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D Dolphin

Publications and source records attributed to D Dolphin.

At least 37 records · Page 2Linked to original sources
PubMed1989

Biomimetic chemistry of hemeproteins.

Hemeproteins play important physiological roles for an oxygen metabolism in living organisms. Their functions are divided to three main groups, i) hemoglobins, myoglobins and the cytochromes which function by transporting and storing dioxygen and electrons; ii) catalase and peroxidases which are activated by hydrogen peroxide, iii) cytochrome oxidase and cytochrome P450 both of which bind dioxygen and use the dioxygen as an electron sink or by partially reducting the dioxygen to make a powerful oxidizing agent. The hemeproteins included to group ii) have been established to produce a reaction intermediate, oxo-ferry (Fe(IV] pi-cation radical, during the catalytic cycle. Recent model studies to mimic cytochrome P450 catalyzed-reaction have shown that the intermediate retains an activated oxygen and functions as a powerful oxidizing agent in the monoxygenase reaction. In this article, the properties of the intermediate and the role in cytochrome P450 monoxygenase reaction is summarized.

Chemical Phenomena↗
PubMed1988

The excited states of covalently linked dimeric porphyrins. I: The excited singlet states.

The ground state absorbance and emission properties of a series of covalently linked biporphyrins were studied, in both their neutral and dicationic forms. The fluorescence quantum yields determined are comparable in value with that obtained from haematoporphyrin IX. Soret band splitting is observed for porphyrin rings separated by a hydrocarbon chain containing 0-3 carbons joined at the beta,beta' ring positions. The biporphyrin linked directly at the meso position shows considerable steric hindrance and behaves like two independent chromophores.

Chemical Phenomena↗
PubMed1987

Preliminary studies on a more effective phototoxic agent than hematoporphyrin.

Phototoxicity of benzoporphyrin derivative (BPD) has been tested in vitro and compared with that of hematoporphyrin (HP). After 1-hour activation with visible light, BPD was 10 times more cytotoxic than HP toward human adherent cell lines: A549 lung cancer, Calu-1 lung carcinoma, and CCD-19Lu normal lung, killing 100% of cells at the concentration of 70 ng/ml. Under the same conditions, BPD was 10-70 times more cytotoxic than HP toward nonadherent cells and cell lines. Tested were human leukemia cell lines HL60, K562, and KG1, normal human lymphocytes, and mouse mastocytoma cell line P815. The concentrations required to kill 100% of cells varied between 10 and 500 ng BPD/ml and between 0.2 and 10 micrograms HP/ml. The difference between the nonadherent cell lines in respect to their sensitivity to phototoxicity of both BPD and HP seemed to be related to the cell sizes, with the smallest cells being the most vulnerable. The most attractive characteristic of BPD in addition to its powerful phototoxicity is its maximum absorption around 700 nm, which is in the range of wavelengths penetrating tissues the best. This characteristic alone could make BPD a drug of choice in cancer photodynamic therapy when the safety of its use is ensured. Preliminary tests in vivo have shown that DBA/2J mice can tolerate a single ip injection of 20-60 micrograms BPD as well as the same dose of HP. The biodistribution and toxicity studies of BPD are under way in our laboratory.

Animals↗
PubMed1985

Cytochrome P450: substrate and prosthetic-group free radicals generated during the enzymatic cycle.

During the enzymatic cycle of the cytochromes P450, dioxygen binds to the ferrous haemprotein when the resting ferric haemprotein has undergone a one-electron oxidation after substrate binding. A further one-electron reduction generates an intermediate that is isoelectronic with a peroxide dianion coordinated to a ferric iron. Heterolytic cleavage of the omicron--omicron bond generates water and a species which is formally an oxene (oxygen atom) coordinated by iron(III). However, on the basis of model reactions and by analogy to the catalases and peroxidases, this active oxidizing intermediate is formulated as an oxo-FeIV porphyrin pi-cation radical. The radical is stabilized by delocalization on the porphyrin macrocycle and the high oxidation state is achieved by oxidizing both the metal and the porphyrin ring of the haemprotein. Hydrogen atom abstraction from a saturated hydrocarbon substrate generates a substrate free radical, constrained by the protein binding site, and the equivalent of a hydroxyl radical bound to iron(III). Coupling of the 'hydroxy' and substrate radicals generates hydroxylated product and resting protein. For olefins an initial electron transfer to oxidized haemprotein gives a substrate cation radical. Further reaction of this radical can give the epoxide, the principal product; an aldehyde or ketone by rearrangement; or an alkylated haemprotein resulting in suicide inhibition.

Catalase↗
PubMed1984

An internal standard for porphyrin analysis.

