Gadolinium texaphyrin-methotrexate conjugates. Towards improved cancer chemotherapeutic agents.

Conjugates between methotrexate (MTX, Matrex, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-l-glutamic acid), an antifolate cancer chemotherapeutic to which resistance is often observed, and motexafin gadolinium (MGd), an experimental agent demonstrating selective tumor localization, are described. These systems were prepared in order to test whether linking these two species would produce agents with enhanced activity relative to MTX alone. Both ester- and amide-linked conjugates were synthesized starting from MGd and MTX.

Fine tuning the anion binding properties of 2,6-diamidopyridine dipyrromethane hybrid macrocycles.

The synthesis, characterization, and anion-binding properties of a series of 2,6-diamidopyridine dipyrromethane hybrid macrocycles is presented. As part of this work, a new method for effecting the oxidation of dipyrromethane-based macrocycles in organic solvents has been developed. The macrocyclic frameworks presented here stand out because of their ease of synthesis and tunable anion-binding properties.

Anion binding studies of fluorinated expanded calixpyrroles.

The anion binding properties of fluorinated calix[n]pyrroles (n = 4-6) in aprotic solvents (acetonitrile and DMSO) and modified reaction conditions allowing for the synthesis and isolation of the hitherto missing dodecafluorocalix[6]pyrrole from the condensation of 3,4-difluoro-1H-pyrrole and acetone are described. In acetonitrile solution containing 2% water, the association constants for the 1:1 binding interaction between octafluorocalix[4]pyrrole and chloride anion obtained with isothermal titration calorimetry (ITC) and (1)H NMR titration methods were found to match reasonably well. As compared to its nonfluorinated congener, octafluorocalix[4]pyrrole was found to display enhanced binding affinities for several representative anions in pure acetonitrile as judged from ITC analyses.

Sapphyrins induce apoptosis in hematopoietic tumor-derived cell lines and show in vivo antitumor activity.

Sapphyrins are pentapyrrolic, metal-free, expanded porphyrins. In the present study, the activity of sapphyrins as anticancer agents in hematopoietic-derived tumor cells was explored. It was found that a dihydroxylated water-soluble sapphyrin derivative (PCI-2000) is a potent inducer of apoptosis in a wide variety of tumor cell lines including lymphoma (Ramos, DHL-4, and HF-1), leukemia (Jurkat and HL-60), and myeloma (8226/S, 1-310, C2E3, and 1-414).

Facile syntheses of quater-, penta-, and sexipyrroles.

alpha,alpha-Linked oligopyrroles are attractive precursors for both expanded porphyrin and conducting polymer chemistry. We demonstrate facile methods for synthesizing quater-, penta-, and sexipyrroles from more readily available bi- and terpyrrole intermediates. These products demonstrate stability in their brightly colored oxidized forms, while reduction using borohydride reagents gives the corresponding all-pyrrole oligomers, which oxidize readily in air.

Electronic structure, spectra, and magnetic circular dichroism of cyclohexa-, cyclohepta-, and cyclooctapyrrole.

Three recently obtained expanded porphyrins represent nice examples of compounds for which the electronic and spectral properties can be predicted from symmetry considerations alone. Perimeter-model-based theoretical analysis of the electronic structure of doubly protonated cyclo[6], cyclo[7], and cyclo[8]pyrrole leads to the anticipation of qualitatively the same electronic absorption and magnetic circular dichroism patterns for all three compounds. These predictions are fully confirmed by experiments, as well as DFT and INDO/S calculations.

Straightforward synthesis of sulfur bridged oligopyrrolic macrocycles.

Di- and trisulfide linked oligopyrrolic macrocycles are obtained when appropriate alpha,alpha'-free pyrrolic precursors are reacted with sulfur dichloride; these systems represent the first examples of what might be a general new class of porphyrin analogues.

Functionalized base-pairs: versatile scaffolds for self-assembly.

This article discusses the development of synthetic supramolecular systems derived from hydrogen bond driven base-pairing, with a focus on the self-assembly of individual nucleobase analogues.

Synthesis and photophysics of a porphyrin-fullerene dyad assembled through Watson-Crick hydrogen bonding.

A novel porphyrin-fullerene dyad assembled through Watson-Crick hydrogen bonds is described; this system undergoes photoinduced electron transfer upon irradiation with visible light to produce a charge separated state that is substantially longer lived than that of previous dyads of this type.

A Schiff base expanded porphyrin macrocycle that acts as a versatile binucleating ligand for late first-row transition metals.

The coordination chemistry of the Schiff base polypyrrolic octaaza macrocycle 1 toward late first-row transition metals was investigated. Binuclear complexes with the divalent cations Ni(II), Cu(II), and Zn(II) and with the monovalent cation Cu(I) were prepared and characterized. Air oxidation of the Cu(I) ions in the latter complex to their divalent oxidation state resulted in a change in the coordination mode relative to the macrocycle.

Cis- and trans-strapped calix[4]pyrroles bearing phthalamide linkers: synthesis and anion-binding properties.

[reaction: see text] New cis-strapped calix[4]pyrrole derivatives 12, 13, and 19 and trans-strapped systems 14 and 15 bearing isophthalate-derived diamide spacers linked to the tetrapyrrolic core have been synthesized and characterized by spectroscopic means. The anion-binding behavior of these receptors was investigated by proton NMR spectroscopy and isothermal titration calorimetry (ITC). A 2:1 binding stoichiometry was observed under the conditions of NMR analysis but not at the lower concentration regime used for ITC.

Anion-binding behavior of hybrid calixpyrroles.

