Joshua Akhigbe

Helimeric Porphyrinoids: Stereostructure and Chiral Resolution of meso-Tetraarylmorpholinochlorins

The synthesis and chiral resolution of free-base and Ni(II) complexes of a number of derivatives of meso-tetraphenylmorpholinochlorins, with and without direct β-carbon-to-o-phenyl linkages to the flanking phenyl groups, is described. The morpholinochlorins, a class of stable chlorin analogues, were synthesized in two to three steps from meso-tetraphenylporphyrin. The conformations and the relative stereostructures of a variety of free-base and Ni(II) complexes of these morpholinochlorins were elucidated by X-ray diffractometry. Steric and stereoelectronic arguments explain the relative stereoarray of the morpholino-substituents, which differ in the free-base and Ni(II) complexes, and in the monoalkoxy, β-carbon-to-o-phenyl linked morpholinochlorins, and the dialkoxy derivatives. The Ni(II) complexes were all found to be severely ruffled whereas the free-base chromophores are more planar. As a result of the helimeric distortion of their porphyrinoid chromophores, the ruffled macrocycles possess a stable inherent element of chirality. Most significantly, resolution of the racemic mixtures was achieved, both by classical methods via diastereomers and by HPLC on a chiral phase. Full CD spectra were recorded and modeled using quantum-chemical computational methods, permitting, for the first time, an assignment of the absolute configurations of the chromophores. The report expands the range of known pyrrole-modified porphyrins. Beyond this, it introduces large chiral porphyrinoid π-systems that exist in the form of two enantiomeric, stereochemically stable helimers that can be resolved. This forms the basis for possible future applications, for example, in molecular-recognition systems or in materials with chiroptic properties.

meso-Arylporpholactones and their Reduction Products

The rational syntheses of meso-tetraaryl-3-oxo-2-oxaporphyrins 5, known as porpholactones, via MnO(4)(-)-mediated oxidations of the corresponding meso-tetraaryl-2,3-dihydroxychlorins (7) is detailed. Since chlorin 7 is prepared from the parent porphyrin 1, this amounts to a 2-step replacement of a pyrrole moiety in 1 by an oxazolone moiety. The stepwise reduction of the porpholactone 5 results in the formation of chlorin analogues, meso-tetraaryl-3-hydroxy-2-oxachlorin (11) and meso-tetraaryl-2-oxachlorins (12). The reactivity of 11 with respect to nucleophilic substitution by O-, N-, and S-nucleophiles is described. The profound photophysical consequences of the formal replacement of a pyrrole with an oxazolone (porphyrin-like chromophore) or (substituted) oxazole moiety (chlorin-like chromophore with, for the parent oxazolochlorin 12, red-shifted Q(x) band with enhanced oscillator strengths) are detailed and rationalized on the basis of SAC-CI and MNDO-PSDCI molecular orbital theory calculations. The single crystal X-ray structures of the porpholactones point at a minor steric interaction between the carbonyl oxygen and the flanking phenyl group. The essentially planar structures of all chromophores in all oxidation states prove that the observed optical properties originate from the intrinsic electronic properties of the chromophores and are not subject to conformational modulation.

Enhanced electrochemical oxygen reduction-based glucose sensing using glucose oxidase on nanodendritic poly[meso-tetrakis(2-thienyl)porphyrinato]cobalt(II)-SWNTs composite electrodes

The direct electrochemistry of glucose oxidase immobilized on a nanodendritic poly[meso-tetrakis(2-thienyl)porphyrinato]cobalt(II)-single walled carbon nanotube modified glassy carbon electrode (pCoTTP-SWNTs-Nafion-GOD/GCE) is reported. The immobilized GOD retained its activity and exhibited a surface controlled, reversible two-proton and two-electron transfer reaction with a fast heterogeneous electron transfer rate constant (ks) of 1.01 s(-1). The pCoTTP-SWNTs-Nafion matrix also showed an extremely low peak potential of -0.2 V vs. Ag/AgCl and strong response with respect to oxygen reduction. This forms the basis for the use of the pCoTTP-SWNTs-Nafion-GOD composite as a sensing platform for oxygen reduction-based glucose detection. The apparent Michaelis-Menten constant (Km,app) was estimated to be as low as 0.98 mM. A linear range up to 1mM glucose with a low detection limit of 5.33 μM (S/N=3) and a high sensitivity of 16.57 μA mM(-1) cm(-2) was achieved. The biosensor also shows excellent selectivity against 0.2 mM uric acid and ascorbic acid. These results indicate that the pCoTTP-SWNTs-Nafion-GOD/GCE has potential application in sensitive and selective glucose detection.

