The search for supramolecular catalysis using supramolecular guanine quadruplexes

Organic synthesis was used to construct monomeric dG subunits that further self-assembled into discrete hexadecamers and used as the skeleton for building up multi-component and functional structures. We explored the self-assembly and photophysical properties of two different C8 aryl dG derivatives: the earlier described mAG derivatives in its cationic and dendritic form, and a PyrmAG scaffold made by attaching a pyrenyl group to the 4-acetyl of mAG. The behavior of mAGa and PyrmAGa mixed at different ratio is presented. Lastly, the assembly of a peroxidative mAG16-hemin complex using hydrophilic mAG derivatives is described. All investigations presented here used mAG as common intermediate in the synthesis.;We studied PyrmAGa alone and mixed with mAGa in organic solvents and also studied three hydrophilic mAG derivatives in aqueous media. The summary of the results are: 1) it is not possible to have a clear cutoff for monomeric and excimeric entities, 2) a large Stock shifts is observed, 3) after assembly a bathochromic shift and hypochromic effects were measured, 4) PyrmAGa self-assembled into a hexadecamer in CHCl3 and in MeCN with up to 15% DMSO, 5) PyrmAGa those not formed an assembly with Na+ under the same conditions that K+ templates the formation of the hexadecamer, 6) a 21-mer of PyrmAGa derivative was observed in the gas phase, 7) when different scaffolds are mixed, if the key information at 4-acetyl phenyl is preserved, a non-narcissistic arrangement will be observed, 8) upon titration of mAGa with PyrmAGa no homomeric assembly PyrmAGa was observed by TOF-MS and by NMR, 9) mAG can be used to construct SAD of 39-kDa, and 10) some SGQs can enhanced ABTS oxidation when mixed with hemin and peroxide. Using a combination of mass spectrometry, spectroscopic and fluorescence techniques we evolve the mAG scaffold into a fluorescent scaffold asset by the reactivity of the 8-aryl-acetyl functionality. The new fluorescent scaffold (PyrmAGa) of large Stocks shift was further assembled into a hexadecameric dye, producing a red-shifted but quenched emission after the addition of 0.5 eq. KSCN. The emission of the assembly was enhanced by mixing mAGa and PyrmAGa in proportion of one per each sixteen (1.0 to 0.063). We attempt to characterize the mixture of assemblies of mAGa / PyrmAGa at different ratios even by 13C enriched mAGa at the 3' and 5' acetyl groups. Although, It was not possible to identified how is the mixture distributed but there are tendencies that makes it similar to a non-integrated self-sorting since the mixtures of contains no homomeric PyrmAGa assemblies.;In these investigations five pre-existing observations are challenged, they are: 1) the assembly behavior of mAG with extra information at the C8 in the form of pi extended surface was unknown, 2) 2-15% DMSO prevent assembly formation, 3) if hexadecamer is formed by K+ templation then Na+ should organize the structure in at least an octamer, 4) having a pyrenyl moiety will produce a clear difference for the excimeric and monomeric emission upon addition of K+ to template assembly, and 5) the assembly outcome of the mixing of two different dG derivatives with permutation at recognition motif was also unknown (non-narcissistic sorting).;The two chapters on dyes were made in organic solvents while the second half of the investigations presented in this thesis are studies in aqueous buffer. The studies were focused in the synthesis and self-assembly of a dendrimer that resembles a globular protein. Consequently, a family of hydrophilic mAG derivatives was further used as host for a hemin guest. Some of these surprising results are: 1) the branching dendrimer of generation 4 do not prevents mAG from assembly into a hexadecamer, 2) it was possible to assemble mAG under physiological condition where salt concentrations was lower than 3 M in K+ salt, this observation has to be overcome in order to perform kinetic measurements, and 3) a larger area in the assembly of an "apoenzyme" will increase reaction rate more than dendritic generation of smaller volume and surface area.;For the first time the derivatives mAGcat, mAGD1OH and mAGD4OH self-assembled at micromolar concentrations and under physiological relevant matrix of: 600 &mgr;M derivative, only 100 mM KCl, 0.05% Triton X-100, 2% DMSO at pH 7.0 in TrisPTS or hepesKOH buffer. The melting temperatures of the supramolecules and host-guest complexes in aqueous solutions were measured using DSC. When performing assembly in organic solvents the 1H NMR was the preferred method.;Both monomers and supramolecular structure were studied mainly by NMR techniques and TOF-MS techniques. The fluorescent supramolecules were studied by steady state fluorescence and UV-vis measurements. The studies in biological media include: 1H NMR, DLS, DSC, UV-Vis and all studies were supported with construction and minimization of molecular models using Maestro. This thesis opens the window to continue growing a heteromeric hexadecamer of higher complexity where a pyrenyl dye is added in a ratio of 1 to 0.063 for having higher fluorescent response. A fluorescent antenna between a heteromeric SGQdye and a porphyrin acceptor can be made. The last finding opens the window for research in aqueous catalysis using porphyrin as active cofactor. The reaction acceleration of different substrates can be made to test specificity and asymmetric induction should be also test to take advantage of the supramolecular chirality.