Porphyrins bearing specific patterns of substituents are crucial building blocks in biomimetic and materials chemistry. We have developed methodology that avoids statistical reactions, employs minimal chromatography, and affords up to gram quantities of regioisomerically pure porphyrins bearing predesignated patterns of up to four different meso substituents. The methodology is based upon the availability of multigram quantities of dipyrromethanes. A procedure for the diacylation of dipyrromethanes using EtMgBr and an acid chloride has been refined. A new procedure for the preparation of unsymmetrical diacyl dipyrromethanes has been developed that involves (1) monoacylation with EtMgBr and a pyridyl benzothioate followed by (2) introduction of the second acyl unit upon reaction with EtMgBr and an acid chloride. The scope of these acylation methods has been examined by preparing multigram quantities of diacyl dipyrromethanes bearing a variety of substituents. Reduction of the diacyl dipyrromethane to the corresponding dipyrromethane-dicarbinol is achieved with NaBH(4) in methanolic THF. Porphyrin formation involves the acid-catalyzed condensation of a dipyrromethane-dicarbinol and a dipyrromethane followed by oxidation with DDQ. Optimal conditions for the condensation were identified after examining various reaction parameters (solvent, temperature, acid, concentration, time). The conditions identified (2.5 mM reactants in acetonitrile containing 30 mM TFA at room temperature for <7 min) provided reaction without detectable scrambling (LD-MS) for aryl-substituted dipyrromethanes, and trace scrambling for alkyl-substituted dipyrromethanes. The desired porphyrins were obtained in 14-40% yield. The synthesis is compatible with diverse functionalities: amide, aldehyde, carboxylic acid, ester, nitrile, ether, bromo, iodo, ethyne, TMS-ethyne, TIPS-ethyne, perfluoroarene. In total 30 porphyrins of the types A(3)B, trans-A(2)B(2), trans-AB(2)C, cis-A(2)B(2), cis-A(2)BC, and ABCD were prepared, including >1-g quantities of three porphyrins.

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The condensation of an aldehyde with a dipyrromethane bearing a sterically unhindered aryl substituent at the 5-position typically results in low yield and a mixture of porphyrin products derived from acidolytic scrambling. We have developed a concise nonscrambling synthesis of such trans-porphyrins that takes advantage of the availability of multigram quantities of dipyrromethanes. This route involves the selective monoacylation of the dipyrromethanes with a pyridyl thioester, reduction of the monoacyl dipyrromethane to the corresponding carbinol, and self-condensation of the carbinol to form the porphyrin. The monoacylation procedure has wide scope as demonstrated by the preparation of a set of 15 diverse monoacyl dipyrromethanes in good yield at the multigram scale. The dipyrromethanecarbinol self-condensation reaction is extremely rapid (<3 min) under mild room-temperature conditions and affords the trans-porphyrin in 16-28% yield. Analysis by laser-desorption mass spectrometry (LD-MS) of samples from the crude reaction mixture revealed no scrambling within the limit of detection (1 part in 100). The self-condensation is compatible with a range of electron-withdrawing or -releasing substituents as well as substituents for building block applications (TMS-ethyne, ethyne, iodo, ester). The absence of any detectable scrambling in the self-condensation enables a simple purification. The synthesis readily affords gram quantities of pure, sterically unhindered trans-porphyrins in a process involving minimal chromatography.