Oxazolochlorins. 2. Intramolecular cannizzaro reaction of meso-tetraphenylsecochlorin bisaldehyde.

Using mildly basic reaction conditions, the periodate-induced diol cleavage of meso-tetraphenyl-2,3-diolchlorin allows for the generation and isolation of the corresponding hitherto elusive free base secochlorin bisaldehyde. An intramolecular Cannizzaro reaction of this porphyrinoid generates three pyrrole-modified, oxazole-based porphyrins: the known porpholactol (2-oxa-3-hydroxychlorin) as the major product, known porpholactone (2-oxa-3-oxoporphyrin), and a novel porpholactol dimer that is linked through an acetal functionality. The structure of the dimer was confirmed by (1)H NMR spectroscopy, X-ray diffractometry, and ESI(+) collision-induced fragmentation mass spectrometry. The chromophores in the dimer are coupled electronically only to a minor extent. A mechanism to rationalize the formation of all products is advanced.

Quinoline-Annulated Porphyrins

Porphyrin-2,3-dione mono- and dioximes were used as starting materials for the efficient syntheses of mono- and bis-quinoline-annulated porphyrins and their corresponding N-oxides. Owing to an extended π-system, these novel porphyrinoid chromophores show significantly red-shifted UV-vis spectra compared to the parent porphyrins. A crystal structure exemplifies the nonplanar conformation of the macrocycle.

Mono- and Bisquinoline-Annulated Porphyrins from Porphyrin β,β'-Dione Oximes.

An acid-induced reaction of meso-tetraphenyl-2-hydroxyimino-3-oxoporphyrin leads, with concomitant loss of water, to a formal electrophilic aromatic substitution of the ortho-position of the phenyl group adjacent to the oxime, forming a quinoline moiety. Owing in part to the presence of a π-extended chromophore, the resulting meso-triphenylmonoquinoline-annulated porphyrin (λmax = 750 nm) possesses a much altered optical spectrum from that of the starting oxime (λmax = 667 nm). An oxidative DDQ-induced ring-closure process is also possible, generating the corresponding meso-triphenylmonoquinoline-annulated porphyrin quinoline N-oxide, possessing a slightly shifted and sharpened UV-vis spectrum (λmax = 737 nm). The connectivity of the chromophores was conclusively shown by NMR spectroscopy. Both ketone functionalities in meso-tetraphenyl-2,3-dioxoporphyrin can be converted, via the oxime and using the acid- or oxidant-induced reaction pathways, either in one step or in a stepwise fashion, to bisquinoline-annulated porphyrin (λmax = 775 nm) and its N-oxide (λmax = 779 nm), respectively. This process is complementary to a previously established pathway toward bisquinoline-annulated porphyrins. Their zinc(II), nickel(II), and palladium(II) complexes are also described. Several examples of the quinoline-annulated porphyrins were crystallographically characterized, proving their connectivity and showing their conformations that are extremely distorted from planarity. The work presents a full account on the synthesis, structure, and spectroscopic properties of these classes of NIR-absorbing dyes.

Porpholactams and chlorolactams: replacement of a β,β′-double bond in meso-tetraphenyl-porphyrin and -chlorin by a lactam moiety

Reaction of meso-tetraphenylporpholactone with hydrazine converts the lactone moiety to an N-aminolactam. It also reduces the opposite pyrrolic moiety of both the starting material and the N-aminolactam, generating chlorin-like chlorolactone and N-aminochlorolactam, respectively. Reductive N-N cleavage of the N-aminoporpholactam generates the parent porpholactam.

