{"id":12224,"date":"2014-04-06T08:56:44","date_gmt":"2014-04-06T07:56:44","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=12224"},"modified":"2014-04-07T14:57:34","modified_gmt":"2014-04-07T13:57:34","slug":"what-is-the-best-way-of-folding-a-straight-chain-alkane","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12224","title":{"rendered":"What is the best way of folding a straight chain alkane?"},"content":{"rendered":"
\n

In the previous post<\/a>, I showed how modelling of unbranched alkenes depended on dispersion forces. When these are included, a bent (single-hairpin) form of C58<\/sub>H118<\/sub> becomes lower in free energy than the fully extended linear form. Here I try to optimise these dispersion forces by adding further folds to see what happens.<\/p>\n

\"002\"<\/a><\/p>\n

I had noted a small kink in the bent single-hairpin form (above, red circle). What about making a full bend at that point? Such forms have been previously investigated using OPLS-AA mechanics[1]<\/a><\/span>, with the finding that such a triple-hairpin conformation (below) was 9.7 kcal\/mol higher<\/strong> in energy than the single hairpin (above). OK, its got eight gauche-turns more (four per bend, and which do cost energy), but it also has three rather than just one row of close dispersion-stabilising contacts to compensate. Using quantum rather than molecular mechanics (B3LYP+D3\/TZVP), I found that this triple-hairpin folded form was 3.2 kcal\/mol higher in free energy than the single hairpin.[2]<\/a><\/span><\/p>\n

\"Click

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

One folded at a slightly different point (below) was in fact higher 4.7 kcal\/mol in energy that the single hairpin,[3]<\/a><\/span> indicating that there is an optimum position for the bend.<\/p>\n

\"Click

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

I was convinced better folds could be found. So how about this double-hairpin, but in three dimensions to form a prism<\/strong> so that each chain has just as many contacts as the triple-hairpin, but is achieved with two-fewer gauche-turns? Its free energy[4]<\/a><\/span> is 1.6<\/del>\u00a02.5 kcal\/mol lower<\/strong> than the single-hairpin. It did not feature in the previous report[1]<\/a><\/span> and hence represents a new lowest-energy folding (the colour indicates three ribbons of attractive non-covalent interactions, using the\u00a0NCI technique). I would point out that such “manual” searching for better folds is not really sustainable; a statistical method would normally be used (MD or Monte-Carlo).<\/p>\n

\"Click

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

A similarly folded version of the triple-hairpin can be made (below), with more opportunity for five rows of close dispersion contacts. This time however, the free energy is 1.9 kcal\/mol higher than the single hairpin[5]<\/a><\/span> (but the position of the fold does need to be optimised and perhaps a better one can be found).\u00a0This result does imply that there is an optimum balance between the energy penalty of creating four gauche-turns per fold and the additional energy stabilisation of the dispersion. Perhaps the triple hair-pin above is close to that optimum?<\/p>\n

\"Click

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

Unfortunately no crystal structures for the higher linear alkanes have been reported that would give us a reality check on any of these models. Can it really be that difficult to crystallise such molecules?<\/p>\n

