The use of circular dichroism spectroscopy for studying the chiral molecular self-assembly: an overview.

Self-assembly plays an important role in the formation of many chiral biological structures and in the preparation of chiral functional materials. Therefore the control of chirality in synthetic or biological self-assembled systems is important either for the comprehension of recognition phenomena or to obtain materials with predictable and controllable properties. Circular dichroism was developed to study molecular chirality, however, because of its outstanding sensitivity to chiral perturbations of the system under investigation; it has been extended more recently to supramolecular chemistry. In particular, self-assembly processes leading to the formation of chiral supramolecular architectures (and eventually to gels or liquid crystal phases) can be monitored by CD. Furthermore, CD spectroscopy often allows one to obtain structural information on the assembled structures. This review deals with representative contributions to the study of supramolecular chirality by means of circular dichroism.

Quantifying hydrogen-bonding strength: the measurement of 2hJNN couplings in self-assembled guanosines by solid-state 15N spin-echo MAS NMR.

(2h)J(NN) hydrogen-bond mediated J couplings are measured in the solid state for two synthetic deoxyguanosine derivatives by (15)N MAS NMR spin-echo experiments. The use of rotor-synchronised Hahn-echo pulse train (RS-HEPT) (1)H decoupling, with a duty cycle of 6%, allows spin-echo durations out to 200 ms, hence enabling the accurate determination of J couplings as small as 3.8 Hz. A single-crystal X-ray diffraction structure exists for the shorter alkyl chain derivative dG(C(3))(2): the observation of significantly different (2h)J(NN) couplings, 6.2 +/- 0.4 and 7.4 +/- 0.4 Hz, for the two resolved N7 resonances is to be expected given the NH...N hydrogen-bonding distances of 2.91 and 2.83 A for the two distinct molecules in the asymmetric unit cell. For the longer alkyl chain derivative, dG(C(10))(2), for which there is no single-crystal diffraction structure, a (15)N refocused INADEQUATE spectrum (Pham et al., J. Am. Chem. Soc., 2005, 127, 16018-16019) has demonstrated the presence of N2-H...N7 intermolecular hydrogen-bonds indicative of a quartet-like structure. The (2h)J(NN) hydrogen-bond mediated J coupling of 5.9 +/- 0.2 Hz is at the lower end of the range (5.9-8.2 Hz) of (2h)J(NN) couplings determined from solution-state NMR of guanosine quartets in quadruplex DNA. A full discussion of the determination of error bars on the fitted parameters is given; specifically, error bars determined by a non-linear fitting (using the covariance matrix) or in a Monte-Carlo fashion are found to give effectively identical results.

Self-assembly of an alkylated guanosine derivative into ordered supramolecular nanoribbons in solution and on solid surfaces.

We report on the synthesis and self-assembly of a guanosine derivative bearing an alkyloxy side group under different environmental conditions. This derivative was found to spontaneously form ordered supramolecular nanoribbons in which the individual nucleobases are interacting through H-bonds. In toluene and chloroform solutions the formation of gel-like liquid-crystalline phases was observed. Sub-molecularly resolved scanning tunneling microscopic imaging of monolayers physisorbed at the graphite-solution interface revealed highly ordered two-dimensional networks. The recorded intramolecular contrast can be ascribed to the electronic properties of the different moieties composing the molecule, as proven by quantum-chemical calculations. This self-assembly behavior is in excellent agreement with that of 5'-O-acylated guanosines, which are also characterized by a self-assembled motif of guanosines that resembles parallel ribbons. Therefore, for guanosine derivatives (without sterically demanding groups on the guanine base) the formation of supramolecular nanoribbons in solution, in the solid state, and on flat surfaces is universal. This result is truly important in view of the electronic properties of these supramolecular anisotropic architectures and thus for potential applications in the fields of nano- and opto-electronics.

The supramolecular helical architecture of 8-oxoinosine and 8-oxoguanosine derivatives.