Hybrid calixpyrrole systems are calixpyrrole-like macrocycles that are based on more than one type of small molecule building block. Structurally, these "mixed-breed" macrocycles differ from calixpyrroles in that some pyrrolic units in the latter are replaced by other hetereocyclic units such as furan, thiophene, bipyrrole, and bithiophene. Although several such systems have been reported in recent years, only a few have been studied as possible anion receptors.

Calix[4]bipyrrole--a big, flexible, yet effective chloride-selective anion receptor.

Anion binding studies reveal that, in spite of its big size and flexible structure, calix[4]bipyrrole shows strong anion binding in general and good selectivity towards chloride anion in acetonitrile.

Calix[n]bispyrrolylbenzenes: synthesis, characterization, and preliminary anion binding studies.

A series of novel calixpyrrole-like macrocycles, calix[n]bis(pyrrol-2-yl)benzene (calix[n]BPBs, n=2-4) 9 a-11 a, have been synthesized by means of the TFA-catalyzed condensation reaction of bis(pyrrol-2-yl)benzene 8 a with acetone. Calix[2]BPB 9 a represents an expanded version of calix[4]pyrrole in which two of the four meso bridges are replaced by benzene rings. By contrast, systems 10 a and 11 a, which bear great considerable to calixbipyrroles 2 and 3, represent higher homologues of the basic calix[n]BPB motif.

Tetra-TTF calix[4]pyrrole: a rationally designed receptor for electron-deficient neutral guests.

A calix[4]pyrrole incorporating four appended tetrathiafulvalene (TTF) units has been synthesized, and its receptor abilities toward neutral electron-deficient guests, such as 1,3,5-trinitrobenzene, tetrafluoro-p-benzoquinone, and tetrachloro-p-benzoquinone, have been studied in solution by UV-vis and 1H NMR spectroscopies as well as in the solid-state by X-ray crystallography. In its 1,3-alternate conformation a 1:2 sandwich-like complex-stabilized by charge transfer and hydrogen bonding interactions-is formed between the tetra-TTF calix[4]pyrrole and the guest molecules. However, upon addition of chloride ions to the complex the 1,3-alternate conformation is changed in favor of a cone conformation which serves to effect a release of the guests from the tetra-TTF calix[4]pyrrole.

Calix[4]pyrrole[2]carbazole: a new kind of expanded calixpyrrole.

The synthesis and anion binding properties of a new class of calixpyrrole analogue, containing two carbazole subunits in lieu of two of the four acetone bridging elements normally found in calix[4]pyrrole, is described. The compound exists in a winglike structure in the solid state, as judged from single-crystal X-ray diffraction analyses of both the free system and the corresponding benzoate anion complex. Evidence for anion binding in dichloromethane solution was obtained from static fluorescent quenching experiments; these latter revealed a slight preference for acetate relative to other carboxylate anions (e.

Calix[4]phyrins. Effect of peripheral substituents on conformational mobility and structure within a series of related systems.

A new, stepwise synthesis of calix[4]phyrins is described. It relies on the condensation of a ketone with pyrrole to form a dipyrromethane containing a quaternary carbon center that is subsequently condensed with an aromatic aldehyde. This methodology, in contrast to the previous rational approach described by this group (involving formation of a trisubstituted dipyrromethane via the condensation of an aldehyde with pyrrole, followed by condensation of this dipyrromethane with acetone), allows for a variety of bulky, ketone-derived substituents to be incorporated into the meso-like positions.

Synthesis and characterization of a discotic uranium-containing liquid crystal.

The synthesis of several UO(2)-alaskaphyrin derivatives functionalized with aliphatic chains is described. These compounds are found to be liquid-crystalline and form columnar mesophases, as judged from polarizing optical microscopy studies, and represent the first uranium-containing discotic mesogens.

Enhancing Hoogsteen interactions: a pyrrole-containing purine nucleoside that competes with guanosine self-assembly.

A pyrrole-appended purine nucleoside 1 is described that can form an "extended" three-point Hoogsteen-type interaction due to the stabilization of the donor-acceptor-acceptor (DAA) motif. Nucleoside 1 is shown to bind guanosine 10 (a classic ADD motif) to form ensemble I. This interaction competes effectively with guanosine self-assembly and, as such, is capable of disrupting guanosine quadruplex formation.

Biodistribution assessment of a lutetium(III) texaphyrin analogue in tumor-bearing mice using NIR Fourier-transform Raman spectroscopy.

The use of near-infrared (NIR)-excited Fourier-transform (FT) Raman spectroscopy as a technique for evaluating the extent of photosensitizer localization in tumor (human pancreatic adenocarcinomas)-bearing mice has been tested using lutetium(III) texaphyrin analogue Lu-T2B2Tex. The complex was injected subcutaneously in the form of three injections given during the course of 3 days. The kinetics of biodistribution were then followed over a time scale of 1-6 days.

Synthesis and study of a new diamidodipyrromethane macrocycle. An anion receptor with a high sulfate-to-nitrate binding selectivity.

A new 2,6-diamidopyridinedipyrromethane hybrid macrocycle () has been synthesized that shows a high selectivity for dihydrogen phosphate and hydrogen sulfate relative to nitrate in acetonitrile solution as judged from UV-vis spectrophotometric titrations; this leads to the suggestion that this or related systems might find use in nuclear waste remediation applications requiring the selective removal of hydrogensulfate from nitrate-rich waste mixtures.

Octaethylporphyrin and expanded porphyrin complexes containing coordinated BF2 groups.

In contrast to octaethylporphyrin, which forms a very labile bis-BF(2) complex, treatment of the hexa- and octapyrrolic expanded porphyrins amethyrin and [32]octaphyrin with BF(3).Et(2) under standard reaction and work-up conditions gives rise to stable, non-labile mono- and bis-BF(2) complexes; these were readily characterised by, inter alia, X-ray diffraction analyses.