Interplay between acetate ions, peripheral groups, and reactivity of the core nitrogens in transmetalation of tetrapyrroles

The mechanism of acetate-assisted transmetalation of tetrapyrroles was investigated in a model system consisting of chlorophyll a and copper(II) acetate in organic solvents by using a spectroscopic and kinetic approach. Surprisingly, acetate ions bind to the central Mg in chlorophyll much more strongly than do acetonitrile, methanol and even pyridine, one of the best ligands in chlorophyllic systems. This exceptionally strong non-symmetrical axial ligation of the central Mg by acetate causes its out-of-plane displacement and deformation of the tetrapyrrole ring, thus facilitating the interaction with an incoming CuII complex. This mechanism is controlled by a keto-enol tautomerism of the chlorophyll isocyclic ring. Additionally, depending on solvent, acetate activates the incoming metal ions. These new insights allow to suggest a mechanism for the acetate method of metal exchange in tetrapyrrolic macrocycles, which resembles biological insertion of metal ions into porphyrins. It also provides a guideline for the design of more efficient methods for the metalation of porphyrins and related macrocycles.     

QSAR of genotoxic active benzazoles

Previously synthesized 2,5-disubstituted benzoxazole and benzimidazole derivatives, were tested for their genotoxic activity in the Bacillus subtilis rec- assay. The results revealed that 5-methyl-2-(p-aminobenzyl)benzoxazole exhibited the highest genotoxic response, which was comparable to 4-nitroquinoline 1-oxide (4-NQO), the reference agent of classical positive mutagen. Among the other tested compounds, four showed a genotoxic activity. A QSAR study revealed that structural parameters IY(C(2)H(4)) and IY(CH(2)O), indicating the bridge elements between the phenyl moiety and the fused ring system at position 2 and the quantum chemical parameter (DeltaE ), showing the difference between HOMO and LUMO energies, were found significant for enhancing the genotoxic activity in these compounds. In addition, the substituent effects on positions R and R(1) were found important for the activity as well as holding a substituent possessing a maximum length with a minimum width property on position R(1) like alkyl groups. On the other hand, substituting position R with an electron donating group instead of electron withdrawing group increased the genotoxic activity.     

On the negligible impact of ruffling on the electronic spectra of porphine, tetramethylporphyrin, and perfluoroalkylporphyrins.

In the first part of this paper, the syntheses, structural characterization, molecular modeling, and electronic spectra for planar and nonplanar perfluoroalkylated porphyrins, (R(f))(4)P's, are reported. These studies demonstrate that the intrinsic substituent effect of the perfluoroalkyl group on the long-wavelength electronic spectrum of porphyrins is substantial, and similar (in magnitude) to that of a phenyl ring. Moreover, it is shown that out-of-plane distortion of (R(f))(4)P's has a negligible impact on their electronic spectra. These data bolster the findings of our earlier work and demonstrate that nonplanarity of (R(f))(4)P's does not result in a red-shift in their optical spectra. In the second part of this paper, time-dependent density functional spectral calculations (B3LYP/6-311G/TD) for porphine, 5,10,15,20-tetrakis(trifluoromethyl)porphyrin, and 5,10,15,20-tetramethylporphyrin in a variety of ruffled conformations are reported. The results of these studies indicate that (1) substantial ruffling of porphyrins has a negligible effect upon their electronic spectra, (2) similarly small effects upon electronic spectra are predicted if electron-withdrawing or electron-releasing groups decorate the porphyrin periphery, (3) for sterically encumbered porphyrins, ruffling can actually result in hypsochromic shifts in various absorption bands, and (4) the bulk of the red-shift commonly thought to be due to nonplanar distortion actually arises from other substituent effects. These results pose serious challenges to previous theoretical and empirical studies that have sought to find a cause-and-effect relationship between nonplanarity and electronic spectra in porphyrins.     