The 8-oxoguanosine derivative 1 and the 8-oxoinosine derivative 2 b, with appropriate substituents on their ribose moieties, form hexagonal lyotropic mesophases in hydrocarbon solvents. Small-angle X-ray scattering analysis of a film of 1 and of the mesophase of 2 b, and NMR and CD spectra of isotropic solutions of 2 b, indicate that in both cases the supramolecular structures adopted are continuous helices formed by a hydrogen-bond network between the heterocyclic bases. Notably, while derivative 2 b, which bears large substituents on its ribose moiety, undergoes self-assembly and mesophase formation, oxoinosine 2 a, with only decanoyl groups on its ribose moiety, does not. This may be ascribed to the reduced amphiphilic properties of the latter and the absence of aromatic groups.

Homochiral helices of oligonaphthalenes inducing opposite-handed cholesteric phases.

The helical structure of the chiral nematic phases (cholesterics) obtained by doping nematic solvents with chiral non-racemic compounds is a macroscopic proof of the solute chirality. Oligonaphthalene (tetra-, hexa-, octa-) derivatives linked at the 1,4-positions have been used as chiral dopants: When the chirality axes are configurationally homogeneous (that is, all-S), the molecular structures correspond to right-handed helices. Yet, we have found series of derivatives with the surprising property that the handedness of the induced cholesteric phase alternates from positive to negative and to positive again, on passing from tetra- to hexa- and to octanaphthalene. A comparison with oligonapthalene derivatives, which do not exhibit this twisting ability, points to the importance of the substitution pattern. Both the possibility of inducing oppositely-handed cholesteric phases by homochiral helices of different length, and the role played of substituents, are confirmed by calculations performed with the surface chirality model.

A study of the stereochemistry of 2-aryl-4,5-dimethyl-1,3-dioxolanes by cholesteric induction in nematic phases and circular dichroism spectroscopy.

[Chemical reaction: See text] The circular dichroism spectra and the twisting ability of a series of 2-aryl-4,5-dimethyl-1,3-dioxolanes used as dopants in nematic solvents have been related to their absolute configuration. Whereas the circular dichroism (CD) spectra are deeply affected by the substituents present in the aromatic ring, which in several cases cause sign inversion, the helical twisting power beta is only marginally influenced. The values of beta also seem not very sensitive to the rotamer population around the aromatic ring; this indicates the predominant importance of the chiral dioxolane ring in determining the cholesteric induction. These facts can be explained by the different nature of the two observables: in CD, the chirality is read by the absorbing chromophore and is deeply influenced even by small changes of this group. In cholesteric induction we are dealing instead with chiral solute-solvent interactions that determine a twist in the solvent. In light of the present and previous results, this process seems predominantly determined by short-range interactions, which are modulated by the molecular shape. From a practical point of view, a configurational correlation using CD for the present series of compounds seems problematic, while the values of beta are nicely correlated to the absolute configurations. Calculations with the surface chirality method predict well the sign and order of magnitude of beta and their limited sensitivity to the phenyl substituents and rotamer population.

Identification by 15N refocused INADEQUATE MAS NMR of intermolecular hydrogen bonding that directs the self-assembly of modified DNA bases.

15N solid-state NMR refocused INADEQUATE spectra of two lipophilic deoxyguanosine derivatives unambiguously identify different intermolecular hydrogen-bonding arrangements that are indicative of either guanine ribbon or quartet self-assembly. The observation of guanine quartet formation in the absence of metal ions is a further example that challenges the accepted dogma that quartet formation requires metal ions.

Using diffusion NMR to characterize guanosine self-association: insights into structure and mechanism.

