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J L Sessler

Publications and source records attributed to J L Sessler.

At least 19 recordsLinked to original sources
PubMed2003

Monomer and polymer quinoxaline derivatives for cationic recognition.

Monomeric and polymeric 5-nitroquinoxaline derivatives disubstituted in the 2 and 3 positions with 2-pyrrolyl (A), 2-furyl (B) and 2-thienyl (C) groups were prepared and characterized. The substituted 5-nitroquinoxalines were used as active components in poly(vinyl chloride)-membrane and electropolymerized electrodes that were then tested as possible sensors for various cationic species. In contrast to the difurylnitroquinoxaline-based systems, the monomeric and polymeric dipyrrolyl- and dithienylquinoxaline electrodes displayed a good selectivity for Ag(+) ions, providing a near-Nernstian response in the 10(-5) to 10(-2) mol L(-1) concentration range. The similar potentiometric behavior displayed by the monomeric and polymeric forms of systems A and C supports the contention that the main binding modes displayed by the monomeric forms are retained in the corresponding polymeric structures.

Journal Article↗
PubMed2001

Room-temperature monoclinic and low-temperature triclinic phase-transition structures of meso-octamethylcalix[4]pyrrole-dimethyl sulfoxide (1/1).

Crystals of the title complex, C28H36N4*C2H6OS, undergo a phase transition between room temperature and 198 K, as determined by X-ray diffraction techniques. A monoclinic form is observed at room temperature, while a triclinic modification is found at 198 K, with Z' changing from 1 to 2. Differential scanning calorimetry (DSC) of the calixpyrrole-dimethyl sulfoxide complex revealed a series of phase changes between 273 and 243 K. The transition from the room-temperature monoclinic form to the low-temperature triclinic form is reversible, as determined by changes in the cell dimensions from remeasuring selected reflections at room temperature and at temperatures below 223 K. The uncomplexed calix[4]pyrrole molecule shows no phase changes occurring between room temperature and 233 K, the low-temperature limit of the DSC.

Calorimetry, Differential Scanning↗
PubMed2001

Synthesis of a metal-free texaphyrin.

The synthesis of a metal-free form of texaphyrin, an aromatic porphyrin-like macrocycle, is described. Previously, texaphyrins could only be obtained reproducibly in the form of metal complexes. Using ferrocenium cation as the oxidizing agent and starting with a reduced porphyrinogen-like nonaromatic form of texaphyrin, we isolated, in good yield, the metal-free oxidized texaphyrin as its HPF(6) salt. This product was characterized by X-ray diffraction analysis, UV-vis spectroscopy, and cyclic voltammetry. [structure: see text]

Crystallography, X-Ray↗
PubMed2001

Redox cycling by motexafin gadolinium enhances cellular response to ionizing radiation by forming reactive oxygen species.

PURPOSE: To examine the mechanism of radiation enhancement by motexafin gadolinium (Gd-Tex) in vitro. METHODS AND MATERIALS: Oxidation of ascorbate and NADPH by Gd-Tex was evaluated in a neutral buffer. Growth inhibition of human uterine cancer cell line MES-SA was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Clonogenic assays were used to measure radiation response in MES-SA, A549 human lung carcinoma, E89, a CHO cell line variant deficient in glucose-6-phosphate dehydrogenase activity, and murine lymphoma cell lines LYAR and LYAS. RESULTS: Gd-Tex catalyzed the oxidation of NADPH and ascorbate under aerobic conditions, forming hydrogen peroxide. Decreased viability was observed in MES-SA cells incubated with Gd-Tex in media containing NADPH or ascorbate. Gd-Tex and ascorbate increased fluorescence in dichlorofluorescin acetate-treated cultures. Synergistic effects on the aerobic radiation response in MES-SA and A549 were seen using Gd-Tex in combination with L-buthionine-(S,R)-sulfoximine (BSO). Incubation with Gd-Tex in the presence of ascorbate increased the aerobic radiation response of E89 and the apoptosis-sensitive B-cell line (LYAS). CONCLUSIONS: Gd-Tex sensitizes cells to ionizing radiation by increasing oxidative stress as a consequence of futile redox cycling. Optimization of the concentration of ascorbate (or other reducing species) may be required when evaluating Gd-Tex activity in vitro.

Animals↗
PubMed2001

Conformational features and anion-binding properties of calix[4]pyrrole: a theoretical study.

