β-Trioxopyrrocorphins: pyrrocorphins of graded aromaticity

Octaethyltrioxopyrrocorphins unexpectedly show macrocycle-aromatic properties, even though they contain the macrocyclic π-system of the non-aromatic pyrrocorphins (hexahydroporphyrins). Two of the four possible triketone regioisomers were first reported in 1969 by one-pot oxidation of octaethylporphyrin but remained essentially unexplored since. We detail here the targeted preparation of the remaining two triketone isomers and the optical and NMR spectroscopic properties of all isomers. All four regioisomers possess unique electronic properties, including broadly varying degrees of diatropicity that were experimentally determined using 1H NMR spectroscopy and computationally verified. Structural patterns modulating the aromaticity were recognized. These differences highlight the regioisomerically differentiated influences of the three β-oxo-functionalities. We also present the solid state structure of the two most common isomers (in their free base form or as zinc complexes), allowing further conclusions to be made about the resonance structures present in these triketones. Remarkably, also, the halochromic properties of the triketones differ sharply from those of regular (hydro)porphyrins, providing further support for the proposed 16-membered, 18 π-electron aromatic ring-current. The work conceptually expands the understanding of tris-modified hydroporphyrinoid analogues and the factors that enable and control porphyrinoid aromaticity.


Reproduction of Spectra
Free Base Trioxopyrrocorphins

Halochromic Properties of Trioxopyrrocorphins
For linear graphs, the slope of the graph is taken as the Hill coefficient (η), reflecting the stoichiometry of the event causing the optical change tracked. The graphs returned for the acid titration (TFA in CH2Cl2) of the triketones studied here are decidedly non-linear, suggesting the presence of multiple binding events. Thus, it was not possible for us to calculate the Hill coefficient for these reactions. .
The non-linear graphs required a third-order polynominal for best fit (r 2 > 0.994).  Figure S39. UV-Vis (CH2Cl2, blue traces and CH2Cl2 + TBAOH, red traces) of the mono-oxo and dioxochlorins indicated. Sufficient TBAOH was added to a sample recorded in red to achieve maximum changes (saturation), with dilution errors < 2%. Figure S40. Photographs of the cuvettes containing the solutions indicated, before and after the addition of acid/base. Figure S41. Comparison of the computed UV-vis spectra for the neutral (solid trace) and bisprotonated (broken trace) triketones indicated. The spectra were not shifted to account for systematic errors. Figure S42. Comparison of the computed UV-vis spectra for the neutral (solid trace) and deprotonated at pyrrole (dotted trace), deprotonated at pyrroline (broken trace), and bis-deprotonated (dashed trace) triketones indicated. The spectra were not shifted to account for systematic errors.

X-Ray Crystallography
Data for 8-O 2,7,18 Zn·pyridine were collected on a Bruker Quest diffractometer with a fixed chi angle, a Mo Ka wavelength (λ = 0.71073 Å) sealed tube fine focus X-ray tube, single crystal curved graphite incident beam monochromator, and a Photon II area detector. Data for 8-O 2,7,18 and 8-O 2,7,12 Zn·pyridine were collected on a Bruker Quest diffractometer with kappa geometry, a Cu Ka wavelength (λ = 1.54178 Å) I-µ-S microsource X-ray tube, laterally graded multilayer (Goebel) mirror for monochromatization, and a Photon III C14 area detector. Both instruments were equipped with an Oxford Cryosystems low temperature device and examination and data collection were performed at 150 K. Data were collected, reflections were indexed and processed, and the files scaled and corrected for absorption using APEX3 3 and SADABS 4 . The space groups were assigned using XPREP within the SHELXTL suite of programs 5,6 and solved by direct methods using ShelXS 6 and refined by full matrix least squares against F 2 with all reflections using Shelxl2018 7 and the graphical interface
Several diethyl methylene moieties were refined as disordered. The units were restrained to have geometries similar as another well-defined diethyl methylene moiety, and U ij components of ADPs were restrained to be similar for atoms closer to each other than 2.0 Å. Subject to these conditions the occupancy ratios refined to 0.850(16) to 0.150(16) for the moiety of C13A, to 0.665(15) to 0.335(16) for that of C8B, and to 0.797(10) to 0.203 (10) for that of C13B.
Two small voids of around 68 Å 3 (2% of the cell volume) between molecules were occupied by disordered semi-liquid solvate molecules. No substantial electron density peaks were found in the solvent accessible voids (less than 0.55 electron per Å 3 ) and the residual electron density peaks are not arranged in an interpretable pattern. The cif and fcf files were thus corrected for using reverse Fourier transform methods using the SQUEEZE routine (P. van der Sluis & A.L.

