Nonpolymeric Thermosensitive Supramolecules

Abstract

Here we show 2'-deoxyguanosine derivatives that self-assemble in aqueous media into discrete supramolecular hexadecamers and exhibit the lower critical solution temperature (LCST) phenomenon. Spectroscopic, calorimetric and electron microscopy studies support the fact that above transition temperature (T t ) the supramolecules further assemble into nanoscopic spherical globules of low polydispersity. Furthermore, the T t can be tuned to higher values by the addition of a more hydrophilic derivative. These findings uncover a new paradigm in the development of smart thermosensitive materials with properties and applications complementary to those of polymers.Naturally occurring molecular machines self-assemble into a wide variety of nanostructures that are able to sense environmental changes and respond to them accordingly. Artificial stimuli responsive (i.e., smart) materials have found numerous applications in biomedicine and nanotechnology. 1 This is due to their ability to undergo large changes in a property triggered by a relatively small stimulus. In thermosensitive materials, when a water soluble substance is made increasingly hydrophobic, it will reach a range of compositions upon which it will show a lower critical solution temperature (LCST) before becoming completely insoluble. 2 Polymers represent the overwhelming majority of known substances that show the LCST phenomenon by undergoing a coil to globule transition and/or self-assembling into aggregates upon reaching a transition temperature (T t ). 1c,3,4 Thermally responsive polymers, most notably, elastin-like polypeptides (ELPs) 5 and poly(N-isopropylacrylamide) (pNIPAAm), 6 are attractive due to their suitability for fundamental studies as well as their practical uses in a plethora of applications. [7][8][9][10][11] Although in principle, non-polymeric and well-defined supramolecular assemblies could be developed to show this property, to the best of our knowledge, there are still no known examples of such substances. Here we show 2'-deoxyguanosine derivatives that self-assemble in aqueous media into discrete supramolecular hexadecamers and exhibit the LCST phenomenon. Furthermore, the T t can be tuned to higher values by the addition of a more hydrophilic jmrivortz@mac.com. Supporting Information Available: Detailed synthetic procedures, characterization for all new compounds, experimental protocols, and NMR data. This material is available free of charge via the Internet at http://pubs.acs.org. Supramolecular self-assembly offers a complementary biomimetic strategy to the use of polymers for the development of functional nanostructures. 1,12,13 Attractive features of supramolecular self-assembly include synthetic economy and the dynamic exchange of subunits. Our efforts in this field have been aimed at studying the self-assembly of 2'-deoxyguanosine derivatives, in particular, modulation of the resulting supramolecular structures by replacing H8 in the guanine moiety with a functionalized aryl group (Figure 1). 14 We have shown that the ...

Self-assembled cation transporters made from lipophilic 8-phenyl-2′-deoxyguanosine derivatives

“…Specifically, the thermodynamic stability, molecularity and fidelity of such supramolecules is influenced by parameters such as: (a) the nature and the position of the functional group at the 8-phenyl ring,14, 15 and (b) the nature and the size of the moieties attached to the 3'- and 5'-OH groups of the furanose ring 16,17. The medium, or extrinsic parameters, also influences the assembly process 18,19. For example, in organic media, and under identical conditions, the meta -acetylphenyl derivative ( mAGi ) assembles into a hexadecamer, while its para acetylphenyl isomer ( pAGi ) assembles into an octamer (Figure 1).…”

The Use of a Peptidic Scaffold for the Formation of Stable Guanine Tetrads: Control of a H‐bonded Pattern in Water

“…Interestingly, they demonstrated that the molecule is able to self-assemble in water as a result of the formation of a hexadecamer. [6] They attributed the enhanced stability to a combination of factors, including the formation of extra H bonds and increased p-stacking interactions. Nevertheless, the studies were performed by using 1 m KCl, which emphasizes the difficulties of creating hydrogen bonds between small molecules in water.…”

Probing the limits of supramolecular G-quadruplexes using atomistic molecular dynamics simulations

“…Experimentally, however, we have only identified one type of dodecamer in solution. 18, 21–22, 37, 39–40 Such experimental evidence also strongly suggests that the observed 3 T-SGQ results from the stacking of a third tetrad on a pre-existing D 4 -symmetric 2 T-SGQ. Therefore, we can deduce that the dodecamer formed must have at least one homomeric interface ( hh or tt ), which were the ones selected for further MDS studies (Scheme 1).…”

“…While we anticipate these results to be broadly general to a wide variety of SGQs made from 8ArGs, there are several outstanding questions pertaining to derivatives lacking the meta-acetylphenyl moiety. For example, we reported the propensity of a 8-(3-pyridyl)-G derivative to form dodecameric SGQs (3T–SGQs) with high fidelity, 18, 21–22, 37, 39–40 because attractive dipole-dipole interactions were enough to stabilize the supramolecular state up to that molecularity, yet, not enough to sustain a stable 4T–SGQ. But, what about other moieties and functionalities?…”

“…The lines between each node denote a relationship of ancestor/progeny where the corresponding progeny for a given ancestor is deduced by the matching symmetries of the interfaces between each pair of tetrads. The solid and dashed lines represent pathways available for experimentally observed 18, 21–22, 37, 39–40 and hypothetical SGQs, respectively. Double lines indicate that the progeny can be formed by addition of a new tetrad from either side of the parental SGQ.…”