The conformational preference of calix[4]pyrrole and its fluoride and chloride anion-binding properties have been investigated by density functional theory calculations. Geometries were optimized by the BLYP/3-21G and BLYP/6-31G methods, and energies were evaluated with the BLYP/6-31+G method. To model the effect of medium, the SCIPCM solvent model was also employed. Four typical conformations of the parent substituent-free calix[4]pyrrole were studied. Both in the gas phase and in CH(2)Cl(2) solution, the stability sequence is predicted to be 1,3-alternate > partial cone > 1,2-alternate > cone. The cone conformation is predicted to be about 16.0 and 11.4 kcal/mol less stable in the gas phase and CH(2)Cl(2) solution, respectively. This is mainly due to electrostatic repulsions arising from the all-syn pyrrole/pyrrole/pyrrole/pyrrole arrangement present in this conformer. The existence of possible 1:1 and 1:2 anion-binding modes were explored in the case of fluoride anion, and the factors favoring the 1:1 binding mode are discussed. The calculated binding energy for fluoride anion is about 15 kcal/mol larger than that for chloride anion. The calculated binding energy for chloride anion agrees with the experimental value very well. The presence of meso-alkyl substituents destabilizes the cone conformer with respect to the 1,3-alternate conformer and, therefore, reduces the anion-binding affinity by 3-4 kcal/mol. The strength of N-H- - -anion hydrogen bonds in the various structures subject to study were estimated on the basis of the calculated anion-binding energies and the predicted structural deformation energies of substituent-free calix[4]pyrrole.

Journal Article↗
PubMed2001

Hydrogen-bond-mediated photoinduced electron-transfer: novel dimethylaniline-anthracene ensembles formed via Watson-Crick base-pairing.

The synthesis of a new, noncovalent anthracene-dimethylaniline dyad (ensemble I) held together via guanosine-cytidine Watson-Crick base-pairing interactions is reported. Upon excitation at 420 nm, photoinduced electron-transfer from the dimethylaniline donor to the singlet excited state of the anthracene acceptor occurs, as inferred from a combination of time-resolved fluorescence quenching and transient absorption measurements. In toluene at room temperature, the rate constants for photoinduced intraensemble electron-transfer and subsequent back-electron-transfer (charge recombination) are k(CS) = (3.5 +/- 0.03) x 10(10) s(-1) and k(CR) = (1.42 +/- 0.03) x 10(9) s(-1), respectively.

Aniline Compounds↗
PubMed2001

Self-assembled helices from 2,2'-biimidazoles.

2,2'-Biimidazoles were synthesized by palladium(0)-catalyzed coupling of 2-iodoimidazoles bearing an alkyl and an ester group at the 4- and 5-positions, respectively. The products were found to be fluorescent and moderately soluble in organic solvents. Three biimidazoles were subjected to single crystal X-ray diffraction analysis. In all three instances, adjacent molecules were found to be bound together in the solid state by pairs of N-H...N hydrogen bonds, forming twisted ribbon-like columns which resemble double helices. The amount of helical twist observed between neighboring biimidazole subunits in these helices varies with the identity of the alkyl and ester groups; in two cases it is approximately 60 degrees, whereas in the third it is about 90 degrees. Mass spectra of six different biimidazoles display ions with masses corresponding to dimers; this indicates that these compounds retain some affinity for each other in the gas phase. The three most soluble biimidazoles also show mass spectrometric peaks ascribable to trimers and tetramers. The solution-phase aggregation tendencies of these latter three compounds were studied by vapor pressure osmometry. In each case, the apparent molecular weight in 1,2-dichloroethane solution is higher than would be expected for free monomers.

Computer Graphics↗
PubMed2001

Sapphyrins: versatile anion binding agents.

Sapphyrin was the first expanded porphyrin to be reported in the literature and remains among the most extensively studied. Much of the interest in this macrocycle reflects its ability to bind anions, a phenomenon that has been examined in solution and in the solid state by a wide range of experimental techniques. In this Account, we summarize these studies while also outlining strategies that may be used to synthesize sapphyrins.

Anions↗
PubMed2000

Lithiation of meso-octamethylcalix[4]pyrrole: a general route to C-Rim monosubstituted calix[4]pyrroles.

Lithiation and subsequent addition of an electrophile to meso-octamethylcalix[4]pyrrole provides a straightforward synthetic route to new, C-rim monosubstituted calix[4]pyrroles. A variety of electrophiles were used, resulting in calix[4]pyrroles with appended functional groups including carboxyl, ester, iodo, and formyl. This method was optimized to give maximum yields of the monosubstituted derivatives with lowest possible contamination by di- and trisubstituted congeners. Solid-state studies, performed for a number of these derivatives, showed unexpected supramolecular interactions involving both solvents and the monosubstituted calix[4]pyrrole derivatives themselves.

