Stereochemistry controlled by an asymmetric sulfur atom, and a rare example of a kryptoracemate.

The ligands 4-methylthio-6-phenyl-2,2'-bipyridine (1) and the corresponding sulfoxide (2) and sulfone (3) have been synthesized and characterized in solution, and in the solid state by single crystal X-ray diffraction. Compounds 2 and 3 crystallize in the same space group (C2/c) with similar unit cell parameters; a small increase in the unit cell volume allows for the presence of the extra oxygen atom in 3. The sulfoxide and sulfone groups adopt conformations that permit intramolecular O···HC(aryl) hydrogen bonds. The complexes [Ir(ppy)(2)L][PF(6)] with L = 1, 2 or 3 have been prepared and characterized. The asymmetric sulfur atom in ligand 2 gives rise to pairs of diastereoisomers of the complex which can be distinguished in the (1)H and (13)C NMR spectra. In solution, exchange of [PF(6)](-) by [Δ-TRISPHAT](-) gives rise to four diastereoisomers and we observed good dispersion of (1)H NMR resonances, especially for those assigned to protons close to the asymmetric sulfur atom. A single crystal X-ray diffraction study of 2{[Ir(ppy)(2)(3)][PF(6)]}·CHCl(3)·3H(2)O reveals that the complex crystallizes in the chiral space group P2(1)2(1)2(1), the asymmetric unit containing crystallographically independent Δ- and Λ-[Ir(ppy)(2)(3)](+) cations. This provides a rare example of a so-called kryptoracemate in the solid state. In MeCN solution, [Ir(ppy)(2)(1)][PF(6)], [Ir(ppy)(2)(2)][PF(6)] and [Ir(ppy)(2)(3)][PF(6)] are weakly emissive (λ(em) = 600, 647 and 672 nm, respectively) and preliminary studies of the electroluminescent properties of [Ir(ppy)(2)(2)][PF(6)] indicate that the complexes are not suitable candidates for LECs.

Discrimination against the cytosine analog tC by Escherichia coli DNA polymerase IV DinB.

The cytosine analog 1,3-diaza-2-oxophenothiazine (tC) is a fluorescent nucleotide that forms Watson-Crick base pairs with dG. The Klenow fragment of DNA polymerase I (an A-family polymerase) can efficiently bypass tC on the template strand and incorporate deoxyribose-triphosphate-tC into the growing primer terminus. Y-family DNA polymerases are known for their ability to accommodate bulky lesions and modified bases and to replicate beyond such nonstandard DNA structures in a process known as translesion synthesis. We probed the ability of the Escherichia coli Y-family DNA polymerase DinB (Pol IV) to copy DNA containing tC and to incorporate tC into a growing DNA strand. DinB selectively adds dGTP across from tC in template DNA but cannot extend beyond the newly formed G:tC base pair. However, we find that DinB incorporates the tC deoxyribonucleotide triphosphate opposite template G and extends from tC. Therefore, DinB displays asymmetry in terms of its ability to discriminate against the modification of the DNA template compared to the incoming nucleotide. In addition, our finding that DinB (a lesion-bypass DNA polymerase) specifically discriminates against tC in the template strand may suggest that DinB discriminates against template modifications in the major groove of DNA.

CG base pair recognition within DNA triple helices by modified N-methylpyrrolo-dC nucleosides.

3-Aminophenyl-modified analogues of the bicyclic nucleoside N-methyl-3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one were synthesised and incorporated directly into triplex-forming oligonucleotides in order to utilise their extended hydrogen bonding motif for recognition of the CG base pair. All analogues demonstrated strong binding affinity and very good selectivity for CG from pH 6.2 to 7.0; a marked improvement on previous modifications.

Supramolecular helical porphyrin arrays using DNA as a scaffold.

A diphenyl porphyrin substituted nucleotide was incorporated site specifically into DNA, leading to helical stacked porphyrin arrays in the major groove of the duplexes. The porphyrins show an electronic interaction which is significantly enhanced compared to the analogous tetraphenyl porphyrin (TPP) as shown in the large exciton coupling of the porphyrin B-band absorbance. Analogous to the TPP-DNA, an induced helical secondary structure is observed in the single strand porphyrin-DNA. The modified DNA can be hybridised to an immobilised complementary strand leading to fluorescent beads.

Porphyrin-DNA: a supramolecular scaffold for functional molecules on the nanometre scale.

We are pursuing the aim to use DNA as a supramolecular scaffold for the creation of electronically functional molecules on the nanometre scale. Here, we give a review on our results on porphyrin modified nucleotides used for this purpose. A general synthetic route to porphyrin-nucleotides has been devised, and the building blocks can be incorporated into oligonucleotides using standard solid phase synthesis methods. Up to 11 porphyrins were incorporated into DNA, reaching a length of approximately 4 nm in the array. The spectroscopic data are consistent with a porphyrin induced secondary structure stabilisation in the single strands.

DNA as supramolecular scaffold for porphyrin arrays on the nanometer scale.

Tetraphenyl porphyrin substituted deoxyuridine was used as a building block to create discrete multiporphyrin arrays via site specific incorporation into DNA. The successful covalent attachment of up to 11 tetraphenyl porphyrins in a row onto DNA shows that there is virtually no limitation in the amount of substituents, and the porphyrin arrays thus obtained reach the nanometer scale (approximately 10 nm). The porphyrin substituents are located in the major groove of the dsDNA and destabilize the duplex by deltaT(m) 5-7 degrees C per porphyrin modification. Force-field structure minimization shows that the porphyrins are either in-line with the groove in isolated modifications or aligned parallel to the nucleobases in adjacent modifications. The CD signals of the porphyrins are dominated by a negative peak arising from the intrinsic properties of the building block. In the single strands, the porphyrins induce stabilization of a secondary helical structure which is confined to the porphyrin modified part. This arrangement can be reproduced by force-field minimization and reveals an elongated helical arrangement compared to the double helix of the porphyrin-DNA. This secondary structure is disrupted above approximately 55 degrees C (T(p)) which is shown by various melting experiments. Both absorption and emission spectroscopy disclose electronic interactions between the porphyrin units upon stacking along the outer rim of the DNA leading to a broadening of the absorbance and a quenching of the emission. The single-stranded and double-stranded form show different spectroscopic properties due to the different arrangement of the porphyrins. Above T(p) the electronic properties (absorption and emission) of the porphyrins change compared to room temperature measurements due to the disruption of the porphyrin stacking at high temperature. The covalent attachment of porphyrins to DNA is therefore a suitable way of creating helical stacks of porphyrins on the nanometer scale.