Details to the X-Ray Crystal Structure of 8-O 2,7,12 Zn·pyridine
A solvate area is occupied by either methanol or water. The major methanol fraction is internally hydrogen bonded to form tetramers. The minor water fraction, consists of two times three water molecules, in part H-bonded to one of the keto oxygen atoms and among themselves. Methanol C-O bond distances were restrained to be similar in length.
Two water O atoms, O5B and O6B, were restrained to be at least 2.80(2) Å apart. Water H atom positions were initially refined while a damping factor was applied and O-H and H×××H distances were restrained to 0.84(2) and 1.36(2) Å, respectively. Some water H atom positions were further restrained based on hydrogen bonding considerations and an anti-bumping restraint was applied to avoid close H×××H contacts. In the final refinement cycles the damping factor was removed and water H atoms were constrained to ride on their carrying oxygen atom. U ij components of ADPs for disordered atoms closer to each other than 2.0 Å were restrained to be similar. Subject to these conditions the occupancy ratio refined to 0.781(6) to 0.219(6).

Computational Methods
The trioxopyrrocorphin isomers in the neutral, singly (mono-) and doubly (di-anionic) deprotonated, and doubly (di-cationic) protonated states were geometry optimized with the BHandHLYP approximate density functional 9 and a dev2-SVP basis set. 10 The absence of negative or imaginary frequencies in a harmonic vibrational analysis was used to confirm that each of the obtained structures resided in a local minimum on the potential energy surface.
Our primary objective for the computations was to provide insight into the regioisomericdependent aromatic nature of the trioxopyrrocorphins. We have found through calculations on related porphotrilactone structures, which will be published elsewhere, that the best agreement between theory and experiment for the magnetic criterion of aromaticity is obtained by performing geometry optimizations and nuclear magnetic resonance (NMR) computations with a density functional, like BHandHLYP, that contains 50% exact (Hartree-Fock) exchange. This conclusion is consistent with prior work 11 and motivated the choice over the level of theory for our studies.
NMR computations were performed on the four neutral trioxopyrrocorphin isomers at the BHandHLYP/def2-TZVP 9,10 level of theory. The difference in the average 1 H chemical shifts for the inner N-H and the outer meso-C-H protons (δΔ NH,meso ) was computed as a measure of the diatropic ring current that could be directly compared to experiment. At the chosen level of theory, the comparison was found to be excellent, reproducing experimental δΔ NH,meso values within 0.4 ppm. To build on this result, the Iso-chemical shielding surface approach (ICSS) 12 implemented in MultiWFN 13 was employed to visualize the spatial distribution of the ZZ component of the magnetic shielding tensor 1.0 Å above the macrocyclic plane. In the ICSS method, which is a three-dimensional generalization of the nucleus independent chemical shift (NICS) technique, 14 a cube of evenly spaced probe or phantom atoms is placed around the molecule of interest, and the magnetic shielding at these points is computed. A cube of 132,440 probe atoms was constructed using the default settings for a "medium" quality grid in MultiWFN for each trioxopyrrocorphin.
The NICS(0) and NICS(1) values are based on the isotropic magnetic shielding value and the NICS metrics follow the same trend as the difference in NH-meso chemical shifts (Table S4) Note: the molecules in the calculation were oriented in the yz plane, so we are reporting the xx component of the magnetic shielding tensor. We are using the "zz" label because the result is invariant to rotation, and either way, we are providing the tensor component perpendicular to the macrocyclic plane.
The UV-vis absorption spectra for each trioxopyrrocorphin in the neutral, singly or doubly deprotonated, and singly protonated states were computed with the hybrid PBE0 density functional 15 and a 6-31+G(d) basis set. 16 We have shown previously that this level of theory well reproduces the optical spectra of porphyrinoids bearing β-oxo functionalities.