Porphyrin Atropisomerism - a New Twist in Molecular Recognition and Supramolecular Architectures

Abstract

The unifying theme of the work reported in this thesis is the exploitation of the flexibility of the porphyrin macrocycle using sterically demanding units to construct supramolecular receptors for selective guest encapsulations. Special interest was directed toward porphyrin stereoisomers called atropisomers, their specific molecular arrangements in crystal lattices, and investigation of host-guest interactions. The concepts of nonplanarity, atropisomerism, and examples of modern porphyrin-based sensors are covered in the general introduction in Chapter 1. The overall objective and aims with brief overview of each result and discussion chapters is detailed in Chapter 2. Supramolecular engineering in Chapters 3 and 4 showcases the combination of porphyrin nonplanarity with a well-established molecular design principle for planar systems, the bulky “picket fence” architecture. Chapter 3 details a design evolution from ortho-positions of meso-phenyl residues in dodecasubstituted porphyrin systems to less hindered para- and meta-sites, developing selective demethylation based on steric interference. Isolation of the symmetrical target picket fence derivative 2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetrakis(3,5-dipivaloyloxy- phenyl)porphyrin was investigated under two synthetic pathways. The obtained insight was used to isolate unsymmetrical 2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetrakis(2-nitro-5-pivaloyloxyphenyl)porphyrin. Upon separation of the atropisomers, a detailed single-crystal X-ray crystallographic analysis was performed, showing a suite of intermolecular interactions. Steric crowding in Chapter 3 proved a hindrance to synthesis of specific target species. In Chapter 4, a strategy to introduce less bulky acetyl groups to all possible atropisomeric species of [5,10,15,20-tetrakis(2-aminophenyl)-2,3,7,8,12,13,17,18-octaethylporphyrinato]nickel(II) is reported. Nonplanarity, combined with the spatial instalment of ‘blocking’ groups from the picket fence, enables fine manipulation of the receptor site. The sophisticated assemblies from the X-ray crystal structure analysis show molecular arrangement driven by complementary non-covalent bonding interactions, which lead to encapsulation of small molecules in parallel channels or solvent-accessible voids, depending on the orientation of the peripheral groups. By engineering molecular strain, the introduction of the original ‘picket- fence’ units is allowed, locking in a particular conformation. The electronic effects of steric repulsions are reflected in spectrophotometric changes. This steric strain introduced by the peripheral units is used to enrich minor atropisomers. The extent to which the rotation of porphyrin atropisomers can be restricted or forbidden is explored in Chapter 5. A novel molecular design was chosen to include large molecular motifs (diphenylmethane) on ortho-positions of aryl rings, a 5,15- meso substitution pattern and non-functionalized β-positions to minimize complexity. The target compound, isolated in five steps, showed the expected two stereo-conformations; these atropisomers did not re-equilibrate under solvothermal conditions. Upon bromination the drastic change in solubility of the isomers allowed recrystallization to be used in separating rotamers. X-ray crystallographic studies showed packing dominated by – interactions and the first example of atropisomeric porphyrin co-crystallization. In Chapter 6, as a first step towards isolated porphyrin ‘enzyme-like’ active centers, structural and spectroscopic study of hostguest interactions are detailed. Substrate binding to the inner core porphyrin system shows that a highly saddle-distorted porphyrin with peripheral amino binding groups in α4-[2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetrakis(2-aminophenyl)porphyrin] encapsulates analytes in a switchable manner dependent on the acidity of the solution. The supramolecular ensemble exhibits exceptionally high affinity for the pyrophosphate anion and does so in preference to other anions. 1H NMR spectroscopic studies provided insight into the likely mode of binding action. Additionally, thorough X-ray structural analysis was used to investigate aspects of the weak host–guest interactions, that shows selective H-bonding complexation based on the accessibility to the inner core system. In Chapter 7, a fundamental issue of porphyrinoid stereochemistry, how to completely assign porphyrin atropisomers by NMR, is addressed. Using benzenesulfonic acid as an H-bonding partner to restrict movement, and performing 1D and 2D NMR spectroscopic analyses of through-bond and through-space coupling, allowed the characterization of all four rotamers of the nonplanar 2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetrakis(2-aminophenyl)porphyrin. From a method development perspective, charge-assisted complexation and the symmetry profile of the unique porphyrin atropisomers were found to offer a handle to accurately identify the rotamers using NMR techniques only. The inner core N–H signals alone were found to “fingerprint” each atropisomer. Chapter 8 explores porphyrin-based supramolecular receptors’ activity in a chiral environment, combining each of the atropisomers of 2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetrakis(2-aminophenyl)porphyrin with (S and R) camphorsulfonic acid. Based on NMR analyses of the atropisomeric receptors, host symmetry is shown to be affected by nonplanar induction, and further desymmetrized in the presence of a chiral guest. The exposed porphyrin inner core (N–H), with its strong hydrogen bond abilities and appearance in previously underutilized region of the spectrum (below 0 ppm.), has been exploited in enantiomeric excess (e.e.) analysis, outperforming current state-of-the-art prochiral solvating agents (pro-CSA). The findings are complemented by extensive 2D NMR studies, including the first reporting of e.e. dependent signal splitting in non-hydrogen NMR, and supporting UV-vis absorption spectroscopic measurements.