The NMR spectra of porphyrins—19: 13C and proton NMR spectra of metal-free porphyrins with the Type-IX substituent orientation,and of their zinc(II) complexes

The ¹³C and proton NMR spectra of six porphyrins bearing the substituent orientation characteristic of the natural “Type-IX” arrangement are reported and assigned. Significant concentration effects in the spectra of the free base porphyrins, together with the broadening of the C_α (and occasionally C_β) carbon resonances due to NH tautomerism caused a significant loss of data in these spectra. However, the spectra of the corresponding zinc(II) porphyrins (with addition of excess pyrrolidine) show that both these extraneous effects are completely removed to give well-resolved spectra with accurately reproducible chemical shifts. These spectra are assigned and an analysis of the chemical shifts allows the deduction of substituent chemical shift (SCS) parameters for the peripheral substituents at the beta and meso carbons. There is no global effect of these beta substituents, the beta carbon SCS being confined to the immediate pyrrole ring, and the meso carbon SCS to the two adjacent pyrrole rings. The SCS parameters are analyzed and it is shown how they can be used to predict the peripheral and meso carbon chemical shifts of any porphyrin bearing the substituents discussed.     

Modulation of the porphyrin inner proton exchange rates by the steric effects of bridge substitution

The tautomeric equilibria and H-N proton transfer taking place in the nonsymmetrically substituted water-soluble 2-sulfonato-5,15-bis(4-sulfonatophenyl)porphyrin (1) and in its 10-bromo-substituted derivative (2) were analyzed by NMR methods: 1H and 13C spectroscopies and heteronuclear multiple bond correlation (HMBC) and heteronuclear single quantum coherence (HSQC) 1H-13C and 1H-15N techniques. The existence of preferred pathways of H-N transfer was detected. The conclusions are rationalized by taking into account the effect partial meso-substitution exerts on the relative energies of the different cis-tautomer intermediates involved in the tautomerism. These results underline the experimental consequences stemming from the nonequivalence in porphyrins between the 'tautomeric interconversion' and 'proton transfer' terms, when observed by NMR techniques, as a consequence of the existence of two pairs of degenerate tautomers and transformation pathways.     

Protease-mediated fragmentation of p-amidobenzyl ethers: a new strategy for the activation of anticancer prodrugs

A new anticancer prodrug activation strategy based on the 1,6-elimination reaction of p-aminobenzyl ethers is described. Model studies were undertaken with the N-protected peptide benzyloxycarbonyl-valine-citrulline (Z-val-cit), which was attached to the amino groups of p-aminobenzyl ether derivatives of 1-naphthol and N-acetylnorephedrine. The amide bond that formed was designed for hydrolysis by cathepsin B, a protease associated with rapidly growing and metastatic carcinomas. Upon treatment with the enzyme, the Z-val-cit-p-amidobenzyl ether of 1-naphthol (2) underwent peptide bond hydrolysis with the rapid release of 1-naphthol. The aliphatic Z-val-cit-p-amidobenzyl ether of N-acetylnorephedrine (5) also underwent amide bond hydrolysis, but without the ensuing elimination of N-acetylnorephedrine. On the basis of these results, the phenolic anticancer drugs etoposide (6) and combretastatin A-4 (7) were attached to the Z-val-cit-p-amidobenzyl alcohol through ether linkages, forming the peptide-drug derivatives 8 and 9, respectively. Both compounds were stable in aqueous buffers and serum and underwent ether fragmentation upon treatment with cathepsin B, resulting in the release of the parent drugs in chemically unmodified forms. The released drugs were 13-50 times more potent than were the prodrug precursors on a panel of cancer cell lines. In contrast, the corresponding carbonate derivative of combretastatin A-4 (13) was unstable in aqueous environments and was as cytotoxic as combretastatin A-4. This result extends the use of the self-immolative p-aminobenzyl group for the fragmentation of aromatic ethers and provides a new strategy for anticancer prodrug development.     

Synthesis, characterization and spectral properties of substituted tetraphenylporphyrin iron chloride complexes

A series of substituted tetraphenylporphyrin iron chloride complexes [RTPPFe(III)Cl, R=o/p-NO?, o/p-Cl, H, o/p-CH?, o/p-OCH?] were synthesized by a novel universal mixed-solvent method and the spectral properties of free base porphyrins and iron porphyrin compounds were compared with each other. The experimental results showed that the one-pot mixed solvent method was superior to the two-step method in the yields, reaction time and workup of reaction mixtures for the synthesis of iron porphyrin compounds. The highest yields (28.7%-40.4%) of RTPPFe(III)Cl were obtained in the mixed solvents propionic acid, glacial acetic acid and m-nitrotoluene under reflux for 2 h. A detailed analysis of ultraviolet-visible (UV-vis), infrared (IR) and far-infrared (FIR) spectra suggested the transformation from free base porphyrins to iron porphyrins. The red shift of the Soret band in ultraviolet-visible spectra due to the presence of p-nitrophenyl substituents and the blue shift of Fe-Cl bond of TPPFeCl in far-infrared spectra were further explained by the electron transfer and molecular planarity in the porphyrin ring.     