ABSTRACT:The successful use of dipyrromethanecarbinols in rational routes to porphyrinic macrocycles requires catalysis conditions that enable irreversible condensation, thereby avoiding substituent scrambling and formation of undesired porphyrin products. Previously, successful conditions of trifluoroacetic acid (TFA) (30 mM) in acetonitrile were identified following a lengthy survey of TFA and BF 3 -etherate catalysis in diverse solvents. In this study, focus was placed on the acid catalyst by examining 17 acids in CH 2 Cl 2 , the traditional solvent for two-step, one-flask porphyrin syntheses. In the self-condensation of the carbinol derived from 1-(4-methylbenzoyl)-5-phenyldipyrromethane, porphyrin yields of 9-55% were obtained from the various acids, compared to 20% under TFA catalysis in acetonitrile. A number of catalytic conditions that produce little to no porphyrin in reactions of pyrrole benzaldehyde afforded good yields of porphyrin and the suppression of scrambling in reactions of dipyrromethanecarbinols. The four best acid catalysts (InCl 3 , Sc(OTf) 3 , Yb(OTf) 3 , and Dy(OTf) 3 ) initially identified were then examined with dipyrromethanecarbinols bearing challenging substituents (alkyl, pyridyl, or no substituent). The greatest improvement was obtained with the pyridyl substrates. Selected reactions performed on a preparative scale (115 to 460 mg of isolated porphyrin) verified the results of the analytical-scale experiments and revealed the more facile isolation of the porphyrin from reactions performed in CH 2 Cl 2 rather than acetonitrile. This study provides alternatives to the use of TFA/acetonitrile that offer advantages in terms of yield and isolation of the porphyrin without sacrificing suppression of scrambling. Furthermore, the finding that poor catalysts for the benzaldehyde pyrrole reaction can be excellent catalysts for dipyrromethanecarbinols provides guidance for the identification of other catalysts for use with reactive precursors in porphyrin-forming reactions.

Two porphyrin-based optoelectronic gates and several prototypical redox-switching components of gates have been synthesized for studies in molecular photonics. Linear and T-shaped molecular optoelectronic gates contain a boron-dipyrrin (BDPY) dye as the input unit, a zinc (Zn) porphyrin as the transmission unit, a free base (Fb) porphyrin as the output unit, and a magnesium (Mg) porphyrin as the redox-switching unit. The linear gate and T gate were synthesized using a molecular building block approach. In the linear gate synthesis, a BDPY−Zn porphyrin dyad was coupled with a Fb porphyrin−Mg porphyrin dimer. The synthesis of the T gate utilized a Zn porphyrin bearing four different meso substituents:  mesityl, 4-iodophenyl, 4-[2-(trimethylsilyl)ethynyl]phenyl, and 4-[2-triisopropyl)ethynyl]phenyl. Attachment of the three different groups to the Zn porphyrin was accomplished using successive Pd-mediated coupling reactions in the following sequence:  Fb porphyrin (output unit), BDPY dye (input unit), and Mg porphyrin (redox-switching unit). Both the linear gate and T gate syntheses introduce the Mg porphyrin at the final step to minimize demetalation of the Mg porphyrin. Refinements to various components of these gates were investigated through the preparation of a ferrocene−porphyrin, a ferrocene−phthalocyanine, and a ferrocene−porphyrin−phthalocyanine. A dyad motif for studies of optically based redox switching was prepared that contains a derivative of Ru(bpy)3X2 coupled to a porphyrin. From these and related studies have emerged a number of design considerations for the development of refined optoelectronic gates.

XML-enabled publish-subscribe (pub-sub) systems have emerged as an increasingly important tool for e-commerce and Internet applications. In a typical pub-sub system, subscribed users specify their interests in a profile expressed in the XPath language. Each new data content is then matched against the user profiles so that the content is delivered only to the interested subscribers. As the number of subscribed users and their profiles can grow very large, the scalability of the service is critical to the success of pub-sub systems. In this article, we propose a novel scalable filtering system called iFiST that transforms user profiles of a twig pattern expressed in XPath into sequences using the Prüfer's method. Consequently, instead of breaking a twig pattern into multiple linear paths and matching them separately, FiST performs holistic matching of twig patterns with each incoming document in a bottom-up fashion. FiST organizes the sequences into a dynamic hash-based index for efficient filtering, and exploits the commonality among user profiles to enable shared processing during the filtering phase. We demonstrate that the holistic matching approach reduces filtering cost and memory consumption, thereby improving the scalability of FiST.

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This report enables a novel approach for optimizing the utility of zebrafish in drug discovery and drug delivery research.