Tuning Thermoresponsive Supramolecular G-Quadruplexes

Abstract

Thermoresponsive systems are attractive due to their suitability for fundamental studies as well as their practical uses in a wide variety of applications. While much progress has been achieved using polymers, alternative strategies such as the use of well-defined nonpolymeric supramolecules are still underdeveloped. Here we report three 8-aryl-2′-deoxyguanosine derivatives (8ArGs) that self-assemble in aqueous media into precise thermoresponsive supramolecular G-quadruplexes (SGQs). We report the synthesis of such derivatives, studies of their isothermal self-assembly, and the thermally induced assembly to form higher-order meso-globular assemblies we term supramolecular hacky sacks (SHS). The lower critical solution temperature (LCST) that indicates the formation of the SHS was modulated by changing (a) intrinsic parameters (i.e., structure of the 8ArGs); (b) extrinsic parameters such as the salt used to promote the formation of the SGQ; and (c) supramolecular parameters such as the coassembly different 8ArGs to form heteromeric SGQs. Changes in the intrinsic parameters lead to LCST variations in the range of 28–59 °C. Modulating extrinsic parameters such as replacing KI with KSCN abolishes the thermoresponsive phenomenon whereas changing the cation from K+ to Na+ or adjusting the pH (in the range of 6–8) has negligible effects on the LCST. Modulating supramolecular parameters results in transition temperatures that are intermediate between those obtained by the respective homomeric SGQs, although the specific proportions of the subunits are critical in determining the reversibility of the process. Given the extensive applications of thermoresponsive polymers, the nonpolymeric supramolecular counterparts presented here may represent an attractive alternative for fundamental studies and biorelevant applications.

Thermoresponsive Corannulene

“…Above a solution temperature of 40 °C, the building block essentially becomes water‐insoluble and assembles to yield larger structures. Typically, such a transition is a hallmark of thermosensitive polymers, and very few small molecular motifs are known to emulate this behavior . Interestingly, during this work, we also observed a weak enhancement of emission in solution upon thermally triggered aggregation.…”

“…Typically, such a transition is a hallmark of thermosensitive polymers [22,23] and very few small molecular motifs are known to emulate this behavior. [24][25][26] Interestingly, during this work, we also observed a weak enhancement of emission in solution upon thermally triggered aggregation. In the fibrilar state, however, comparatively strong green luminescence could be seen.…”

Thermoresponsive Cellulose Acetate–Poly(N-isopropylacrylamide) Core–Shell Fibers for Controlled Capture and Release of Moisture

“…Development of smart or stimuli-responsive polymeric materials that possess the ability to change their functional properties in response to external stimuli has gathered huge amount of interest among the researchers. , Some of the external stimuli which are responsible for inducing a change in the physical or chemical properties of these smart polymers include pH, temperature, light, humidity, electric/magnetic fields, mechanical force, and the presence of small biomolecules. − Among all stimuli-responsive polymer systems, temperature-responsive polymer systems have found widespread interest as the temperature can be easily applied, externally monitored, and controlled. − …”

Enhancement of Immune Responses by Guanosine-Based Particles in DNA Plasmid Formulations against Infectious Diseases

“…G-derivative ImAG (Figure 1(a)) was synthesized and characterized as previously reported [24, 27, 28]. A solution of 0.303 mM of ImAG SGQ was warmed in a water bath at 40°C for ~3 minutes in order to promote the formation of the SHS particles and added at a final concentration of 0.1515 mM into corresponding DNA plasmid formulations (Figure 1(b)).…”

“…Here, we report the use of Supramolecular Hacky Sacks (SHS) particles, as a novel immunomodulator for DNA plasmid formulations. SHS are the resulting structure of thermo-responsive supramolecular guanosine quadruplexes (SGQs), previously reported in 2015 [24]. Guanosine and its derivatives are known to self-assemble into planar tetrameric structures [25].…”