The mixed-aldehyde synthesis of difunctional tetraarylporphyrins

The synthesis is reported of nine unsymmetrical, meso-substituted porphyrins. Among the compounds prepared are the following 5-(R)-10,15,20-tri-p-tolylporphyrins; R = 2,6-dinitrophenyl, 4-hydroxy-3-ethoxy-phenyl, 4-hydroxy-3-methoxy-5-nitrophenyl, 5-hydroxy-2-nitrophenyl and 4-hydroxy-3-nitrophenyl. Other porphyrins reported include 5-(2-(1-butoxy)phenyl)-15-(2-nitrophenyl)-10-15-di-p-tolylporphyrin and the two 5-(R)-10-15,20-tripropylporphyrins in which R = 2-nitrophenyl and 2-hydroxyphenyl. The disubstituted porphyrins offer a rational route to the synthesis of difunctional “tailed-porphyrins”.     

Theoretical study of the inner hydrogen migration in the β-substituted 5,10,15,20-tetraphenylporphyrins

In order to investigate the mechanism of the N-H migration in asymmetrical metal-free porphyrins, four porphyrins of electron-withdrawing or electron-donating substituent at the β-position were studied theoretically. For porphyrin 2 (R = OMe), 3 (R = Me), and 4 (R = NO(2)), four different asynchronous N-H migration pathways exist due to symmetry reasons. The corresponding trans-, cis-, and transition state geometries were analyzed using a normal structure decomposition method. Our data show that the hydrogen migration of porphyrin 2, 3, and 4 in clockwise (A, B) are much more preferred than counterclockwise (C, D) direction.     

Rational or statistical routes from 1-acyldipyrromethanes to meso-substituted porphyrins. Distinct patterns, multiple pyridyl substituents, and amphipathic architectures

New methodology is described for the synthesis of porphyrins bearing four (A 4, cis-A 2B 2, cis-ABC 2, trans-A 2B 2) or fewer (A, cis-AB, cis-A 2, trans-A 2) meso substituents. The method entails condensation of two 1-acyldipyrromethanes in the presence of a metal salt (MgBr 2, 3 mol equiv) and a noncoordinating base (DBU, 10 mol equiv) in a noncoordinating solvent (toluene) with heating (conventional or microwave irradiation) and exposure to air. The rational synthesis of trans-A 2B 2- or trans-A 2-porphyrins was achieved via condensation of two identical 1-acyldipyrromethanes. The statistical synthesis of various meso-substituted porphyrins was achieved via condensation of two nonidentical 1-acyldipyrromethanes. Both routes possess attractive features including (1) no scrambling, (2) good yield (up to 60%) at high concentration (100 mM) for the macrocycle-forming step, (3) reasonable scope (aryl, heteroaryl, alkyl, or no substituent), (4) short reaction time ( approximately 2 h) via microwave irradiation, (5) magnesium porphyrins as the products, which easily undergo demetalation, and (6) facile chromatographic purification. A key advantage of the statistical route is to obtain a cis-substituted porphyrin without the corresponding trans isomer. For example, reaction of an A/B-substituted 1-acyldipyrromethane and the fully unsubstituted 1-formyldipyrromethane gave the magnesium chelates of three porphyrins: the trans-A 2B 2-porphyrin, the "hybrid" cis-AB-porphyrin, and porphine (no trans-AB-porphyrin can form), which were readily demetalated and separated as the free base species. Altogether 26 1-acyldipyrromethanes and 26 target porphyrins have been prepared, including many with two different pyridyl substituents. One set of amphipathic porphyrins includes cis-A 2B 2- or cis-A 2BC-porphyrins wherein A = pentyl and B/C = pyridyl ( o-, m-, p-). Taken together, the rational and statistical routes enable facile conversion of readily available 1-acyldipyrromethanes to diverse porphyrins bearing 1-4 meso substituents for which access is limited via other methods.     