References<\/h2>\n
  1. L.L. Thomas, T.J. Christakis, and W.L. Jorgensen, \"Conformation of Alkanes in the Gas Phase and Pure Liquids\", The Journal of Physical Chemistry B<\/i>, vol. 110, pp. 21198-21204, 2006. https:\/\/doi.org\/10.1021\/jp064811m<\/a>\n\n<\/li>\n
  2. H.S. Rzepa, \"Gaussian Job Archive for C58H118\", 2014. https:\/\/doi.org\/10.6084\/m9.figshare.988335<\/a>\n\n<\/li>\n
  3. H.S. Rzepa, \"Gaussian Job Archive for C58H118\", 2014. https:\/\/doi.org\/10.6084\/m9.figshare.988334<\/a>\n\n<\/li>\n
  4. H.S. Rzepa, \"Gaussian Job Archive for C58H118\", 2014. https:\/\/doi.org\/10.6084\/m9.figshare.988771<\/a>\n\n<\/li>\n
  5. H.S. Rzepa, \"Gaussian Job Archive for C58H118\", 2014. https:\/\/doi.org\/10.6084\/m9.figshare.988333<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    In the previous post, I showed how modelling of unbranched alkenes depended on dispersion forces. When these are included, a bent (single-hairpin) form of C58H118 becomes lower in free energy than the fully extended linear form. Here I try to optimise these dispersion forces by adding further folds to see what happens. I had noted […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_feature_clip_id":0,"_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},"jetpack_post_was_ever_published":false},"categories":[1],"tags":[24,1198,1199,40,1197],"ppma_author":[2661],"class_list":["post-12224","post","type-post","status-publish","format-standard","hentry","category-general","tag-energy","tag-energy-penalty","tag-energy-stabilisation","tag-free-energy","tag-lowest-energy-folding"],"yoast_head":"\nWhat is the best way of folding a straight chain alkane? - 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=12224\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"What is the best way of folding a straight chain alkane? - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"In the previous post, I showed how modelling of unbranched alkenes depended on dispersion forces. When these are included, a bent (single-hairpin) form of C58H118 becomes lower in free energy than the fully extended linear form. Here I try to optimise these dispersion forces by adding further folds to see what happens. I had noted […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12224\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2014-04-06T07:56:44+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2014-04-07T13:57:34+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2014\/03\/002.jpg\" \/>\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=\"2 minutes\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"What is the best way of folding a straight chain alkane? - Henry Rzepa'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=12224","og_locale":"en_GB","og_type":"article","og_title":"What is the best way of folding a straight chain alkane? - Henry Rzepa's Blog","og_description":"In the previous post, I showed how modelling of unbranched alkenes depended on dispersion forces. When these are included, a bent (single-hairpin) form of C58H118 becomes lower in free energy than the fully extended linear form. Here I try to optimise these dispersion forces by adding further folds to see what happens. I had noted […]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12224","og_site_name":"Henry Rzepa's Blog","article_published_time":"2014-04-06T07:56:44+00:00","article_modified_time":"2014-04-07T13:57:34+00:00","og_image":[{"url":"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2014\/03\/002.jpg","type":"","width":"","height":""}],"author":"Henry Rzepa","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Henry Rzepa","Estimated reading time":"2 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12224#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12224"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"What is the best way of folding a straight chain alkane?","datePublished":"2014-04-06T07:56:44+00:00","dateModified":"2014-04-07T13:57:34+00:00","mainEntityOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12224"},"wordCount":496,"commentCount":0,"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12224#primaryimage"},"thumbnailUrl":"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2014\/03\/002.jpg","keywords":["energy","energy penalty","energy stabilisation","free energy","lowest-energy folding"],"articleSection":["General"],"inLanguage":"en-GB","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12224#respond"]}]},{"@type":"WebPage","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12224","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12224","name":"What is the best way of folding a straight chain alkane? 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Indeed, a (co-crystal) of C16H34 shows it to have two-gauche bends..\u00a0Surprisingly, the longest linear alkane I was able to find a crystal structure for, C28H58\u00a0appears to be fully extended, (an early\u2026","rel":"","context":"In "General"","block_context":{"text":"General","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":22656,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22656","url_meta":{"origin":12224,"position":1},"title":"High-performance polythioesters with high chemical recyclability.","author":"Henry Rzepa","date":"September 2, 2020","format":false,"excerpt":"Here I investigate a recent report of a new generation of polyesters with the intrinsic properties of high crystallinity and chemical recyclability. The latter point is key, since many current plastics cannot be easily recycled to a form which can be used to regenerate the original polymer with high yield.\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.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2020\/09\/RSSR-lit-1024x759.jpg?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":15671,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=15671","url_meta":{"origin":12224,"position":2},"title":"A molecular balance for dispersion energy?","author":"Henry Rzepa","date":"February 7, 2016","format":false,"excerpt":"The geometry of cyclo-octatetraenes differs fundamentally from the lower homologue benzene in exhibiting slow (nuclear) valence bond isomerism rather than rapid (electronic) bond-equalising resonance. In 1992 Anderson and Kirsch exploited this property to describe a simple molecular balance for\u00a0estimating how two alkyl substituents on the ring might interact via the\u2026","rel":"","context":"In "General"","block_context":{"text":"General","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":29725,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=29725","url_meta":{"origin":12224,"position":3},"title":"The mechanism of borohydride reductions. Part 2: 4-t-butyl-cyclohexanone – Dispersion induced stereochemistry.","author":"Henry Rzepa","date":"October 21, 2025","format":false,"excerpt":"Part one of this topic was posted more than ten years ago. I clearly forgot about it, so belatedly, here is part 2 - dealing with the stereochemistry of the reduction of tert-butyl-cyclohexanone by borohydride in water. The known stereochemistry is nicely summarised in this article, along with an extensive\u2026","rel":"","context":"In "reaction mechanism"","block_context":{"text":"reaction mechanism","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1086"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":8658,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=8658","url_meta":{"origin":12224,"position":4},"title":"Why the Sharpless epoxidation is enantioselective!","author":"Henry Rzepa","date":"December 17, 2012","format":false,"excerpt":"Part one\u00a0on this topic showed how a quantum mechanical model employing just one titanium centre was not successful in predicting the stereochemical outcome of the Sharpless asymmetric epoxidation. Here in part 2, I investigate whether a binuclear model might have more success.\u00a0The new model is constructed using two units of\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":"WAWBUR. Click for 3D","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/12\/WAWBUR.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":12115,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12115","url_meta":{"origin":12224,"position":5},"title":"Aromatic electrophilic substitution. A different light on the bromination of benzene.","author":"Henry Rzepa","date":"March 12, 2014","format":false,"excerpt":"My previous post related to the aromatic electrophilic substitution of benzene using as electrophile phenyl diazonium chloride. Another prototypical reaction, and again one where benzene is too inactive for the reaction to occur easily, is the catalyst-free bromination of benzene to give bromobenzene and HBr.\u00a0 The \"text-book\" mechanism involves nucleophilic\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":"br2+benzene","src":"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2014\/03\/br2+benzene.svg","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","author_category":"1","first_name":"Henry","last_name":"Rzepa","user_url":"https:\/\/orcid.org\/0000-0002-8635-8390","job_title":"","description":"Henry Rzepa is Emeritus Professor of Computational Chemistry at Imperial College London."}],"_links":{"self":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/12224","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=12224"}],"version-history":[{"count":26,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/12224\/revisions"}],"predecessor-version":[{"id":12259,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/12224\/revisions\/12259"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=12224"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=12224"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=12224"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=12224"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}