A new pH sensitive fluorescent and white light emissive material through controlled intermolecular charge transfer.

A new, pH dependent and water-soluble, conjugated oligomer (amino, trimethylammonium oligophenylene vinylene, ATAOPV) was synthesized with a quaternary ammonium salt and an aromatic amine at the two ends of a π-conjugated oligomer, thus creating a strong dipole across the molecule. A unique white light LED is successfully fabricated from a stimuli responsive organic molecule whose emission properties are dominated by the pH value of the solution through controlled intermolecular charge transfer.

Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded conformations and show directional differences in stacking pattern.

The structural preorganization of isosequential ssDNA and ssRNA hexamers d/r(GAAAAC)(1) [J. Am. Chem. Soc. 2003, 125, 9948] have been investigated by NMR and molecular dynamics simulations. Analysis of the nuclear Overhauser effect spectrometry (NOESY) footprints in the aqueous solution has shown that there is a substantial population of ordered right-handed helical structure in both hexameric single-stranded DNA and RNA, which are reminiscent of their respective right-handed helical duplex form, despite the fact these single-stranded molecules are devoid of any intermolecular hydrogen bonds. The NMR-constrained molecular dynamics (1.5 ns) derived geometries of the adenine-adenine overlaps at each dinucleotide step of the hexameric ssDNA (1a) and ssRNA (1b) show that the relatively electron-rich imidazole stacks above the electron-deficient pyrimidine in 5' to 3' direction in ssDNA (1a) while, in contradistinction, the pyrimidine stacks above the imidazole in the 5' to 3' direction in ssRNA (1b). This also means that the pi-frame of the 5'-pyrimidine can interact with the relatively positively charged imino and amino protons in the 3' direction in ssRNA and in the 5' direction in ssDNA, thereby stabilizing the twist and slide observed in the stacked oligonucleotides. The differently preferred stacking geometries in ssDNA and ssRNA have direct physicochemical implications for self-assembly and pK(a) modulation by the nearest-neighbor interactions, as well as for the dangling-end stabilization effects and imino-proton reactivity.

Measurement of nucleobase pKa values in model mononucleotides shows RNA-RNA duplexes to be more stable than DNA-DNA duplexes.

To understand why the RNA-RNA duplexes in general has a higher thermodynamic stability over the corresponding DNA-DNA duplexes, we have measured the pK(a) values of both nucleoside 3',5'-bis-ethyl phosphates [Etp(d/rN)pEt] and nucleoside 3'-ethyl phosphates [(d/rN)pEt] (N = A, G, C, or T/U), modeling as donors and acceptors of base pairs in duplexes. While the 3',5'-bis-phosphates, Etp(d/rN)pEt, mimic the internucleotidic monomeric units of DNA and RNA, in which the stacking contribution is completely absent, the 3'-ethyl phosphates, (d/rN)pEt, mimic the nucleotide at the 5'-end. The pK(a) values of the nucleobase in each of these model nucleoside phosphates have been determined with low pK(a) error (sigma = +/-0.01 to 0.02) by (1)H NMR (at 500 MHz) with 20-33 different pH measurements for each compound. This study has led us to show the following: (1) All monomeric DNA nucleobases are more basic than the corresponding RNA nucleobases in their respective Etp(d/rN)pEt and (d/rN)pEt. (2) The pK(a) values of the monomeric nucleotide blocks as well as Delta pK(a) values between the donor and acceptor can be used to understand the relative base-pairing strength in the oligomeric duplexes in the RNA and DNA series. (3) The Delta G*(pKa) of the donor and acceptor of the base pair in duplexes enables a qualitative dissection of the relative strength of the base-pairing and stacking in the RNA-RNA over the DNA-DNA duplexes. (4) It is also found that the relative contribution of base-pairing strength and nucleobase stacking in RNA-RNA over DNA-DNA is mutually compensating as the % A-T/U content increases or decreases. This interdependency of stacking and hydrogen bonding can be potentially important in the molecular design of the base-pair mimics to expand the alphabet of the genetic code.

Cross-modulation of the pKa of nucleobases in a single-stranded hexameric-RNA due to tandem electrostatic nearest-neighbor interactions.

The pH titration studies (pH 6.7-12.1) in a series of dimeric, trimeric, tetrameric, pentameric, and hexameric oligo-RNA molecules [GpA (2a), GpC (3a), GpApC (5), GpA(1)pA(2)pC (6), GpA(1)pA(2)pA(3)pC (7), GpA(1)pA(2)pA(3)pA(4)pC (8)] have shown that the pK(a) of N(1)-H of 9-guaninyl could be measured not only from its own deltaH8G, but also from the aromatic marker protons of other constituent nucleobases. The relative chemical shift differences [Deltadelta((N)(-)(D))] between the protons in various nucleotide residues in the oligo-RNAs at the neutral (N) and deprotonated (D) states of the guanine moiety show that the generation of the 5'-(9-guanylate ion) in oligo-RNAs 2-8 reduces the stability of the stacked helical RNA conformation owing to the destabilizing anion(G(-))-pi/dipole(Im(delta)(-)) interaction. This destabilizing effect in the deprotonated RNA is, however, opposed by the electrostatically attractive atom-pisigma (major) as well as the anion(G(-))-pi/dipole(Py(delta)(+)) (minor) interactions. Our studies have demonstrated that the electrostatically repulsive anion(G(-))-pi/dipole(Im(delta)(-)) interaction propagates from the first to the third nucleobase quite strongly in the oligo-RNAs 6-8, causing destacking of the helix, and then its effect is gradually reduced, although it is clearly NMR detectable along the RNA chain. Thus, such specific generation of a charge at a single nucleobase moiety allows us to explore the relative strength of stacking within a single-stranded helix. The pK(a) of 5'-Gp residue from its own deltaH8G in the hexameric RNA 8 is found to be 9.76 +/- 0.01; it, however, varies from 9.65 +/- 0.01 to 10.5 +/- 0.07 along the RNA chain as measured from the other marker protons (H2, H8, H5, and H6) of 9-adeninyl and 1-cytosinyl residues. This nucleobase-dependent modulation of pK(a)s (DeltapK(a) +/- 0.9) of 9-guaninyl obtained from other nucleobases in the hexameric RNA 8 represents a difference of ca. 5.1 kJ mol(-)(1), which has been attributed to the variable strength of electrostatic interactions between the electron densities of the involved atoms in the offset stacked nucleobases as well as with that of the phosphates. The chemical implication of this variable pK(a) for guanin-9-yl deprotonation as obtained from all other marker protons of each nucleotide residue within a ssRNA molecule is that it enables us to experimentally understand the variation of the electronic microenvironment around each constituent nucleobase along the RNA chain in a stepwise manner with very high accuracy without having to make any assumption. This means that the pseudoaromaticity of neighboring 9-adeninyl and next-neighbor nucleobases within a polyanionic sugar-phosphate backbone of a ssRNA can vary from one case to another due to cross-modulation of an electronically coupled pi system by a neighboring nucleobase. This modulation may depend on the sequence context, spatial proximity of the negatively charged phosphates, as well as whether the offset stacking is ON or OFF. The net outcome of this electrostatic interaction between the neighbors is creation of new sequence-dependent hybrid nucleobases in an oligo- or polynucleotide whose properties are unlike the monomeric counterpart, which may have considerable biological implications.