Stepwise Nucleation of Aniline: Emergence of Spectroscopic Fingerprints of the Liquid Phase.

This work deals with the controlled nucleation of aniline from the isolated molecule until formation of a moderately large aggregate: aniline nonamer. The structure of the cluster at each step of the nucleation was unravelled combining mass-resolved IR spectroscopy and computational chemistry, demonstrating that aggregation is primarily guided by formation of extensive N-H⋅⋅⋅N hydrogen-bond networks that give the aggregates a sort of branched backbone, in clear competition with multiple N-H/C-H⋅⋅⋅π and π⋅⋅⋅π interactions. The result is the co-existence of close nucleation paths connecting relational aggregates. The delicate balance of molecular forces makes the aniline clusters a challenge for molecular orbital calculations and an ideal system to refine the present nucleation models. Noticeably, spectroscopic signatures characteristic of the condensed phase are apparent in the nanometer-size aggregates formed in this work.

Competition between stacked and hydrogen bonded structures of cytosine aggregates.

The four bases of DNA constitute what is known as the "alphabet of life". Their combination of proton-donor and acceptor groups and aromatic rings allows them to form stacking structures and at the same time establish hydrogen bonds with their counterparts, resulting in the formation of the well-known double-helix structure of DNA. Here we explore the aggregation preferences of cytosine in supersonic expansions, using a combination of laser spectroscopic techniques and computations. The data obtained from the experiments carried out in the cold and isolated environment of the expansion allowed us to establish which are the leading interactions behind aggregation of cytosine molecules. The results obtained demonstrated that ribbon-like structures held together by hydrogen bonds are the preferred conformations in the small clusters, but once the tetramer was reached, the stacking structures became enthalpically more stable. Stacking is further favoured when cytosine is replaced by its 1'-methylated version, as demonstrated by quantum-mechanical calculations performed using the same level that reproduced the experimental results obtained for cytosine aggregates. A discussion on the biological implications that such observations may have is also offered.

Influence of the Anomeric Conformation in the Intermolecular Interactions of Glucose.

Carbohydrates are, together with amino acids, DNA bases, and lipids, the building blocks of living beings. They play a central role in basic functions such as immunity and signaling, which are governed by noncovalent interactions between sugar units and other biomolecules. To get insights into such interactions between monosaccharide units, we used a combination of mass-resolved laser spectroscopy in supersonic expansions and molecular structure calculations. The results obtained clearly demonstrate that the small stability difference between the α/ß anomers of glucopyranose derivatives is reversed and amplified during molecular aggregation, making the complexes of the ß-anomers significantly more stable. The amplification mechanism seems to be formation of extensive hydrogen-bond networks extending through the two interacting molecules. The same mechanism must be at play in the interactions of biological and synthetic receptors with glycans, which exhibit, in general, a higher affinity for a specific anomer, usually the beta anomer.

Modeling the tyrosine-sugar interactions in supersonic expansions: glucopyranose-phenol clusters.

Sugars are fundamental building blocks for living organisms and their interaction with proteins plays a central role in fundamental biological processes, such as energy storage and production, post-transductional modifications or immune response. Understanding those processes require deep knowledge of the forces that drive the interactions at the molecular level. Here we explore the interactions between α/ß-methyl-d-glucopyranose and ß-phenyl-d-glucopyranose with phenol, and the chromophore of tyrosine, using a combination of mass-resolved laser electronic spectroscopy in supersonic expansions and quantum mechanical calculations. The structures of the complexes detected in the jet are stabilized by a subtle equilibrium between several types of weak interactions, among which the dispersion forces may tilt the balance. In particular, the small structural changes introduced by the orientation of the anomeric substituent are amplified by the interaction with phenol. Consequently, the number of conformational isomers detected experimentally is different for each system and they present also differences in the preferred solvation site. Furthermore, inclusion of entropic terms for the calculated structures is advisable to understand the energetic reasons for the detection of a small set of experimental conformational isomers.