This paper presents results from a series of pulsed field gradient (PFG) NMR studies on lipophilic guanosine nucleosides that undergo cation-templated assembly in organic solvents. The use of PFG-NMR to measure diffusion coefficients for the different aggregates allowed us to observe the influences of cation, solvent and anion on the self-assembly process. Three case studies are presented. In the first study, diffusion NMR confirmed formation of a hexadecameric G-quadruplex [G 1](16)4 K(+)4 pic(-) in CD(3)CN. Furthermore, hexadecamer formation from 5'-TBDMS-2',3'-isopropylidene G 1 and K(+) picrate was shown to be a cooperative process in CD(3)CN. In the second study, diffusion NMR studies on 5'-(3,5-bis(methoxy)benzoyl)-2',3'-isopropylidene G 4 showed that hierarchical self-association of G(8)-octamers is controlled by the K(+) cation. Evidence for formation of both discrete G(8)-octamers and G(16)-hexadecamers in CD(2)Cl(2) was obtained. The position of this octamer-hexadecamer equilibrium was shown to depend on the K(+) concentration. In the third case, diffusion NMR was used to determine the size of a guanosine self-assembly where NMR signal integration was ambiguous. Thus, both diffusion NMR and ESI-MS show that 5'-O-acetyl-2',3'-O-isopropylidene G 7 and Na(+) picrate form a doubly charged octamer [G 7](8)2 Na(+)2 pic(-) 9 in CD(2)Cl(2). The anion's role in stabilizing this particular complex is discussed. In all three cases the information gained from the diffusion NMR technique enabled us to better understand the self-assembly processes, especially regarding the roles of cation, anion and solvent.

The control of the cholesteric pitch by some azo photochemical chiral switches.

A few chiral azo compounds, which undergo reversible photochemical switching, are presented. Of these, the most interesting contain the binaphthyl moiety and belong to the C2 (derivatives 1 and 2) or C1 symmetry group (derivatives 3 and 4). These binaphthyl compounds display intense CD and high beta values. Photochemical switching has profound effects on both the CD and beta values of these compounds; in the case of compound 3, the sign of beta changes upon isomerisation. Compound 2 has, to our knowledge, the highest beta of the switches reported in the literature and also seems the most interesting owing to its fast response to photochemical stimuli. Nematic phases can be transformed into cholesteric phases with reflection bands in the visible region by doping with reasonable amounts of 1 and 2. The reflection colours can be changed reversibly by photoisomerisation of the switches. Thermal reversion of the colourless UV photostationary state to the green isomeric EE state or to intermediate coloured states is temperature dependent. This can allow the thermal history of a sample to be traced.

The stepwise supramolecular organisation of guanosine derivatives.

Several supramolecular architectures generated by guanosine derivatives are described. The research started from the fortuitous observation of a lyotropic behavior exhibited by a guanylic nucleotide in water. This observation stimulated extensive research on several natural and lipophilic guanosine derivatives which self-assemble in different architectures (discs, ribbons, helices...), according to their structure and environment. These ordered structures can be used as scaffolds for photo- or electro-active moieties and for the fabrication of molecular electronic devices.

Supramolecular helices via self-assembly of 8-oxoguanosines.

The cooperative effect of solvophobic interactions and hydrogen bonding has been exploited to self-assemble supramolecular helical architectures of 8-oxoguanosines in different environments. This self-assembly into helical structures is completely different from that of the parent guanosines which, in the same experimental conditions, form flat, ribbonlike structures. While optical microscopy and X-ray diffraction suggest a chiral columnar aggregate in the LC phase, NMR and Circular Dichroism reveal the presence of a helical structures in solution. Scanning Tunneling Microscopy made it possible to visualize hexagonally arranged G-quartets on graphite, which are sections of the helices packed with their long axis perpendicular to the basal plane of the substrate. Due to their rectifying electrical properties, such helices are interesting for fabricating (opto)electronic biodevices.

A new axially-chiral photochemical switch.

Axially chiral bis(azo) derivative 1 undergoes photochemical isomerisation, which can be seen with circular dichroism and pitch measurements of the induced cholesteric phases.

A correlation between the absolute configuration of alkyl aryl sulfoxides and their helical twisting powers in nematic liquid crystals.

