Our last three papers…

mAGi16-Top2_whiteBelow are the references to our last three papers. I will post a brief overview of each one soon, but in the meantime:

Structural studies of supramolecular G-quadruplexes formed from 8-aryl-2’-deoxyguanosine derivatives. García-Arriaga, M.; Hobley, G.; Rivera, J. M.,  J. Org. Chem.2016, 81, Advance Online Publication; DOI: 10.1021/acs.joc.6b01113. PMID: 27303787

  • The first 50 people can download a free reprint of the paper directly from the publisher by going to this link.
  • Abstract. Self-assembly is a powerful tool for the construction of complex nanostructures. Despite the advances in the field, the development of precise self-assembled structures remains a challenge. We have shown that in the presence of suitably sized cations like K+, 8-aryl-2′-deoxyguanosine (8ArG) derivatives self-assemble into sets of coaxially stacked planar tetramers, we term supramolecular G-quadruplexes (SGQs). Previously, we reported that when the 8-aryl group is a phenyl ring with a meta-carbonyl group, the resulting supramolecule is a hexadecamer, which is remarkably robust as illustrated by its isostructural assembly in both organic and aqueous environments. We report here a detailed three-dimensional structure of the SGQs formed by lipophilic, and hydrophilic, 8ArG derivatives with either 8-(meta-acetylphenyl), 8-(para-acetylphenyl), and 8-(meta-ethoxycarbonylphenyl) groups. The chirality and close contacts between the subunits impose different levels of steric and electrostatic constraints on opposite sides of the tetrads, which determine their preferred relative orientation. The balance between attractive non-covalent interactions juxtaposed with repulsive steric and electrostatic interactions explains the high cooperativity, fidelity and stability of these SGQs. These structural studies, together with titration experiments and molecular dynamics simulations provide insight on the mechanism of formation of these SGQs.

Organic Nanoflowers From a Wide Variety of Molecules Templated By A Hierarchical Supramolecular Scaffold. Negrón, L. M.; Diaz, T. L.; Ortiz-Quiles, E. O.; Dieppa, D.; Madera-Soto, B.; Rivera, J. M., Langmuir 2016, 32 (10), 2283–2290. DOI: 10.1021/acs.langmuir.5b03946; PMCID: PMC4896646

  • Abstract. Nanoflowers (NFs) are flowered-shaped particles with overall sizes or features in the nanoscale. Beyond their pleasing aesthetics, NFs have found a number of applications ranging from catalysis, to sensing, to drug delivery. Compared to inorganic based NFs, their organic and hybrid counterparts are relatively underdeveloped mostly because of the lack of a reliable and versatile method for their construction. We report here a method for constructing NFs from a wide variety of biologically relevant molecules (guests), ranging from small molecules, like doxorubicin, to biomacromolecules, like various proteins and plasmid DNA. The method relies on the encapsulation of the guests within a hierarchically structured particle made from supramolecular G-quadruplexes. The size and overall flexibility of the guests dictate the broad morphological features of the resulting NFs, specifically, small and rigid guests favor the formation of NFs with spiky petals, while large and/or flexible guests promote NFs with wide petals. The results from experiments using confocal fluorescence microscopy, and scanning electron microscopy provides the basis for the proposed mechanism for the NF formation.

Tuning Thermoresponsive Supramolecular G-Quadruplexes. José E. Betancourt & José M. Rivera, Langmuir 2015, 31 (7), 2095-2103. DOI:10.1021/la504446k; PMCID: PMC4863471 [Free PMC Article]

  • 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.

Exploring the periodic table with supramolecular G-quadruplexes



Our latest article just came out on the web: Tuning supramolecular G-quadruplexes with mono- and divalent cations (Mariana Martín-Hidalgo, Marilyn García-Arriaga, Fernando González, José M. Rivera,  Supramolecular Chemistry, DOI: 10.1080/10610278.2014.924626) In it we describe a series of systematic studies of the effect of a series of cations on the structure and other properties of supramolecular G-quadruplexes. You can download a free (!) copy of the article here, but you better hurry as this is a limited time offer available only to the first 50 people to take advantage of it. If, however, you are not one of the “50 lucky winners”, don’t despair, you can still get a copy article by simply leaving a request in the comments. In the meantime, here’s the abstract:

Supramolecular G-quadruplexes (SGQs) are formed via the cation promoted self-assembly of guanine derivatives into stacks of planar hydrogen-bonded tetramers. Here, we present results on the formation of SGQs made from the 8-(m-acetylphenyl)-2′-deoxyguanosine (mAGi) derivative in the presence of various mono- and divalent cations. NMR and HR ESI-MS data indicate that varying the cation can efficiently tune the molecularity, the fidelity and stability (thermal and kinetic) of the resulting SGQs. The results show that, parallel to the previously reported potassium-templated hexadecamer (mAGi16·3K+), Na+, Rb+and NH4+ also promote the formation of similar supramolecules with high fidelity and molecularity. In contrast, the divalent cations Pb2+, Sr2+ and Ba2+ template the formation of octamers (mAGi8), with the latter two inducing higher thermal stabilities. Molecular dynamics simulations for the hexadecamers containing monovalent cations enabled critical insights that help explain the experimental observations.


The phoenix finally rises from the ashes…


Every research paper is special and it’s the source of great satisfaction when it finally gets published. Seeing our latest article “A Photoresponsive Supramolecular G-Quadruplex” finally published is particularly satisfying because of the long arduous road to publication. Our internal code name for this manuscript was “Phoenix” because of the parallel between the mythical beast (burning down and raising from the ashes) and the supramolecule described in the article, which is destroyed after photoirradiation and eventually leads to a new (heteromeric) supramolecule to rise from the ashes. What we didn’t know the first time we submitted this work for publication was that the manuscript would ended up being “burned down to ashes” by the referees at multiple journals before finally raising for good. The whole process was very humbling and tested our character, but in the end, the final product was a much refined piece of work for which we should be proud of. And now, to continue writing with the hope that our next submissions don’t have to travel such a rough path.