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

Abstract

Through this extensive structure–property study we show that critical micelle concentration correlates with self‐associative hydrogen bond complex formation constant, when combined with outputs from low level, widely accessible, computational models. Herein, we bring together a series of 39 structurally related molecules related by stepwise variation of a hydrogen bond donor–acceptor amphiphilic salt. The self‐associative and corresponding global properties for this family of compounds have been studied in the gas, solid and solution states. Within the solution state, we have shown the type of self‐associated structure present to be solvent dependent. In DMSO, this class of compound show a preference for hydrogen bonded dimer formation, however moving into aqueous solutions the same compounds are found to form larger self‐associated aggregates. This observation has allowed us the unique opportunity to investigate and begin to predict self‐association events at both the molecular and extended aggregate level.

Towards the Application of Supramolecular Self-Associating Amphiphiles as Next-Generation Delivery Vehicles

“…Previously published high resolution electrospray ionisation (ESI) mass spectrometry studies have shown the anionic portion of most SSAs to exist as dimeric species [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Data previously obtained for SSAs 1 [ 16 ], 2 [ 21 ] and 4 [ 18 ] confirmed the presence of SSA anionic dimers under these experimental conditions.…”

“…To date, a library of >50 SSAs and structurally related compounds have been synthesized. The self-associative properties of this compound library and any resultant aggregate structure have also been characterised, using a variety of complementary experimental techniques ( Figure 1 ) [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. A series of solid state, single crystal X-ray diffraction studies have shown the intermolecular binding mode adopted by the anionic component of an SSA to be cation dependent [ 17 ].…”

“…However, in an aqueous environment, the SSA monomeric units have been shown to form spherical aggregates, with hydrodynamic diameters of c.a. 100–550 nm in size [ 18 , 20 ] and/or hydrogels [ 23 ].…”

Thiourea and Guanidine Compounds and Their Iridium Complexes in Drug‐Resistant Cancer Cell Lines: Structure‐Activity Relationships and Direct Luminescent Imaging

“…Compared to guanidines, thioureas are found more rarely, for example in 2‐thiouridine in tRNAs . Within chemistry, interest has centred on their hydrogen bonding capability which has enabled sensing of anions, self‐assembly, and organocatalysis, for example. The thiourea functional group has been used widely in medicine, with 2‐thiouracil itself used to treat thyroid disorders for some time .…”

Thiourea and Guanidine Compounds and their Iridium Complexes in Drug-Resistant Cancer Cell Lines: Structure-Activity Relationships and Direct Luminescent Imaging

“…Compared to guanidines, thioureas are found more rarely, for example in 2-thiouridine in tRNAs. 16 Within chemistry, interest has centred on their hydrogen bonding capability which has enabled sensing of anions, 17 self-assembly, 18 and organocatalysis, 19 for example. The thiourea functional group has been used widely in medicine, with 2-thiouracil itself used to treat thyroid disorders for some time.…”