Indicators and Reagents↗
PubMed2000

Electrochemical studies of corrphycenes and metallocorrphycenes.

Corrphycene 3 (Cn) is a structural isomer of porphyrin 1 that was synthesized for the first time 5 years ago. This paper reports on the redox properties of free-base octaethylcorrphycene H2OECn and 16 metal complexes derived therefrom. In CH2Cl2 solution, the free base and the metallo(II) octaethylcorrphycenes, M(II)OECn, typically undergo four distinct one-electron redox steps involving the tetrapyrrolic macrocycle, of which two are reduction steps and two are oxidations. One exception to this general pattern is displayed by the Co(II)OECn complex. In this instance, the first one-electron reduction is metal-centered and produces Co(I)OECn. A comparison of the redox potentials of corrphycenes with those of porphyrins and porphycenes indicates that the first reduction potentials of the free base and of the metallo-octaethylcorrphycenes are between those of the porphycenes-the easiest to reduce molecules in this set of isomeric tetrapyrrolic systems-and those of the porphyrins. The oxidation potentials of corrphycenes and porphyrins are found to be quite similar. On the other hand, porphycenes are oxidized at less positive potentials. The redox gap deltaE1/2 = E1/2Ox1 - E1/2Red1 is equal to 2.15 +/- 0.08 V for the free base corrphycene and the various metallocorrphycenes that were subjected to study. This redox gap is not much different from that observed in porphyrins (deltaE1/2 = 2.25 +/- 0.1 V), whereas if differs significantly from that observed in porphycenes (deltaE1/2 = 1.85 +/- 0.15 V). The sequence of these deltaE1/2 values parallels the lowest energy absorption maxima observed in the UV-vis spectra of these three isomers.

Journal Article↗
PubMed2000

Texaphyrins: new drugs with diverse clinical applications in radiation and photodynamic therapy.

The texaphyrins are quintessential metal-coordinating expanded porphyrins. They constitute a new series of synthetic porphyrin analogues that show promise as drugs for use in a range of medical therapies. Currently, two different water-solubilized lanthanide(III) texaphyrin complexes, namely the gadolinium(III) and lutetium(III) derivatives 1 and 2 (Gd-Tex and Lu-Tex, respectively), are being tested clinically. The first of these, XCYTRIN, is in a pivotal Phase III clinical trial as a potential enhancer of radiation therapy for patients with metastatic cancers to the brain receiving whole brain radiation therapy. The second, in various formulations, is being tested as a photosensitizer for use in: (i) the photodynamic treatment of recurrent breast cancer (LUTRIN; Phase II clinical trials complete), (ii) photoangioplastic reduction of atherosclerosis involving peripheral arteries (ANTRIN; now in Phase II testing), and (iii) light-based treatment of age-related macular degeneration (OPTRIN; currently in Phase I clinical trials), a vision-threatening disease of the retina. Taken in concert, these two metallotexaphyrins provide a powerful new class of experimental drugs whose diverse potential utility is abetted by a combination of well-optimized physical features, favorable tissue biolocalization characteristics, and novel mechanisms of action. Interestingly, these mechanisms may alter conventional wisdom regarding mechanisms of radiation therapy and the pathophysiology of atherosclerosis.

Arteriosclerosis↗
PubMed1999

In vivo animal studies with gadolinium (III) texaphyrin as a radiation enhancer.

PURPOSE: Gadolinium texaphyrin (Gd-Tex, PCI-0120) is an expanded porphyrin that has demonstrated radiation enhancement. In this study, we evaluated the radiation enhancement and biolocalization of Gd-Tex in three animal tumor models. METHODS AND MATERIALS: EMT6, SMT-F, and MCa tumors were established intramuscularly or subcutaneously. Gd-Tex and other metallotexaphyrins were administered prior to single or multiple fractions of radiation. 14C-labeled Gd-Tex was used for biolocalization studies. RESULTS: Gd-Tex, in combination with radiation, produced significant tumor growth delay compared to irradiated control groups in both single and multifraction radiation studies. Gd-Tex radiation enhancement was observed only when the drug was given before, but not after irradiation. Several metallotexaphyrins, identical except for the metal ion, were studied in the EMT6 tumor model including gadolinium (Gd), lutetium (Lu), europium (Eu), yttrium (Y), and cadmium (Cd) texaphyrin complexes. Only Gd-Tex produced radiation enhancement. Biodistribution studies using 14C-labeled Gd-Tex demonstrated drug selectivity and retention in tumors growing intramuscularly compared to uninvolved muscle and plasma. CONCLUSIONS: Gd-Tex produces reproducible radiation enhancement in a variety of in vivo tumor models. This drug's unique radiochemistry, tumor selectivity, and in vivo activity suggests possible mechanisms of action not addressed by in vitro assay methods.

