Guidelines for the assembly of hydrogen-bonded macrocycles.

The formation of well-defined, discrete self-assembled architectures relies on the interplay between non-covalent interactions and cooperative phenomena. In particular, chelate or intramolecular cooperativity is responsible for the assembly of closed, cyclic structures in competition with open, linear oligomers, and it can be enhanced in several ways to increase the stability of a given cycle size. In this article, we review the work of several researchers on the synthesis of hydrogen-bonded macrocycles from ditopic molecules and analyze the main factors, often interrelated, that influence the equilibrium between ring and chain species. Emphasis will be set on the diverse features that can increase cyclization fidelity, including monomer geometry, template effects, conformational effects, intramolecular interactions and H-bonding pattern.

Dye-conjugated complementary lipophilic nucleosides as useful probes to study association processes by fluorescence resonance energy transfer.

Modern supramolecular chemistry relies on the combination of diverse analytical techniques that can provide complementary information on complex self-assembly landscapes. Among them, resonance energy transfer, monitored by fluorescence emission spectroscopy, arises as a sensitive and convenient phenomenon to report binding intermolecular interactions. The use of molecular probes labelled with suitable complementary energy-transfer pairs can provide valuable information about the thermodynamics, kinetics and self-sorting characteristics of a particular self-assembled system. The objective of this work is to generate a set of nucleoside FRET probes that can be reliably employed to prove and analyse quantitatively H-bonding interactions between complementary Watson-Crick pairs. We first describe the preparation of a set of lipophilic nucleosides that are linked to a π-conjugated functional fragment. The bases include guanosine and 2-aminoadenosine as purine heterocycles, and cytidine and uridine as complementary pyrimidine bases. The π-conjugated moiety comprises either a short phenylene-ethynylene oligomer, a bithiophene, or a BODIPY dye. We then demonstrate that the last two chromophores constitute an energy donor-acceptor couple and that donor emission quenching can be related to the ratio of molecules bound to the complementary acceptor pair. Hence, fluorescence spectroscopy in combination with resonance energy transfer, is shown here to be a useful tool to study and quantify the association and self-sorting events between complementary and non-complementary nucleosides in apolar aromatic solvents, where the binding strength is considerably high, and sensitive techniques that employ low concentrations are demanded.

Synthesis and complementary self-association of novel lipophilic π-conjugated nucleoside oligomers.

A series of lipophilic nucleosides comprising natural and non-natural bases that are π-conjugated to a short oligophenylene-ethynylene fragment has been synthesized. These bases comprise guanosine, isoguanosine, and 2-aminoadenosine as purine heterocycles, and cytidine, isocytosine and uridine as complementary pyrimidine bases. The hydrogen-bonding dimerization and association processes between complementary bases were also studied by (1)H NMR and absorption spectroscopy in order to obtain the relevant association constants.