烯醇-酮互变异构型亚胺衍生物对Co2+的高选择性识别

设计合成了新型烯醇-酮互变异构型亚胺衍生物R, 考察了受体R对18种阳离子的紫外光谱及裸眼识别性能. 结果表明, 该受体对Co²⁺, Fe²⁺和Ni²⁺表现出良好的紫外光谱识别能力, 且可实现对Co²⁺相对明显的裸眼单一识别. Job曲线表明, 受体R与Co²⁺形成了1:1型金属配合物, 且检出限可达4.14×10^-7 mol/L. 制备了受体R裸眼比色识别试纸; 根据理论计算及核磁滴定实验结果阐述了Co²⁺离子识别过程中烯醇-酮互变异构机理.     

One‐Dimensional,Cofacial Porphyrin Polymers Formed by Self‐Assembly of meso‐Tetrakis(ERE Donor) Zinc(II) Porphyrins

A series of meso‐tetrakis‐(ERE donor) zinc(II) porphyrins n Zn (ERE donor=4‐R‐3,5‐bis[(E)‐methyl]phenyl; 1 Zn: E=NMe₂, R=Br; 2 Zn: E=NMe₂, R=H; 3 Zn: E=OMe, R=Br; 4 Zn: E=OMe, R=H) have been synthesized in excellent yields. As a result of the combination of a Lewis acidic site and eight Lewis basic sites within one molecule, monomeric molecules of n Zn self‐assemble to form one‐dimensional porphyrin polymers [ n Zn]_∞ in the solid state, as confirmed for 1 Zn and 3 Zn by X‐ray crystallography. The coordination environment around the zinc(II) ions in these polymers is octahedral. They are ligated by four equatorial nitrogen atoms of the porphyrin and two apical E atoms (E=N, O) provided by the EBrE donor groups of adjacent n Zn molecules. Complexes 2 Zn and 4 Zn did not form single crystals, but solid‐state UV/Vis analysis points to the formation of similar structures. Solution UV/Vis and ¹H NMR spectroscopy indicated that interactions between 1 Zn and 2 Zn monomers in the polymers are stronger than between 3 Zn and 4 Zn monomers. Interestingly, they also revealed that the presence of a neighboring bromine atom in the EBrE donor groups has a considerable influence on the coordination properties of the benzylic N or O atoms. The zinc(II) ions of the porphyrins most likely adopt only hexacoordination in the solid state, owing to the unique predisposition of Lewis acidic and basic sites in the n Zn molecules. Several parameters of the aggregates, for example, the interplanar separation between porphyrins and the zinc–zinc distances, change as a function of the coordinating E groups. The high degree of modularity in their synthesis makes these zinc(II) porphyrins an interesting new entry in noncovalent multiporphyrin assemblies.     

Classical versus redox tautomerism: substituent effects on the keto/enol and sulfoxide/sulfenic acid equilibria

MP2/6-311+G** ab initio calculations have been carried out for a classical example of tautomerism, the keto/enol [RCOCH₃/RC(OH)CH₂] and an example of redox tautomerism, the sulfoxide/sulfenic acid [RS(O)H/RSOH]. Eleven R substituents have been examined. Both equilibria show proportional energies and similar dependence on the Swain-Lupton Fand Rparameters.     

Structural and photophysical studies of trans-AB(2)C-substituted porphyrin ligands and their zinc and copper complexes

trans-AB(2)C porphyrins with A = C(6)H(4)-COOR, C = C(6)H(4)-NX(2) and B = C(6)H(5) (R = CH(3), H; X = O, H) have been synthesised by a rational high-yield procedure (1a-1d) and their zinc(ii) and copper(ii) complexes have been prepared (2a-2d, 3a-3d ).1a, 2a .THF and 3a display different distortions of the porphyrin core as shown by single crystal X-ray crystallography and NSD analyses. The Soret and Q bands of free-base and metalated porphyrins with mixed electron donating and withdrawing substituents (NH(2)/COOR) are red-shifted as are the corresponding emission bands of free-base and zinc porphyrins. The electronic asymmetry revealed by spectrocopy is rationalised by DFT calculations.     

