Clifford C. Leznoff

Recent studies in phthalocyanine chemistry

Abstract : This paper summarizes research in phthalocyanine chemistry carried out in our laboratories during the last few years. Included herein are synthesis of binuclear and polynuclear phthalocyanines, oxygen reduction studies using phthalocyanine monolayers on graphite electrodes, emission characteristics of mono- and polynuclear phthalocyanines, electrochemical and spectro-electrochemical properties, aggregation behaviour, and consideration of the electronic coupling present in the polynuclear species. The paper finishes with a survey of recent important contributions from other laboratories.

Synthesis, electrochemical and spectroelectrochemical studies of metal-free 2,9,16,23-tetraferrocenylphthalocyanine

Abstract Cyclic voltammetric, differential pulse voltammetric and spectroelectrochemical methods have been used to study the newly synthesized metal-free 2,9,16,23-tetraferrocenylphthalocyanine in dichloroethane. Two reversible reduction peaks are obtained, corresponding to electrode reactions of the phthalocyanine ring. The multiple ferrocenyl redox centers are oxidized at one potential. The electronic spectra are reported for this species in different oxidation states.

Effect of 2-methylcitrate on citrate metabolism: implications for the management of patients with propionic acidemia and methylmalonic aciduria.

Extract: 2-Methylcitrate was tested in vitro on enzymes which interact with citrate and isocitrate. It was found to inhibit citrate synthase, aconitase, the NAD+- and NADP+-linked isocitrate dehydrogenase. This inhibition was competitive in nature except in the case of aconitase, and the Ki for all the enzymes was in the range of 1.5-7.6 mM. Phosphofructokinase was also inhibited by 2-methylcitrate with 50% inhibition achieved at 1 mM. ATP-citrate lyase and acetyl-CoA carboxylase were not inhibited by this compound. 2-Methylcitrate was not a substrate for ATP-citrate lyase. Acetyl-CoA carboxylase was activated by 2-methylcitrate with a Ka of 2.8 mM. The apparent Km (3.3 mM) for 2-methylcitrate for the mitochondrial citrate transporter was about 10-fold higher than the apparent Km (0.26 mM) for citrate. The tricarboxylate carrier can also be inhibited by low concentrations (0.2 mM) of 2-methylcitrate when the concentration of citrate is close to the apparent Km. Accumulation of 2-methylcitrate inside the mitochondrion, therefore, might lead to inhibition of enzymes in the citric acid cycle and thereby contribute to the ketogenesis and hypoglycemia seen under these conditions.Speculation: Treatment of patients with propionic aciduria and methylmalonic aciduria with alkali therapy would be advantageous with respect to the acidemia but also would cause a more rapid exit of 2-methylcitrate from the mitochondrion. Alkalinization with sodium citrate might be even more beneficial if this citrate could enter the liver and allow more rapid removal of 2-methylcitrate and methylmalonate from liver mitochondria since increased cytosolic levels of these intermediates would facilitate more rapid diffusion to the extracellular space and eventual excretion in the urine. This therapy does not exclude the low protein diet and for the vitamin-responsive form of methylmalonic aciduria, B12 treatment.

THE EFFECT OF SUBSTITUENTS ON PHTHALOCYANINE PHOTOCYTOTOXICITY

Phthalocyanine (Pc) dyes are a class of photosensitizers that are being considered for use in the photodynamic therapy of cancer. A final choice for the most useful drug demands phototoxicity screening of various structurally related Pc dyes, such as those with different substituents at the peripheral benzene rings. Using the colony forming ability of Chinese hamster cells as an endpoint, the photobiological activity for ZnPc was found to be the highest for the unsubstituted compound, followed in decreasing order by the 2,9,16,23‐tetrahydroxy‐, 2,9,16,23‐tetrasulfonated‐, and 2,9,16,23‐tetraneopentoxy‐Pc derivatives. This effect could be correlated with the uptake rate of the respective Pc derivatives by the cells, but it is unrelated to the apparent lipophilicity of these compounds, or, alternatively, to their ability to photogenerate singlet oxygen. The first synthesis of a metal‐free tetrahydroxy Pc is described.

SYNTHESIS AND PHOTOCYTOTOXICITY OF SOME NEW SUBSTITUTED PHTHALOCYANINES

Abstract Some new, ring‐substituted phthalocyanines have been synthesized and underwent preliminary testing for photodynamic activity using the colony forming ability of Chinese hamster cells in culture as an endpoint. Using 4‐(3‐N, N‐diethylaminopropyl)phthalonitrile as a precursor, the previously unknown metal‐free 2,9,16,23‐tetra‐(3‐N, N‐diethylaminopropyl)phthalocyanine was prepared and converted to its zinc (II) and its cationic water‐soluble 2,9,16,23‐tetramethylammonium zinc (II) iodide derivatives. Other new phthalocyanine derivatives tested, include a 2,9,16,23‐tetra(2‐hydroxymethyl‐2‐methyIbutoxy)phthalocyaninato zinc (II) and 2,3,9,10,16,17,23,24‐octahydroxyphthalocyaninato zinc (II) derivatives. Boron tribromide cleavage of the newly prepared and fully characterized 2,3,9,10,16,17,23,24‐octamethoxyphthalocyanine gave the unstable metal‐free octahydroxyphthalocy‐anine, which could only be characterized by ultraviolet‐visible, NMR and IR spectroscopy.