In this paper, for the first time, a systematic experimental and theoretical analysis of the cholesteric induction due to solutes whose chirality is originated only by a single stereogenic center has been carried out. The twisting power beta of a series of alkyl aryl sulfoxides has been determined in several nematic solvents. The sign of beta, which reflects the handedness of the induced helical arrangement of the solvent molecules, correlates with the configuration of the stereogenic sulfur in the nematic solvents E7, Phase 1083, and ZLI 2359: (S)-configurated dopants induce (M)-chiral nematics. (S)-Configurated cyclic sulfoxides, which are forced to adopt a different conformation with respect to the parent acyclic compounds, induce, instead, right-handed chiral nematics. The experimental data have been interpreted in the light of the surface chirality model, which allows the calculation of beta in terms of the molecular properties of the dopant, namely, the anisotropy and helicity of its molecular surface. The calculations reliably reproduce the behavior experimentally observed. The more flexible, open-chain compounds investigated induce chiral nematics of opposite handedness in MBBA and Phase 1053: temperature-dependent experiments point out the importance of the conformation in determining the effective sign of beta. The results have been discussed in terms of different conformation populations in these latter solvents with respect to E7, Phase 1083, and ZLI 2359.

Gel-like lyomesophases formed in organic solvents by self-assembled guanine ribbons.

Lipophilic guanosine derivatives are self-assembled into ribbonlike aggregates, both in the crystal state and in solution. The structure of the ribbons has been characterised by single-crystal X-ray diffraction and, in solution, by NMR spectroscopy and ESI-MS. Two different ribbons with different patterns of hydrogen bonds are present in the solid state and in chloroform solutions. The gel-like phases obtained in hexadecane, toluene and chloroform have been investigated by optical microscopy and small-angle X-ray diffraction: the type of phase observed is related to the molecular structure of the compounds and depends dramatically on the solvent. The structures of the phases are discussed, with the presence of the two different ribbons being taken into account.

Biomolecular electronic devices based on self-organized deoxyguanosine nanocrystals.

We report on a new class of hybrid electronic devices based on a DNA nucleoside (deoxyguanosine lipophilic derivative) whose assembled polymeric ribbons interconnect a submicron metallic gate. The device exhibits large conductivity at room temperature, rectifying behavior and strong current-voltage hysteresis. The transport mechanism through the molecules is investigated by comparing films with different self-assembling morphology. We found that the main transport mechanism is connected to pi-pi interactions between guanosine molecules and to the formation of a strong dipole along ribbons, consistently with the results of our first-principles calculations.

Cation-Templated Self-Assembly of a Lipophilic Deoxyguanosine: Solution Structure of a K+-dG8 Octamer.

The lipophilic nucleoside 3',5'-didecanoyl-2'-deoxyguanosine, dG 1, extracts potassium salts from water into organic solvents. The K+ extraction drives the self-association of dG 1 to give G-quartet structures. A series of 1H NMR experiments indicates that the identity of the assembled species in CDCl3 is modulated by the amount of K+ extracted by dG 1. At an 8:1 dG 1 to K+ picrate ratio, the octamer (dG 1)8-K+ predominates in solution. The (dG 1)8-K+ supramolecular complex, formed by coordination of a single K+ ion by eight dG 1 monomers, is robust and structurally unique. The 1H NMR chemical shifts for both the exchangeable and nonexchangeable protons of (dG 1)8-KI in CDCl3 were assigned from a combination of 2D 1H-1H and 13C-1H correlation experiments. One set of 1H NMR signals corresponds to a dG 1 nucleoside with an anti conformation about the C(1')-N(9) glycosidic bond, whereas the other set of signals is due to 50% of the didecanoyl dG 1 adopting a syn conformation. Although the possible arrangements of an octamer containing a 1:1 ratio of anti dG 1 to syn dG 1 are many, the present NMR analysis leads to a defined single species composed of two G-quartets. In one tetramer, all of the dG 1 components have a syn conformation about the C(1')-N(9) glycosidic bond, while the other tetramer has an "all-anti" conformation. Moreover, intertetramer NOEs are consistent with stacking of the "all-anti" tetramer in a "head-to-tail" orientation on top of the "all-syn" tetramer, thus sandwiching a central K+ ion. This solution structure is, to our knowledge, different from all of the assembled structures described so far for guanine aggregates. Presumably, the K+-bound octamer represents the first observable stage of the assembly process in the aggregation of dG 1.