13T17:29:37","guid":{"rendered":"https:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=21616"},"modified":"2019-12-13T17:48:26","modified_gmt":"2019-12-13T17:48:26","slug":"molecules-of-the-year-2019-the-incredible-chloride-cage","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=21616","title":{"rendered":"Molecules of the year – 2019: the incredible chloride cage."},"content":{"rendered":"
\n

Each year, C&E News runs a poll for their “Molecule of the year<\/em><\/a>“. I occasionally comment with some aspect of one of the molecules that catches my eye (I have already written<\/a> about cyclo[18]carbon, another in the list). Here, it is the Incredible chloride cage<\/strong>, a cryptand-like container with an attomolar (1017<\/sup> M-1<\/sup>) affinity for a chloride anion.[1]<\/a><\/span> The essence of the binding is six<\/strong> short CH…Cl–<\/sup> and one slightly longer interactions to the same chloride (DOI: 10.5517\/ccdc.csd.cc1ngqrl<\/a>) and one further hydrogen bond to a water molecule; eight coordinated chloride anion!<\/p>\n

\"\"

Click image for 3D model<\/p><\/div>\n

Here I thought I might explore how common the C-H…C–<\/sup> motif is in crystal structures by showing some searches of the CSD. The CH—Cl distances reported in the article are around 2.7-2.9\u00c5 and I wanted to see how these compare with other structures. The searches were done with the constraint of data collection <90K, to minimise vibrational noise and intermolecular contacts only.<\/p>\n

The first search is for all contacts to Cl, including covalent chlorine and also perchlorate anions, and you can see that they can extend down to about 2.4\u00c5, although the commonest short contact is 2.5\u00c5<\/p>\n

\"\"<\/a><\/p>\n

This second search is for chloride anion only (by excluding any higher coordination at that atom), and the distribution does not really change.<\/p>\n

\"\"<\/a><\/p>\n

This final search is for any chloride anion with at least THREE CH…Cl contacts to the same atom and now you are seeing ~2.7\u00c5 as the commonest short contact, which corresponds exactly with the molecule reported above.<\/p>\n

\"\"<\/a><\/p>\n

So the apparently weak CH…Cl hydrogen bond, if there are seven of them, can accumulate to give attomolar binding affinities. Wow, imagine a drug with that sort of affinity!<\/p>\n

References<\/h2>\n
  1. Y. Liu, W. Zhao, C. Chen, and A.H. Flood, \"Chloride capture using a C\u2013H hydrogen-bonding cage\", Science<\/i>, vol. 365, pp. 159-161, 2019. https:\/\/doi.org\/10.1126\/science.aaw5145<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    Each year, C&E News runs a poll for their “Molecule of the year“. I occasionally comment with some aspect of one of the molecules that catches my eye (I have already written about cyclo[18]carbon, another in the list). Here, it is the Incredible chloride cage, a cryptand-like container with an attomolar (1017 M-1) affinity for […]<\/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":[4],"tags":[],"ppma_author":[2661],"class_list":["post-21616","post","type-post","status-publish","format-standard","hentry","category-interesting-chemistry"],"yoast_head":"\nMolecules of the year - 2019: the incredible chloride cage. - Henry Rzepa'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=21616\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Molecules of the year - 2019: the incredible chloride cage. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"Each year, C&E News runs a poll for their “Molecule of the year“. 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The hypothesis of ion pairs in which a chloride anion is partnered by a carbocation long ago entered the standard textbooks\u2026","rel":"","context":"In "Interesting chemistry"","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\/05\/isobornyl.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":26272,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=26272","url_meta":{"origin":21616,"position":3},"title":"Pre-mechanism for the Swern Oxidation: formation of chlorodimethylsulfonium chloride.","author":"Henry Rzepa","date":"August 25, 2023","format":false,"excerpt":"The Swern oxidation is a class of \"activated\" dimethyl sulfoxide (DMSO) reaction in which the active species is a chlorodimethylsulfonium chloride salt. The mechanism of this transformation as shown in e.g. Wikipedia is illustrated below.\u2021 However, an interesting and important aspect of chemistry is not apparent in this schematic mechanism\u2026","rel":"","context":"In "Curly arrows"","block_context":{"text":"Curly arrows","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=2327"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":63,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=63","url_meta":{"origin":21616,"position":4},"title":"The SN-1 Reaction live!","author":"Henry Rzepa","date":"April 3, 2009","format":false,"excerpt":"The ionization of a C-X bond (X=halogen) to form what we call a carbocation and which is known as the SN-1 reaction goes way back in the history of chemistry. Julius Steglitz was probably the first person to suggest such an ionization, back in 1899 (Steglitz, J.; Am. Chem. 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The explanation given in their article (p 805) confines itself to succinctly stating that only loss of the endo\u2026","rel":"","context":"In "Interesting chemistry"","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\/12\/cpendo.gif?resize=350%2C200","width":350,"height":200},"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\/21616","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=21616"}],"version-history":[{"count":8,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/21616\/revisions"}],"predecessor-version":[{"id":21630,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/21616\/revisions\/21630"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=21616"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=21616"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=21616"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=21616"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}