The routine clinical analysis of the porphyrin precursors of heme requires an internal standard to determine the efficiency of the analytical procedure used. 2-Vinyl-4-hydroxymethyldeuteroporphyrin IX has been prepared as an internal standard. Its application to porphyrin analysis has been demonstrated using high-performance liquid chromatographic resolution of the uro- to protoporphyrins in normal and porphyric urine.

Chromatography, High Pressure Liquid↗
PubMed1983

Potential use of radiolabelled porphyrins for tumor scanning.

Fe-TMPI, Fe-TCP and protohemins showed high initial uptake using tissue culture techniques with mouse tumor cells (P815). However, the tumor uptake in the in vivo model was poor. Of the radionuclides investigated, iron labelled to TMPI demonstrated the best uptake by tumor in vitro. As has been previously demonstrated, the unnatural meso-arylporphyrin derivatives showed better uptake than did naturally occurring porphyrins and their derivatives.

Animals↗
PubMed1980

Resonance Raman evidence for cleavage of the Fe-N epsilon(His-F8) bond in the alpha subunit of the T-structure nitrosylhemoglobin.

Resonance Raman spectra are observed for hybrid nitrosylhemoglobins (NO-Hb) reconstituted from normal and meso-deuterated hemes and also for penta- and hexa-coordinated NO-heme complexes. Upon meso deuteration of both hemes of the alpha and beta subunits [alpha(D)2NO beta(D)2NO], the Raman lines of stripped NO-Hb at 1636 (dp), 1584 (ap), and 1502 (p) cm-1 are shifted by -10, -20, and -7 cm-1, respectively, and those at 1306 (ap) and 1228 (dp) cm-1 disappear. The spectral changes caused by meso deuteration are in good agreement with those observed previously for (octaethyl-porphyrinato)nickel(II), for which the vibrational assignments of resonance Raman lines have been established. Accordingly, the 1636-, 1584-, 1502-, 1306-, and 1228-cm-1 lines of NO-Hb are assigned to nu 10, nu 19, nu 3, nu 21, and nu 13, respectively. Upon conversion from the R to the T structure, both nu 19 and nu 3 are shifted to higher frequencies by 4 cm-1 and nu 10 is split into two lines at 1645 and 1637 cm-1. The 1645-cm-1 line remains unshifted after meso deuteration of the beta heme [alpha(H)2NO beta-(D)2NO], and, conversely, the 1637-cm-1 line remains unshifted after meso deuteration of the alpha heme [alpha(D)2NO beta(H)2NO]. On the basis of the Raman spectra of the model NO-heme complexes, the 1645- and 1637-cm-1 lines are assigned to the penta- and hexacoordinated NO-heme complexes. Consequently, we conclude that the Fe-N epsilon(His-F8) of the alpha subunit within NO-Hb is disrupted in the T structure, while the NO-heme of the beta subunit adopts the hexacoordinated structures, in good agreement with our previous electron paramagnetic resonance work. The Raman spectra of the isolated alpha NO and beta NO chains are appreciably different. The Raman lines of the isolated alpha NO chain at 1606 (p), 1587 (ap), and 1504 (p) cm-1 are shifted by -6, +5, and +4 cm-1 when it is incorporated into the T-structure tetramer. In contrast, all the Raman lines of the isolated beta NO chain are not shifted in the T-structure tetramer.

Chemical Phenomena↗
PubMed1979

Preparation of ruthenium(II) and ruthenium(III) myoglobin and the reaction of dioxygen, and carbon monoxide, with ruthenium(II) myoglobin.

Ruthenium myoglobins have been prepared by the reconstitution of horse heart apomyoglobin with either ruthenium(II) or ruthenium(III) mesoporphyrin IX (MpIX) derivatives. The ruthenium(II) and -(III) myo globins (RuMb and RuMb+, respectively) contain one ruthenium porphyrin/heme binding site; the species are readily interconverted using dithionite for reduction and bromine for oxidation. RuMb binds carbon monoxide to give the known carbonyl complex. Reversible oxygenation occurs readily with protein-free RuII(MpIX) species in dimethylformamide, but RuMb in phosphate buffer is irreversibly oxidized by dioxygen to give RuMb+ via an outer sphere electron transfer mechanism.

Animals↗
PubMed1978

Copper coproporphyrin excretion in familial coproporphyria.

Analysis of stool specimens from a patient with familial coproporphyria by high-performance liquid chromatography revealed that 112 microgram per gram of dry feces (14% of the total porphyrin present) was copper coproporphyrin. Examination of stool specimens from other patients with this disease confirmed the presence of significant amounts of both copper coproporphyrin and coproporphyrin. Further investigation showed that the copper coproporphyrin was probably formed by a nonenzymic incorporation of copper by the coproporphyrin in either the bile or feces.

Adolescent↗