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Designing viable Möbius Aromatic Systems using Computational Chemistry

Final Report Summary - CCMOBIUS (Designing viable Möbius Aromatic Systems using Computational Chemistry)

The EU funded research project CCMOBIUS was focused on the design of novel Möbius aromatic compounds from expanded porphyrins with applications as non-linear optical materials and molecular switches using computational chemistry methods. Although the concept of Möbius aromaticity was proposed on 1964, the synthesis of the first Möbius molecule was a challenge during forty years since the implementation of a smooth conjugated pi network and a twisted conformation in a single molecule is not easy. Only recently, expanded porphyrins were shown to have definite advantages in the formation of Möbius aromatic molecules such as (i) overall conformational flexibility, (ii) multiple oxidation states which can be easily interconverted by two-electron redox reactions, (iii) ability to invert, or “flip out”, the pyrrolic subunits and (iv) possibility of “locking in” Möbius conformations through metallation by the formation of both N-metal and C-metal bonds. Besides the Möbius topology, these large macrocycles adopt a variety of intriguing structures, such as planar or chiral figure-eight conformations, which can be interconverted under certain conditions (temperature, solvent, pH, etc).

The vast structural diversity and the extended pi-conjugation pathway exhibited by expanded porphyrins has led to diverse applications such as ion sensors, near-infrared dyes, two-photon absorption materials, and nonlinear optical materials. Interestingly, the photophysical properties are strongly dependent on the conformation and aromaticity/antiaromaticity of the π-electron system. Therefore, the control of the molecular topology is crucial for most applications. In order to find the optimum conditions for Möbius aromatic expanded porphyrin, we have carried out a quantum chemical study focusing on diverse aspects such as conformational analysis, dynamical switch between Hückel and Möbius structures, aromaticity and metal-ligand interactions. Furthermore, different conformational control methods have been explored in our research such as solvent, protonation and meso-substituents. In this period, the conformations and properties of penta-, hexa- and heptaphyrins has been investigated using mainly Density Functional Theory (DFT) methods. As the role of the aromaticity, strain and metallation in the stability of Möbius aromatic compounds is unclear in advance, we have evaluated them independently using different combination of macrocycles (small vs large porphyrin ring), substituents at the meso-positions and metals (group 10 vs. group 11 metals). First, we were focused on expanded porphyrins without metals with different macrocycle size and oxidation state, and then the metallation behaviour was investigated.

The conformational stability depends on various factors, such as the ring strain of the macrocycle, intra/intermolecular hydrogen bonding, steric effects of meso-substituents and aromaticity. We have proposed a set of descriptors to quantify independently the contribution of the different factors. Aromaticity has been quantified using energetic, magnetic, structural and reactivity criteria, whereas the steric effects of the substituents were analysed in terms of the non-covalent interaction index. For the first time, aromatic stabilization energies, magnetic susceptibility exaltation and relative hardness were computed for expanded porphyrins. From the correlation analysis, it was proven that magnetic descriptors together with the relative hardness are the best indices to quantify both Möbius and Hückel aromaticity. The torsional descriptors together with the aromaticity indices are shown to be very useful for identifying porphyrinoids with an optimum balance between the ring strain imposed by the twist and the energy stabilization due to aromaticity.

First of all, the viability of Möbius topologies in [26] and [28]hexaphyrins( was investigated since they are among the most studied macrocycles in the area of expanded porphyrins. A large amount of experimental information on their conformations is currently available, being certainly appropriate to test the novel computational approach. We found that the conformation of the hexaphyrin macrocycle is strongly dependent on the oxidation state. [26]hexaphyrin strongly prefers a Hückel conformation, planar and highly aromatic, whereas Hückel and Möbius conformers coexist in dynamic equilibrium for the [28]hexaphyrin. The conformational equilibrium of [28]hexaphyrin is quite sensitive to the solvent and, importantly, the twist induces a dramatic change in the magnetic properties and reactivity of the macrocycle. These features make [28]hexaphyrin suitable for the development of molecular switches with practical applications.

Secondly, the developed computational approach was applied to determine the conformational preferences and the topological interconversion pathways in neutral and protonated [32]heptaphyrins( In the neutral state, the antiaromatic figure-eight conformation is preferred over the aromatic Möbius topology due to its more effective hydrogen bonding, although a Hückel-Möbius aromaticity switch is feasible with a low activation barrier. The conformational equilibrium is solvent-dependent, so polar solvents further stabilize the Möbius strip structure. In addition, conformational control of neutral [32]heptaphyrins can be effectively achieved by meso-substituents and protonation. It is found that the two-photon absorption (TPA) cross-section value increases significantly in the triprotonated heptaphyrins due to the formation of aromatic Möbius species.

A similar approach was then applied to the family of pentaphyrins. Pentapyrrolic macrocycles are drug leads for photodynamic therapy. However, attempts to synthetize fully meso-substituted pentaphyrins resulted unexpectedly in the isolation of N-fused systems in two stable oxidation states. Interestingly, we found that removing only one substituent provides stable aromatic non-fused [22]pentaphyrin with a high TPA cross-section value. On the contrary, the N-fusion reaction is thermodynamically favoured in [24]pentaphyrins due to the release of strain, so they are expected to be quite unstable. A weakly aromatic N-fused [24]pentaphyrins with Möbius topology is provided by the trifluoromethyl substituent, although the large dihedral angles preclude effective delocalization in pentapyrrolic macrocycles. In short, Möbius topologies turns out to be indeed accessible for [4n] pi expanded porphyrins, although fully aromatic Möbius structures are only achievable by protonated [32]heptaphyrin and [28]hexaphyrin, among the investigated compounds. A close relationship between the molecular topology, the number of pi electrons, aromaticity and photophysical properties is found.

Regarding to the metal effect, we found that the group 10 metals (Ni2+, Pt2+, Pd2+) locked the Möbius conformation in the [28]hexaphyrin, whereas the group 11 metals (Cu3+, Ag3+, Au3+) provide antiaromatic Hückel-type complexes. On the other hand, the metal complexes of [26]hexaphyrin provides aromatic Hückel structures with novel metal-carbon bonds. The computational results reveal novel coordination abilities and a variety of metal complexes depending upon the oxidation state of the ligand and the metal ion. The computed metal affinities might be important for the development of practical sensors for the quantification of metal ions in environmental samples.

Our computational results are in excellent agreement with the experimental data available for penta-, hexa- and heptaphyrins and provide a fully description and comprehension of the Möbius aromaticity. It is shown that computational chemistry is a powerful tool in the design of Möbius aromatic expanded porphyrins and promising molecular switches and our theoretical results can be used as a guide for experimental groups in academic and industrial environments. In addition, the knowledge derived from this project could assist the design of novel porphyrin nanodevices for photovoltaic, photonic and biomedical applications.