Towards quantifying the role of hydrogen bonding within amphiphile self-association and resultant aggregate formation

Abstract

The role of hydrogen bonding within aggregate formation and CMC: can these properties be predicted by low level computational modelling?

Towards the Prediction of Global Solution State Properties for Hydrogen Bonded, Self‐Associating Amphiphiles

“…Crystal structures previously obtained for 8 and 16 show hydrogen bonded self-association through the formation of urea-anion tapes, [16] whilst 1,4,15,17,28,30,31 have been shown to dimerize through (thio)urea-anion hydrogen bond formation. [16,17] In contrast, ap revious structure obtained for 7 showed hydrogen bondeds elf-association throught he formation of urea-urea hydrogen bondedt apes. [16] This demonstrates that for this sub-class of anionic-HBD amphiphile, self-association, and particularly dimerization, through hydrogenb onded( thio)urea-sulfonate complex formation is the most common self-association mode within the solid state, except when anion pair effects are found to override this motif,c ausing urea-urea hydrogen bond formation to dominate.…”

“…A full series of DLS studies conducted with 1 – 31 in DMSO at both 5.56 m m and 0.56 m m show evidence of aggregates>100 nm in diameter (see Supporting Information). However, the hydrodynamic diameter ( d H ) of the (thio)urea‐anion species obtained via the Stokes–Einstein equation24 from representative 1 H NMR DOSY studies, with 1 ( d H =1.15 nm), 4 (1.11≤ d H ≥1.12 nm), 24 (1.26≤ d H ≥1.29 nm), 27 (1.42≤ d H ≥1.43 nm) and 31 (1.61≤ d H ≥1.66 nm)17 at 55.56 m m did not show any evidence of these large aggregates. The size of aggregate obtained from both 1 H NMR DOSY and DLS should be treated as an estimate, as these methods assume that the aggregate structures are spherical, large in comparison to the coordinated solvent sphere,25 and in the case of 1 H NMR DOSY experiments maybe further complicated through the presence of fast exchange processes 26.…”

“…The presence of self-associated dimers was observed for 1-31 with the exception of 22, 25 and 30.I t is hypothesized that the urea-anion hydrogenb ondedd imer could not be stabilized for 30 because of the presence of a strong intramolecular hydrogen bond. [17] The presence of a dimer is not observedw ith 22 and 25 due to the lack of an anionic or ionizable carboxylic acid residue within the molecular structure. This means the formation of the respective conjugate base involves deprotonation of the HBD array.A sar esult the hydrogen bonded dimer cannot be supported.…”

“…[16] More recently, we have focused on the synthesis and self-associative properties for the series of intrinsically fluorescent amphiphiles 28-31. [17] We were able to provide evidence that in DMSO these compounds principallya ppear to form hydrogen bonded dimers, for which dimerization constants were determined. These hydrogen bonded dimers werea lso shown to exist in the gas phase (with the exception of 30)a nd solid state through ac ombination of high resolution electrospray mass spectrometry and single-crystal X-ray diffraction studies.…”

“…These data showedacorrelationb etween increasing strength of dimerization and ad ecrease in CMC value, whichc ould be estimated through the use of low level computational modelling techniques, in a comparable but more accessible format than those predictive studies conducted by Nagarajan and Ruckenstein. [18] Herein, we widen the scopeo fo ur preliminary work [17] to include 39 structurally related compounds. This study not only verifiesa nd extends our originalh ypothesis but has enabled us to improve our predictive modelsa nd define the associated limitations.…”