Electrochemistry and Spectroelectrochemistry of Polynuclear Zinc Phthalocyanines: Formation of Mixed Valence Cation Radical Species

The electrochemistry and spectroelectrochemistry of mononuclear, binuclear and tetranuclear zinc neopentoxy-substituted phthalocyanines are presented. The binuclear and tetranuclear species show two oxidation waves to the radical cation indicating the existence of stable mixed-valence, half-oxidized species. The electronic spectra of the half− and fully-oxidized species are presented and discussed. Nernstian analysis shows that pairs of phthalocyanine rings are oxidized simultaneously in the tetranuclear species, via a one-electron oxidation pathway.

Synthesis and NMR Studies of a Single Isomer of an Alkynyl Substituted Binuclear Phthalocyanine

By a mixed condensation of 1,3-bis(3″,4″-dicyanophenoxy)-2-ethyl-2-methylpropane with a large amount of 4,5-bis(3,3-dimethyl-1-butynyl)phthalonitrile, 1,3-bis-2″-(9″,10″,16″,17″,23″,24″-hexakis(3″,3″-dimethyl-1″-butynyl)phthalocyaninoxyl)-2-ethyl-2-methylpropane, was synthesized as a binuclear phthalocyanine having a single isomer. NMR studies at various temperatures and concentrations suggested that the interactions between the phthalocyanine macrocycles were dominated by intermolecular aggregation at lower temperatures or high concentrations whereas intramolecular aggregation was predominant at higher temperatures or lower concentrations.

Phthalocyanine formation using metals in primary alcohols at room temperature

Lithium metal added to a solution of 4-neopentoxyphthalonitrile in 1-octanol or other long-chain primary alcohols at room temperature resulted in phthalocyanine formation at a reasonable rate in good yield, while preformed lithium 1-octanolate under the same conditions gave 2,9,16,23-tetraneopentoxyphthalocyanine, but in lower yield at a slower rate. The use of lower-molecular-weight alcohols slowly gave a phthalocyanine in lower yields. Reverse micelle formation when using long-chain alcohols is proposed as a possibility for enhanced phthalocyanine formation at room temperature. 2,9,16,23-Tetrasubstituted phthalocyanines and metallated phthalocyanines were prepared at room temperature from 4-neopentoxyphthalonitrile, 4-bis(4-methoxyphenyl)methoxyphthalonitrile, 4-[1-(4-ethoxy-3-methoxyphenyl)-1-phenyl]methoxyphthalonitrile and phthalonitrile using lithium 1-octanolate in 1-octanol or by the addition, to a solution of the phthalonitrile in ethanol, of calcium turnings or, to a solution of the phthalonitri...

Syntheses of Octaalkynylphthalocyanines from Halophthalonitriles

Coupling of 4,5-diiodophthalonitrile with tert-butyldimethylsilylacetylene and a palladium catalyst gave 4,5-bis(tert-butyldimethylsilylethynyl)phthalonitrile. Cleavage of the silyl moiety with tetrabutylammonium fluoride gave 4,5-diethynylphthalonitrile, while condensation in 2-N,N-dimethylaminoethanol without or with Zn(OAc)2 gave metal-free 2,3,8,9,16,17,23,24-octakis(tert-butyldimethylsilylethynyl)phthalocyanine or its zinc derivative. Cleavage of the silyl groups of the zinc derivative gave an insoluble product whose 1H NMR spectrum was indicative of 2,3,9,10,16,17,23,24-octaethynylphthalocyaninato zinc(II). Bromination of phthalonitrile with N,N-dibromoisocyanuric acid gave a separable mixture of 3,6-, 3,4- and 4,5-dibromophthalonitrile along with the monobromophthalonitriles. Coupling of 3,4-dibromophalonitrile with tert-butylacetylene gave 3,4-bis(tert-butylethynyl)phthalonitrile, which on condensation with lithium 1-pentanolate gave 1,2,8,9,15,16,22,23-octakis(3,3-dimethyl-1-butynyl)phthalocyanin...

A Stereoselective Synthesis of a Cis, Cis Conjugated Dienol, a Candidate Pheromone

Abstract There has been much interest recently focussed on the synthesis of geometrically pure conjugated diene alcohols, aldehydes and esters useful as sex pheromones and candidate sex attractants.1,2 A recent communication3 on the synthesis of all four geometrical isomers of some conjugated dienols by four different Wittig reactions prompts us to report our results on the synthesis of a cis, cis conjugated dienol, as the reported synthesis of this type of isomer yielded product of low geometrical purity.3 We describe below our stereo-selective synthesis of a cis, cis conjugated dienol