Effects of Strong Electronic Coupling in Chlorin and Bacteriochlorin Dyads

Achieving tunable, intense near-infrared absorption in molecular architectures with properties suitable for solar light harvesting and biomedical studies is of fundamental interest. Herein, we report the photophysical, redox, and molecular-orbital characteristics of nine hydroporphyrin dyads and associated benchmark monomers that have been designed and synthesized to attain enhanced light harvesting. Each dyad contains two identical hydroporphyrins (chlorin or bacteriochlorin) connected by a linker (ethynyl or butadiynyl) at the macrocycle β-pyrrole (3- or 13-) or meso (15-) positions. The strong electronic communication between constituent chromophores is indicated by the doubling of prominent absorption features, split redox waves, and paired linear combinations of frontier molecular orbitals. Relative to the benchmarks, the chlorin dyads in toluene show substantial bathochromic shifts of the long-wavelength absorption band (17-31 nm), modestly reduced singlet excited-state lifetimes (τS = 3.6-6.2 ns vs 8.8-12.3 ns), and increased fluorescence quantum yields (Φf = 0.37-0.57 vs 0.34-0.39). The bacteriochlorin dyads in toluene show significant bathochromic shifts (25-57 nm) and modestly reduced τS (1.6-3.4 ns vs 3.5-5.3 ns) and Φf (0.09-0.19 vs 0.17-0.21) values. The τS and Φf values for the bacteriochlorin dyads are reduced substantially (up to ∼20-fold) in benzonitrile. The quenching is due primarily to the increased S1 → S0 internal conversion that is likely induced by increased contribution of charge-resonance configurations to the S1 excited state in the polar medium. The fundamental insights gained into the physicochemical properties of the strongly coupled hydroporphyrin dyads may aid their utilization in solar-energy conversion and photomedicine.

Magnetic Circular Dichroism Spectroscopy of meso-Tetraphenylporphyrin-Derived Hydroporphyrins and Pyrrole-Modified Porphyrins

A large set of free-base and transition-metal 5,10,15,20-tetraphenyl-substituted chlorins, bacteriochlorins, and isobacteriochlorins and their pyrrole-modified analogues were investigated by combined UV-visible spectroscopy, magnetic circular dichroism (MCD), density functional theory (DFT), and time-dependent DFT (TDDFT) approaches and their spectral characteristics were compared to those of the parent compounds, free-base tetraphenylporphyrin 1H2 and chlorin 2H2. It was shown that the nature of the pyrroline substituents in the chlorin derivatives dictates their specific UV-vis and MCD spectroscopic signatures. In all hydroporphyrin-like cases, MCD spectroscopy suggests that the ΔHOMO is smaller than the ΔLUMO for the macrocycle-centered frontier molecular orbitals. DFT and TDDFT calculations were able to explain the large broadening of the UV-vis and MCD spectra of the chlorin diones and their derivatives compared to the other hydroporphyrins and hydroporphyrin analogues. This study contributes to the further understanding of the electronic effects of replacing a pyrrole in porphyrins by pyrrolines or other five-membered heterocycles (oxazoles and imidazoles).

Quinoline-annulated chlorins and chlorin-analogs

The OsO4-mediated dihydroxylation of quinoline-annulated porphyrin generates a quinoline-annulated dihydroxychlorin in a regioselective fashion. Its dihydroxypyrroline moiety, located at the opposite of the annulated pyrrole, is susceptible to the same functional group interconversions we previously demonstrated for non-annulated dihydroxychlorins: oxidations to the corresponding dione, lactone, and dialkoxymorpholine derivatives. The quinoline-annulated chlorin and derivatives are all characterized by absorption spectra that are much broadened and between 130 and 220 nm red-shifted compared to their non-annulated analogs. Absorbance maxima in the NIR up to well above 800 nm were recorded. We attribute the bathochromic shift to their extended π-systems and inferred non-planarity, highlighting that quinoline-annulation is a particularly effective and simple strategy to red-shift the absorption spectra of chlorins and chlorin analogs.