L-allo-Threoninol

We have synthesized acyclic allo-threoninol nucleic acids (allo-aTNAs), artificial xeno-nucleic acids (XNAs) that are diastereomers of acyclic threoninol nucleic acids (aTNAs), and have investigated their supramolecular properties. The allo-aTNAs formed homo-duplexes in an antiparallel manner but with lower thermal stability than DNA, whereas aTNAs formed extremely stable homo-duplexes. The allo-aTNAs formed duplexes with complementary aTNAs and serinol nucleic acid (SNA). The affinities of L-allo-aTNA were the highest for L-aTNA and the lowest for D-aTNA, with SNA being intermediate. The affinities of D-allo-aTNA were the reverse. Circular dichroism measurements revealed that L- and D-allo-aTNAs had weak right-handed and left-handed helicities, respectively. The weak helicity of allo-aTNAs likely explains the poor chiral discrimination of these XNAs, which is in contrast to aTNAs that have strong helical orthogonality. Energy-minimized structures of L-allo-aTNA/RNA and L-allo-aTNA/L-allo-aTNA indicated that the methyl group on the allo-aTNA strand is unfavourable for duplex formation. In contrast, the methyl group on L-aTNA likely stabilizes the duplex structure via hydrophobic effects and van der Waals interactions. Thus, the configuration of the methyl group on the XNA scaffold had an unexpectedly large impact on the hybridization ability and structure.

The rotational spectra of the amino alcohols d-allo-threoninol, 2-amino-1,3-propanediol, and 1,3-diamino-2-propanol and the triamine analog, propane-1,2,3-triamine, have been investigated under jet-cooled conditions over the 7.5-18.5 GHz frequency range using chirped-pulsed Fourier transform microwave spectroscopy. Microwave transitions due to three conformers of d-allothreoninol, four conformers of 2-amino-1,3-propanediol, four conformers of 1,3-diamino-2-propanol, and four conformers of propane-1,2,3-triamine have been identified and assigned, aided by comparison of the fitted experimental rotational constants with the predictions for candidate structures based on an exhaustive conformational search using force field, ab initio and DFT methods. Distinctions between conformers with similar rotational constants were made on the basis of the observed nuclear quadrupole splittings and relative line strengths, which reflect the direction of the permanent dipole moment of the conformers. With three adjacent H-bonding substituents along the alkyl chain involving a combination of OH and NH2 groups, hydrogen-bonded cycles (3 H-bonds) and chains (2 H-bonds) remain close in energy, no matter what the OH/NH2 composition. Two families of H-bonded chains are possible, with H-bonding substituents forming curved chain or extended chain structures. Percent populations of the observed conformers were extracted from the relative intensities of their microwave spectra, which compare favorably with relative energies calculated at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory. In glycerol (3 OH), d-allothreoninol (2 OH, 1 NH2), 2-amino-1,3-propanediol (2 OH, 1 NH2), and 1,3-diamino-2-propanol (1 OH, 2 NH2), H-bonded cycles are most highly populated, followed by curved chains (3 OH or 2 OH/1 NH2) or extended chains (1 OH/2 NH2). In propane-1,2,3-triamine (3 NH2), H-bonded cycles are pushed higher in energy than both curved and extended chains, which carry all the observed population. The NH2 group serves as a better H-bond acceptor than donor, as is evidenced by optimized structures in which H-bond lengths fall into the following order: r(OH···N) ≈ r(OH···O) < r(NH···N) ≈ r(NH···O).