5'-Vitamin B12 derivatives suitable for bioconjugation via the amide bond.

Vitamin B12 is an attractive candidate for a drug or an imaging-agent carrier into cells, due to its dietary uptake and well established transport through glycoproteins. Utilization of this system requires an appropriate functionalization of vitamin B12 that both allows for the conjugation of therapeutics and does not interrupt its recognition by transport proteins. Modifications at the 5'-position on the ribose moiety are among a few approaches which meet the criteria. In this article we present vitamin B12 derivatives bearing either the amino or the carboxylic group at the 5'-position. The presence of these functional groups enables conjugation of biologically important molecules to vitamin B12via the amide bond. The established method is not only limited to organic media but also works in an aqueous environment, giving the desired products in very good yields.

Electrochemistry and catalytic properties of amphiphilic vitamin B12 derivatives in nonaqueous media.

The reduction pathway of cobalester (CN)Cble, an amphiphilic vitamin B12 derivative, was investigated in organic solvents under electrochemical conditions and compared with mono- and dicyanocobyrinates. The redox characteristics were determined using cyclic voltammetry and spectroelectrochemical methods. The presence of a nucleotide moiety in B12-derivative impedes the in situ formation of dicyano-species thus facilitating the (CN)Co(iii) to Co(i) reduction. The (CN)Cble shows stepwise reduction to Co(i) via (CN)Co(ii). The reduction of (CN)Co(ii)/Co(i) was found to depend on cyanide-solvent exchange equilibrium with weakly coordinating solvents and bulky peripheral chains promoting intact (CN)Co(ii) species existence. The studied complexes were also utilized as catalysts in bulk electrolysis of benzyl bromide affording bibenzyl in very good yield.

An amphiphilic, catalytically active, vitamin B12 derivative.

We performed the reaction of vitamin B12 with N,N-dimethylformamide dimethyl acetal for primary amide activation, and added MeOH as a nucleophile, to afford cobalester, the first amphiphilic cobalamin derivative. The unique combination of redox properties and solubility represents an asset for its use as a catalyst in C-C bond forming reactions.

A simple and versatile one-pot synthesis of meso-substituted trans-A2B-corroles.

We have developed a new methodology that affords regioisomerically pure trans-A2B-corroles. The corrole formation reaction involves the acid-catalyzed condensation of a dipyrromethane and an aldehyde followed by oxidation with DDQ. Optimal conditions for the condensation were identified after examining various reaction parameters (solvent, acid, concentration, time). The conditions identified (CH2Cl2, [DPM] = 33 mM, [aldehyde] = 17 mM, [TFA] = 1.3 mM (for sterically hindered DPMs) or [TFA] = 0.26 mM (for sterically unhindered DPMs), 5 h, room temperature) resulted in the formation of corroles in 3-25% yield without detectable scrambling. The synthesis is compatible with diverse functionalities: ester, nitrile, ether, fluoro, hydroxy, iodo, nitro, thioacetate, methylsulfoxy. In total 21 corroles of type trans-A2B were prepared. Three exemplary corrole syntheses were successfully carried out at 8 mmol scale. Corroles 23, 30, and 41 (160-600 mg) were obtained in essentially the same yield as in small scale experiments.

Synthesis of thiol-derivatized europium porphyrinic triple-decker sandwich complexes for multibit molecular information storage

The storage of multiple bits of information at the molecular level requires molecules with a large number of distinct oxidation states. Lanthanide triple-decker sandwich molecules employing porphyrins and phthalocyanines afford four cationic states and are very attractive for molecular information storage applications. Five triple-decker building blocks have been prepared of the type (phthalocyanine)Eu(phthalocyanine)Eu(porphyrin), each bearing one iodo, one ethyne, or one iodo and one ethyne group attached to the porphyrin unit. Two triple-decker building blocks with different oxidation potentials were derivatized with an S-acetylthiophenyl unit for attachment to an electroactive surface. To explore the preparation of arrays comprised of triple deckers, which may lead to the storage of a larger number of bits, two types of dyads of triple deckers were prepared. An ethyne-linked dyad of triple deckers bearing one S-acetylthiophenyl unit was prepared via repetitive Sonogashira couplings, and a butadiyne-linked dyad was prepared via a modified Glaser coupling. The triple deckers were characterized by absorption spectroscopy, laser-desorption mass spectrometry, and (1)H NMR spectroscopy. The thiol-derivatized triple deckers form self-assembled monolayers (SAMs) on gold via in situ cleavage of the thiol protecting group. The SAM of each array is electrochemically robust and exhibits three well-resolved, reversible oxidation waves. These electrochemical characteristics indicate that these types of molecules are well suited for storing multiple bits of information.