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Homochiral oligomers with highly flexible backbones form stable H-bonded duplexes

Two homochiral building blocks featuring a protected thiol, an alkene and a H-bond recognition unit (phenol or phosphine oxide) have been prepared. Iterative photochemical thiol–ene coupling reactions were used to synthesize oligomers containing 1-4 phosphine oxide and 1-4 phenol recognition sites....

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Autores principales: Núñez-Villanueva, Diego, Hunter, Christopher A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308278/
https://www.ncbi.nlm.nih.gov/pubmed/28451167
http://dx.doi.org/10.1039/c6sc02995g
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author Núñez-Villanueva, Diego
Hunter, Christopher A.
author_facet Núñez-Villanueva, Diego
Hunter, Christopher A.
author_sort Núñez-Villanueva, Diego
collection PubMed
description Two homochiral building blocks featuring a protected thiol, an alkene and a H-bond recognition unit (phenol or phosphine oxide) have been prepared. Iterative photochemical thiol–ene coupling reactions were used to synthesize oligomers containing 1-4 phosphine oxide and 1-4 phenol recognition sites. Length-complementary H-bond donor and H-bond acceptor oligomers were found to form stable duplexes in toluene. NMR titrations and thermal denaturation experiments show that the association constant and the enthalpy of duplex formation increase significantly for every additional H-bonding unit added to the chain. There is an order of magnitude increase in stability for each additional H-bonding interaction at room temperature indicating that all of the H-bonding sites are fully bound to their complements in the duplexes. The backbone of the thiol–ene duplexes is a highly flexible alkane chain, but this conformational flexibility does not have a negative impact on binding affinity. The average effective molarity for the intramolecular H-bonding interactions that zip up the duplexes is 18 mM. This value is somewhat higher than the EM of 14 mM found for a related family of duplexes, which have the same recognition units but a more rigid backbone prepared using reductive amination chemistry. The flexible thiol–ene AAAA·DDDD duplex is an order of magnitude more stable than the rigid reductive amination AAAA·DDDD duplex. The backbone of the thiol–ene system retains much of its conformational flexibility in the duplex, and these results show that highly flexible molecules can make very stable complexes, provided there is no significant restriction of degrees of freedom on complexation.
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spelling pubmed-53082782017-04-27 Homochiral oligomers with highly flexible backbones form stable H-bonded duplexes Núñez-Villanueva, Diego Hunter, Christopher A. Chem Sci Chemistry Two homochiral building blocks featuring a protected thiol, an alkene and a H-bond recognition unit (phenol or phosphine oxide) have been prepared. Iterative photochemical thiol–ene coupling reactions were used to synthesize oligomers containing 1-4 phosphine oxide and 1-4 phenol recognition sites. Length-complementary H-bond donor and H-bond acceptor oligomers were found to form stable duplexes in toluene. NMR titrations and thermal denaturation experiments show that the association constant and the enthalpy of duplex formation increase significantly for every additional H-bonding unit added to the chain. There is an order of magnitude increase in stability for each additional H-bonding interaction at room temperature indicating that all of the H-bonding sites are fully bound to their complements in the duplexes. The backbone of the thiol–ene duplexes is a highly flexible alkane chain, but this conformational flexibility does not have a negative impact on binding affinity. The average effective molarity for the intramolecular H-bonding interactions that zip up the duplexes is 18 mM. This value is somewhat higher than the EM of 14 mM found for a related family of duplexes, which have the same recognition units but a more rigid backbone prepared using reductive amination chemistry. The flexible thiol–ene AAAA·DDDD duplex is an order of magnitude more stable than the rigid reductive amination AAAA·DDDD duplex. The backbone of the thiol–ene system retains much of its conformational flexibility in the duplex, and these results show that highly flexible molecules can make very stable complexes, provided there is no significant restriction of degrees of freedom on complexation. Royal Society of Chemistry 2017-01-01 2016-08-19 /pmc/articles/PMC5308278/ /pubmed/28451167 http://dx.doi.org/10.1039/c6sc02995g Text en This journal is © The Royal Society of Chemistry 2016 http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Núñez-Villanueva, Diego
Hunter, Christopher A.
Homochiral oligomers with highly flexible backbones form stable H-bonded duplexes
title Homochiral oligomers with highly flexible backbones form stable H-bonded duplexes
title_full Homochiral oligomers with highly flexible backbones form stable H-bonded duplexes
title_fullStr Homochiral oligomers with highly flexible backbones form stable H-bonded duplexes
title_full_unstemmed Homochiral oligomers with highly flexible backbones form stable H-bonded duplexes
title_short Homochiral oligomers with highly flexible backbones form stable H-bonded duplexes
title_sort homochiral oligomers with highly flexible backbones form stable h-bonded duplexes
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308278/
https://www.ncbi.nlm.nih.gov/pubmed/28451167
http://dx.doi.org/10.1039/c6sc02995g
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