Animals↗
PubMed1998

Anion selectivity of a sapphyrin-modified silica gel HPLC support.

A sapphyrin-modified silica gel support for use in high-performance liquid chromatography was prepared by attaching a sapphyrin monocarboxylic acid to aminopropyl silica gel through an amide bond. The anion retention characteristics of this modified silica gel were tested by exploring the extent to which a specific anion in the mobile phase would act to affect the rate at which AMP was eluted from an HPLC column containing this functionalized stationary phase. In general, it was found that phosphate and arsenate anions were more effective as eluents than carboxylic acids and halides, a result that was interpreted in terms of these former species binding better to sapphyrin (and hence being more effective in terms of displacing AMP) than other anions tested. Support for the contention that phosphate anions will bind to sapphyrin subunits covalently tethered to the silica gel came from solid state 31P NMR spectroscopic analyses. These revealed that the 31P nucleus undergoes a 5 ppm upfield shift, relative to control, when allowed to interact with the sapphyrin-containing support.

Adenosine Monophosphate↗
PubMed1996

Gadolinium(III) texaphyrin: a tumor selective radiation sensitizer that is detectable by MRI.

Gadolinium(III) texaphyrin (Gd-tex2+) is representative of a new class of radiation sensitizers detectable by magnetic resonance imaging (MRI). This porphyrin-like complex has a high electron affinity [E1/2 (red.) approximately = -0.08 V versus normal hydrogen electrode] and forms a long-lived pi-radical cation upon exposure to hydrated electrons, reducing ketyl radicals, or superoxide ions. Consistent with these chemical findings, Gd-tex2+ was found to be an efficient radiation sensitizer in studies carried out with HT29 cells in in vitro as well as in in vivo single and multifraction irradiation studies with a murine mammary carcinoma model. Selective localization of Gd-tex2+ in tumors was confirmed by MRI scanning.

Animals↗
PubMed1996

Phototherapy of cancer and atheromatous plaque with texaphyrins.

Cancer and cardiovascular disease are the leading causes of death in the western world. Photodynamic therapy (PDT) has demonstrated activity in the treatment of superficial cancerous lesions and as an intraoperative adjunct during surgical debulking. Texaphyrins are pure, synthetic water-soluble macrocycles that localize in both cancerous lesions and atheromatous plaque. Lutetium texaphyrin (PCI-0123) is activated by tissue-penetrating far red light (720-760 nm). Patient diagnosis and treatment planning is possible via magnetic resonance imaging (MRI) with the paramagnetic gadolinium texaphyrin (PCI-0120) or via fluorescence imaging using the diamagnetic PCI-0123. In this study it is shown that texaphyrins localize selectively in cancer and atheromatous plaque. PDT with PCI-0123 is found to cause selective photodamage to the diseased tissue. Specifically, PCI-0123 acts to eradicate the SMT-F murine mammary tumors and diet-induced atheromatous plaque in rabbits.

Animals↗
PubMed1996

Lutetium texaphyrin (PCI-0123): a near-infrared, water-soluble photosensitizer.

Lutetium texaphyrin, PCI-0123, is a pure, water-soluble photosensitizer with a large broad absorption band centered at 732 nm. The compound was tested for photodynamic therapy (PDT) effectiveness in a murine mammary cancer model. The texaphyrin macrocycle as illustrated by magnetic resonance imaging and 14C-radiolabeled texaphyrin studies was shown to be tumor selective; a tumor-to-muscle ratio of 10.55 was seen after 5 h. Lutetium texaphyrin, at a drug dose of 20 mumol/kg with irradiation 5 h postinjection at 150 J/cm2 and 150 mW/cm2, had significant efficacy (P < 0.0001) in treating neoplasms of moderate size (40 +/- 14 mm3) and also had significant efficacy (P < 0.0001) in treating larger neoplasms (147 +/- 68 mm3). The PDT efficacy was correlated with the time interval between PCI-0123 administration and light exposure. A 100% cure rate was achieved when photoirradiation took place 3 h postinjection compared to 50% for 5 h using 10 mumol/kg and 150 J/cm2 at 150 mW/cm2. The PDT efficacy was attributable to the selective uptake/retention of the texaphyrin photosensitizer in addition to the depth of light penetration achievable at the 732 nm laser irradiation.

Animals↗