Daniel J. Nurco

Novel routes to substituted 5,10,15-triarylcorroles

A one-pot procedure that allows the preparation of 5,10,15-triarylcorroles directly from the condensation of pyrrole and benzaldehydes, avoiding the concomitant formation of the corresponding tetraarylporphyrins, has been developed. This approach is general and allows the preparation of sterically hindered corroles from 2,6-disubstituted benzaldehydes, where the Rothemund approach failed. The first examples of fully substituted corrole free bases were prepared following this approach, but in this case corroles were obtained as a mixture with the corresponding dodecasubstituted porphyrins. Unsymmetrically substituted ABC corroles were obtained from the condensation of two different dipyrromethanes. A [2+12] biladiene-like approach afforded 10-(4-methylphenyl)-5,15-diphenylcorrole, along with a significant amount of tetraphenylporphyrin from the self-tetramerization of the starting pyrryl carbinol. An X-ray structure of 5,10,15-triphenylcorrole shows deviations from planarity that are attributed to the ster...

Synthesis, toxicity and biodistribution of two 5,15-di[3,5-(nido-carboranylmethyl)phenyl]porphyrins in EMT-6 tumor bearing mice

The total synthesis of a 5,15-di[3,5-(o-carboranylmethyl)phenyl]porphyrin 5, its zinc(II) complex 6, and the corresponding nido-carboranylporphyrins 7 and 8 are reported. The molecular structures of porphyrin 6 and of potassium nido-carborane were obtained and are described. The biodistribution of nido-carboranylporphyrins 7 and 8 in BALB/c mice bearing EMT-6 mammary tumors are presented and compared. Both compounds are effective tumor localizers and delivered therapeutic concentrations of boron to tumors (mean+/-standard deviation): 32.5+/-7.1 and 54.3+/-14 microg/g for 7 and 8, respectively, 2 days after the last of 3 injections of a total boron dose of 23 mg/kg body weight. The zinc(II) complex 8 was found to deliver 1.2-1.7 times higher amounts of boron to tumors than 7, with lower tumor-to-blood boron concentration ratios (9.8/1 and 4.7/1 for 7 and 8, respectively, 2 days after injections). The tumor-to-brain boron concentration ratios were >100/1 for both porphyrins 2 days after administration. Both nido-carboranylporphyrins 7 and 8 were well-tolerated at the concentrations used (75 and 78 mg/kg body weight, respectively) and no morbidity or mortality were observed in these studies.

5,10,15-Triphenylcorrole: a product from a modified Rothemund reaction

One-pot synthesis of 5,10,15-triphenylcorrole has been achieved by reaction of benzaldehyde with an excess of pyrrole; the triphenylphosphinocobalt complex of 5,10,15-triphenylcorrole has been structurally characterized using X-ray crystallography.

Investigations on the directive effects of a single meso-substituent via nitration of 5,12,13,17,18-pentasubstituted porphyrins: syntheses of conjugated β-nitroporphyrins

Abstract Vilsmeier formylation of 5-substituted 1,9-diunsubstituted dipyrromethanes afforded 1,9-diformyldipyrromethanes in good yields. Their MacDonald condensation with tetra-β-alkyldipyrromethanes produced 5,12,13,17,18-pentasubstituted porphyrins. A meso-electron-donating group, presumably acting by destabilizing the porphyrin a2u ground state, directs the nitrations to the meso-carbons. β-Nitration takes place on porphyrins bearing a meso-electron-withdrawing group. Unhindered β-nitro groups are shown to exert stronger electronic effects relative to meso-nitro groups by conjugating effectively with the porphyrin macrocycle.

β,β′-Fused metallocenoporphyrinsElectronic supplementary information (ESI) available: molecular structure of 10. See http://www.rsc.org/suppdata/cc/b1/b107732e/

The syntheses of a β,β′-fused ruthenocenoporphyrin (9) and a ferrocenoporphyrin dimer (11) are described.

