The rate and evenness of the substitutions on hyaluronan grafted by dodecanoic acid influenced by the mixed-solvent composition

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60917431%3A_____%2F21%3AN0000002" target="_blank" >RIV/60917431:_____/21:N0000002 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/21:10438607 RIV/70883521:28110/21:63539062

Výsledek na webu

<a href="https://doi.org/10.1016/j.ijbiomac.2021.08.137" target="_blank" >https://doi.org/10.1016/j.ijbiomac.2021.08.137</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ijbiomac.2021.08.137" target="_blank" >10.1016/j.ijbiomac.2021.08.137</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The rate and evenness of the substitutions on hyaluronan grafted by dodecanoic acid influenced by the mixed-solvent composition

Popis výsledku v původním jazyce

In this work, low molecular weight (17 kDa) hyaluronan was modified by dodecanoyl substituents. The activation of dodecanoic acid was mediated by benzoyl chloride towards the preparation of a mixed anhydride, which reacts in a second step with HA in water mixed with an organic solvent. The effect of the cosolvent was studied and showed an even distribution of substituents and higher reaction rate in water: 1,4-dioxane compared to water:tert-butanol where substituents occupy adjacent positions. The chemical characterization of the prepared derivatives was elucidated by NMR, FTIR spectroscopy, thermal analyses, and gas chromatography, while the distribution of substituents was evaluated by enzymatic degradation. Molecular-dynamics simulations reveal opposite solvent separations around HA and dodecanoyl chains, that is stronger in water:tert-butanol solution. The resulting incompatibility of solvation-shells of the two entities repels the reaction intermediates from the HA chain and drives them towards the already bound substituents, explaining the observed differences in the distribution evenness. Thus, the influence of the solvent on the reaction selectivity is observed by shielding reactive sites around HA. Therefore, a control of the distribution of the substituents was obtained by defining the concentration of HA and used cosolvent.

Název v anglickém jazyce

The rate and evenness of the substitutions on hyaluronan grafted by dodecanoic acid influenced by the mixed-solvent composition

Popis výsledku anglicky

In this work, low molecular weight (17 kDa) hyaluronan was modified by dodecanoyl substituents. The activation of dodecanoic acid was mediated by benzoyl chloride towards the preparation of a mixed anhydride, which reacts in a second step with HA in water mixed with an organic solvent. The effect of the cosolvent was studied and showed an even distribution of substituents and higher reaction rate in water: 1,4-dioxane compared to water:tert-butanol where substituents occupy adjacent positions. The chemical characterization of the prepared derivatives was elucidated by NMR, FTIR spectroscopy, thermal analyses, and gas chromatography, while the distribution of substituents was evaluated by enzymatic degradation. Molecular-dynamics simulations reveal opposite solvent separations around HA and dodecanoyl chains, that is stronger in water:tert-butanol solution. The resulting incompatibility of solvation-shells of the two entities repels the reaction intermediates from the HA chain and drives them towards the already bound substituents, explaining the observed differences in the distribution evenness. Thus, the influence of the solvent on the reaction selectivity is observed by shielding reactive sites around HA. Therefore, a control of the distribution of the substituents was obtained by defining the concentration of HA and used cosolvent.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/FW01010060" target="_blank" >FW01010060: Výzkum a vývoj farmaceutické suroviny do umělých slz pro léčbu syndromu suchého oka</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

International Journal of Biological Macromolecules

ISSN

0141-8130

e-ISSN

0141-8130

Svazek periodika

189

Číslo periodika v rámci svazku

31.10.2021

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

11

Strana od-do

826-836

Kód UT WoS článku

—

EID výsledku v databázi Scopus

2-s2.0-85113981072