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The constitution, configuration, and flexibility of the core sugars of DNA molecules alter their function in diverse roles. Conformational itineraries of the ribofuranosides (fs) have long been known to finely determine rates of processing, yet we also know that, strikingly, semifunctional DNAs containing pyranosides (ps) or other configurations can be created, suggesting sufficient but incompletely understood plasticity. The multiple conformers involved in such processes are necessarily influenced by context and environment: solvent, hosts, ligands. Notably, however, to date the unbiased, “naked” conformers have not been experimentally determined. Here, the inherent conformational biases of DNA scaffold deoxyribosides in unsolvated and solvated forms have now been defined using gas-phase microwave and solution-phase NMR spectroscopies coupled with computational analyses and exploitation of critical differences between natural-abundance isotopologues. Serial determination of precise, individual spectra for conformers of these 25 isotopologues in alpha (α-d) and beta (β-d); pyrano (p) and furano (f) methyl 2-deoxy-d-ribosides gave not only unprecedented atomic-level resolution structures of associated conformers but also their quantitative populations. Together these experiments revealed that typical 2E and 3E conformations of the sugar found in complex DNA structures are not inherently populated. Moreover, while both OH-5′ and OH-3′ are constrained by intramolecular hydrogen bonding in the unnatural αf scaffold, OH-3′ is “born free” in the “naked” lowest lying energy conformer of natural βf. Consequently, upon solvation, unnatural αf is strikingly less perturbable (retaining 2T1 conformation in vacuo and water) than natural βf. Unnatural αp and βp ribosides also display low conformational perturbability. These first experimental data on inherent, unbiased conformers therefore suggest that it is the background of conformational flexibility of βf that may have led to its emergence out of multiple possibilities as the sugar scaffold for “life’s code” and suggest a mechanism by which the resulting freedom of OH-3′ (and hence accessibility as a nucleophile) in βf may drive preferential processing and complex structure formation, such as replicative propagation of DNA from 5′-to-3′., The preferred conformations and populations of DNA ribopyranosides and furanosides were determined with atomic resolution in the gas phase and in water solution.

The rotational spectra of the parent species and of four water isotopologues (-DOH, -HOD, -DOD, and -H(18)OH) of the adduct 3-fluoropyridine-water have been investigated using pulsed supersonic-jet Fourier-transform microwave spectroscopy. From the rotational constants, the structure of the adduct was deduced where the water is linked to the aromatic ring through an intermolecular O-H···N hydrogen bond with a bond distance of 1.9961(5) Å and an O-H···N angle of 156.8(1)°. The shape of the complex is such that the water oxygen is in the plane of the aromatic ring, on the opposite side of fluorine, and forming a C-H···N weak hydrogen bond with the adjacent aromatic hydrogen.

The conformational landscapes of β-ionone and two mutants (α-ionone and β-damascone) have been analyzed by means of state-of-the-art rotational spectroscopy and quantum-chemical calculations. The experiments performed at high resolution and sensitivity have provided a deep insight into their conformational spaces, assigning more than 8000 transitions corresponding to the rotational structures of 54 different species (3 isomers, 14 conformers, and 40 isotopologues). Methyl internal rotation dynamics were also observed and analyzed. The work proved the great flexibility of β-ionone due to its flatter potential energy surface. This feature confers on β-ionone a wider ability to interconvert between conformers with rather similar energies with respect to its mutants, allowing the retinal ligand to better adapt inside the binding pocket.

The pure rotational spectrum of 1,2-dimethoxyethane was measured in the 6–18 and 59.6–74.4 GHz frequency ranges using a cavity-based pulsed jet Fourier transform microwave spectrometer and a Stark modulated free-jet millimeter-wave absorption spectrometer, respectively. Two conformers, TGT and TGG′, have been identified, together with their mono-substituted 13C isotopologues. Each rotational transition is split into several components due to the two methyl groups internal rotations. The corresponding V3 barriers have been experimentally determined. MP2/6-311++G(d,p) calculations have provided the determination of the conformational stabilities, structures and spectroscopic parameters.

The rotational spectrum of the weakly bound complex pentafluoropyridine·water has been investigated with pulsed jet Fourier transform microwave spectroscopy. From the analysis of the rotational parameters of the parent species and of three water isotopologues, the structural arrangement of the adduct has been unambiguously established. The results show that the full ring fluorination of pyridine has a dramatic effect on its binding properties: It inverts the electron density distribution above the ring, creating a π-hole, with respect to the typical π-cloud of benzene and pyridine. In the complex the water moiety lies above the aromatic ring with the oxygen lone pairs pointing toward its center. This lone pair···π-hole interaction stabilizes the adduct, and it is more stable than the in-plane O–H···N hydrogen bond normally found in the complexes involving nitrogen heterocyclic aromatic rings. Evidence of a large amplitude motion involving the weakly bound water molecule has also been observed and discussed.