Novel aspects of the chemistry of 1,19-diunsubstituted a,c- biladienes

Cyclization of a,c-biladienes in alcoholic solution gives corroles. When the same reaction is carried out in CHCl3 a completely different outcome is observed, and the product of the reaction is the corresponding open-chain biliverdin. The critical step for the cyclization to corrole is the formation of the fully conjugated 22,24-dihydro-a,b,c-bilatriene cation, which is allowed in methanol and appears to be prevented in CHCl3. The presence of substituents at the 10-position of the a,c-biladiene is also critical for the reaction; while a phenyl group strongly enhances the formation of corrole, in the case of alkyl groups the formation of both corrole and biliverdin is prevented. This result can reasonably be attributed to the failure to give a fully conjugated 22,24-dihydro-a,b,c-bilatriene structure for 10-alkyl substituted a,c-biladienes. Carrying out the a,c-biladiene cyclization in acidic methanol permits a new one-pot preparation of β-alkylcorroles.

First structural characterization of a covalently bonded porphyrin–carborane system

The first definitive crystal structure of a covalently bonded carborane–porphyrin system is reported; unusual inter- and intra-molecular carborane–porphyrin interactions are observed in the molecular structure and in variable temperature 1H NMR experiments.

Application of Matrix-Assisted Laser Desorption/Ionization Fourier Transform Mass Spectrometry to the Analysis of Planar Porphyrins and Highly Substituted Nonplanar Porphyrins

The applicability of matrix-assisted laser desorption/ionization (MALDI) Fourier transform mass spectrometry to the analysis of porphyrins has been examined. High resolution spectra were readily obtained with good sensitivity and a detection limit as low as 2 fmol. A mixed solvent system of toluene and ethanol (1:1 by volume) proved to be compatible with the 2,5-dihydroxybenzoic acid (DHB) matrix and solubilized most of the porphyrins examined in this study. Porphyrins which were insoluble in this solvent mixture could be dissolved in an appropriate solvent and deposited on a layer of DHB (layered MALDI). The parent ion was generally the largest peak in the spectrum, although for some metalloporphyrins the peak corresponding to (M – metal + 3H)+ was dominant. The extent of demetallation was found to depend on factors such as sample preparation, the metal ion and the laser intensity. Addition of more than one hydrogen occurred in many cases but was a minor process. Spectra of compounds ionized by different methods showed increasing fragmentation in the order MALDI < layered MALDI < fast-atom bombardment < laser desorption.

SYNTHESIS AND CHARACTERIZATION OF A NOVEL SERIES OF BIS-LINKED DIAZA-18-CROWN-6 PORPHYRINS

The synthesis and physicochemical characterization of a novel family of ‘crowned-porphyrins’ is presented. The compounds uniquely possess a 5,15-di(2-alkylamidophenyl)etioporphyrin bis-linked to the nitrogens on opposite sides of a 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane moiety. The size of the cavity in between the porphyrin and the diaza-18-crown-6 ring has been regulated by varying the length of the alkylamido linking units. The structures of 5 and 7 bear diacetamido linkers whereas 6 is linked via dipropionamido groups. The synthetic pathway presented is generalized such that a wide variety of useful porphyrin-based bis-macrocycles can be prepared. Products have been fully characterized by elemental analysis, mass spectrometry, spectrophotometry, 1H NMR, 13C NMR and 1H–13C heteronuclear correlation NMR spectroscopies. X-Ray structural data are presented for the free-base porphyrin 6 and the ZnII porphyrin 7. The structural data confirm that the porphyrins and their diaza-18-crown-6 substituents adopt cofacial orientations. The size of the cavity between the macrocycles, while demonstrated to accommodate small molecules as shown by the binding of H2O as an axial ligand to the central ZnII ion in the crystal structure of 7, will probably not accommodate large ligands or substrates. Moreover, these compounds should allow sequential metallations to yield heterobimetallic species. Therefore, they are ideally suited for study as model systems for biologically important heme-dependent phenomena such as xenon-129 binding to myoglobin or the mimicking of processes related to the structure and function of cytochrome c oxidase.

Synthesis and structure of a 5,15-bis(4-pyridyl)purpurin

Abstract Base catalyzed cyclization of a 5,15-di(4-pyridyl)octaalkylporphyrin-5-acrylate 6 yields smoothly the corresponding purpurin 2 . Quaternization with methyl iodide yielded the corresponding cationic N,N′-dimethylpyridiniumpurpurin 3 ; X-ray crystallography of purpurin 2 , the first purpurin to be studied crystallographically, shows the two β-alkyl groups on the saturated ring of the purpurin have a syn configuration, and the macrocycle to have a slight saddle shape with a mean deviation of 0.230 A from the least-squares plane calculated for the core atoms.