The study of the anion recognition mechanisms, playing a crucial role in bio- and environmental chemistry, has been developed more slowly than the cation counterpart. Indeed, anions can have a wide variety of molecular geometries that increases the difficulty in designing a specific receptor. The anion coordination chemistry is mainly based on the non covalent stabilization due to N-H, C-H groups, and in a certain amount to the underexplored interactions such as anion-p and halogen bonding. Many efforts have been done to develop experimental and theoretical methodologies aimed to investigate the nature and the intensity of non covalent interactions involved in the stabilization of supramolecular assemblies. However, the knowledge of their intrinsic features needs a gas-phase experimental approach, in order to rule out any environmental effect. Intra- and intermolecular interactions fully develop in the gas phase, where the study of the conformational freedom and of the intrinsic binding properties is a challenging task. In the present project, a multi-dimensional mass spectrometric (MS) platform will be dedicated to the investigation of several potassium-containing complexes [Z·H·K·A]+ formed between a protonated in-house synthesized hexaazamacrocycle (Z) and the anion of organic and inorganic acid (HA): the kinetics of ligand exchange reaction (ESI-FT-ICR-MS) and the collisional cross section (ion-mobilty MS) of different [Z·H·K·A]+ adducts will be measured. The presence of four chirogenic centres in the Z structure will provide a further three-dimensional probe. Indeed, the meso-form and the RRRR- and SSSS-macrocycle could have a different folding induced by a different intra-molecular hydrogen bond network. All the experimental results will be supported by the a proper theoretical approach that will simulate the investigated complexes in both the gas and the condensed phase.
Over the last twenty years, our group devoted many efforts to the gas phase investigation of intra-and intermolecular interactions occurring in different systems that have been selected on the ground of their archetypal importance from the structural standpoint, or for their crucial importance in several biochemical processes as well as in the environmental chemistry. In this regard, anion coordination chemistry is a very quickly growing field that is supposed to be transversal to several branches of knowledge. The formation of supramolecular assemblies mediates the anion recognition, that can exploit even the host/guest chirality as a further three-dimensional probe to gain the highest quality information concerning the intimate nature of the non covalent interactions involved in the aggregate. The protonated form of the hexaazamacrocycle Z, as described in the previous section, exhibits an exceptional affinity towards the potassium cation; the so-formed [Z¿H¿K]2+ dication can coordinate a mono- or polyatomic anion as a contact ion pair, in the [ZH+·K+·A ¿] form, or in the classical [ZK+·AH] structure. The anion-selectivity of our system is actually based on the non covalent network stabilized by the N-H amino groups acting as hydrogen bond donors. Finally, the presence of the alkali cation can equip the aggregate with a further specific structural feature constraining the guest to a specific orientation. The protonated or deprotonated state of the anion in the aggregate can significantly affect the folding of the macrocycle, i.e. by inducing a ¿twisted¿ or an ¿open chair¿ arrangement. Since the ion mobility into a drift tube is inversely proportional to the CCS of the ion itself, that in turn depends on its shape, charge and size, the CCS measurement will allow to determine whether different regioisomers coexist. The same species will allow to react into the FT-ICR in a ligand displacement reaction, and the reaction mechanism can be pointed out by the correlation between the nature of the guest and the measured rate constant. The theoretical modeling will provide the most plausible structures in argeement with both the measured CCS and the proposed reaction coordinate.
A new perspective of this project consists also in providing the anion coordination chemistry with a molecular modeling capable to simulate the supramolecular aggregate in both the condensed and the gas phase. Indeed, the solvent evaporation occurring in the ESI source makes increase the ionic strength very fast, and higher energy structures from the ESI source can be kinetically trapped and transferred to the gas phase. Then fundamental questions arise from this intriguing topic: is there a coincidence between the stability order of the isomeric forms of any given ion in solution and in the gas phase? If not, is the structure of the native ion preserved in the gas phase?
The core of this proposal, aimed to answer the previous questions, is the study of anion recognition, that can provide a fundamental contribution to the comprehension of processes that cannot be fully understood in a study exclusively carried out in the condensed phase, where the environmental factors can affect or even overcome the development of the intrinsic forces involved.
The anion affinity can be understood by characterizing in the gas phase the coordination site(s) and then by comparing the emerged structural features with that resulting from simulations in condensed phase. The acquired knowledge of the factors affecting the anion coordination when a meso-macrocycle or chiral host/guest pairs are used, can be exploited to develop a reliable mass spectrometry analytical approach applied to the anion-sensing. Finally, the chirality effects on noncovalent interactions involved in the relative stabilization of diastereomeric supramolecular adducts will be analyzed in terms of their energy (theoretical approach), shape (IM-MS), and reactivity (FT-ICR experiments) implications.