2-氨基取代噻唑基膦酸脂的合成

本文报导一系列2-氨基-5-取代-4-噻唑基膦酸酯和2-氨基-4-取代-5-噻唑基膦酸酯的合成. 这类化合物显示了一定的杀菌活性.     

Dehydrogenation versus oxygenation in two-electron and four-electron reduction of dioxygen by 9-alkyl-10-methyl-9,10-dihydroacridines catalyzed by monomeric cobalt porphyrins and cofacial dicobalt porphyrins in the presence of perchloric acid

Dehydrogenation of 10-methyl-9,10-dihydroacridine (AcrH(2)) by dioxygen (O(2)) proceeds efficiently, accompanied by the two-electron and four-electron reduction of O(2) to produce H(2)O(2) and H(2)O, which are effectively catalyzed by monomeric cobalt porphyrins and cofacial dicobalt porphyrins in the presence of perchloric acid (HClO(4)) in acetonitrile (MeCN) and benzonitrile (PhCN), respectively. The cobalt porphyrin catalyzed two-electron reduction of O(2) also occurs efficiently by 9-alkyl-10-methyl-9,10-dihydroacridines (AcrHR; R = Me, Et, and CH(2)COOEt) to yield 9-alkyl-10-methylacridinium ion (AcrR+) and H(2)O(2). In the case of R = Bu(t) and CMe(2)COOMe, however, the catalytic two-electron and four-electron reduction of O(2) by AcrHR results in oxygenation of the alkyl group of AcrHR rather than dehydrogenation to yield 10-methylacridinium ion (AcrH+) and the oxygenated products of the alkyl groups, i.e., the corresponding hydroperoxides (ROOH) and the alcohol (ROH), respectively. The catalytic mechanisms of the dehydrogenation vs the oxygenation of AcrHR in the two-electron and four-electron reduction of O(2), catalyzed by monomeric cobalt porphyrins and cofacial dicobalt porphyrins, respectively, are discussed in relation to the C(9)-H or C(9)-C bond cleavage of AcrHR radical cations produced in the electron-transfer oxidation of AcrHR.     

Amidation of saturated C-H bonds catalyzed by electron-deficient ruthenium and manganese porphyrins. A highly catalytic nitrogen atom transfer process

Amidation of a variety of hydrocarbons with PhI=NTs catalyzed by ruthenium and manganese meso-tetrakis(pentafluorophenyl)porphyrins 1 and 2 afforded N-substituted amides in up to 92% yields with good to excellent substrate conversions. By employing catalyst 2, exceptionally high turnovers (up to 2600) were achieved, and the amidations can be effected by directly using PhI(OAc)(2)/NH(2)R as amidating reagents; in the case of R = COCF(3) a direct amination was realized in up to 90% yield.     

Formation of chiral mesostructured porphyrin-silica hybrids

Formation of a chiral mesostructured porphyrin-silica hybrid with cylindrical helical stacking of anionic porphyrins was achieved by the aid of cationic organosilane. The enantiopurity of the hybrid was dramatically enhanced by a small amount of (R)-1,1'-bi-2-naphthol or its enantiomer.     

New functionalized pyrazolines from 1-aroyl-2-phenylacetylenes and thiocarbonohydrazides

The reaction of 1-aroyl-2-phenylacetylenes with thiocarbonohydrazide and benzaldehyde thiocarbohydrazone in acetic acid-water or ethanol-water systems with the reagents in an equimolar ratio leads to the selective formation of 1-carbothiohydrazinoyl-5-hydroxy-3-phenyl-5-R-2-pyrazolines. Ring-chain tautomerism involving the enamine and hydrazone forms was detected for solutions of the pyrazolines (with R = 2-thienyl) in DMSO. Dedicated to Academician M. G. Voronkov on his 85th birthday. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1655–1661, November, 2006.     

Theoretical calculation on the substituent effect of strontium para-tetraphenyl porphyrins

Structural Chemistry - A series of strontium para-tetraphenyl porphyrins (SrTRPPs) with different electron property substituents (R?=?-NH2, -OCH3, -H, -F, -COOH, -NO2) on the...