{"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_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":[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":28233,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=28233","url_meta":{"origin":12224,"position":5},"title":"Molecules of the Year 2024: Molecular shuttle in a box.","author":"Henry Rzepa","date":"January 25, 2025","format":false,"excerpt":"This is another in the C&E News list of candidates for the Molecule of the Year, Molecular shuttle in a box Mirror-image cyclodextrin Molecular shuttle in a box Rule-bending strained alkene First soluble promethium complex Single-electron carbon-carbon bond Hot MOF for capturing carbon The molecule shown below inside the cavity\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":"","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\/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}]}}