Pressure-dependent Fourier transform infrared spectroscopy of a poly (ester urethane)

The effects of hydrostatic pressure upon (1) a segmented poly (ester urethane), (2) a hydrolytically degraded sample of the same polymer, and (3) models for the polyurethane and polyester segments in this polymer have been studied by Fourier transform infrared spectroscopy using high-pressure diamond anvil cells (DACs). The pressure responses of the vibrational frequencies of specific functional groups of the poly (ester urethane) in the 0-100-kbar range are compared with data for individual segment models and the partially degraded sample. The results indicated that the polymer is highly stable in this pressure regime, with no measurable degradation or phase changes. Differences in the pressure dependency of specific infrared bands between the poly (ester urethane) sample and the partially degraded sample are slight and consistent with changes in hydrogen-bonding interactions and shorter chain lengths in the degraded sample.     

The peripheral benzodiazepine receptor in photodynamic therapy with the phthalocyanine photosensitizer Pc 4

The peripheral benzodiazepine receptor (PBR) is an 18 kDa protein of the outer mitochondrial membrane that interacts with the voltage-dependent anion channel and may participate in formation of the permeability transition pore. The physiological role of PBR is reflected in the high-affinity binding of endogenous ligands that are metabolites of both cholesterol and heme. Certain porphyrin precursors of heme can be photosensitizers for photodynamic therapy (PDT), which depends on visible light activation of porphyrin-related macrocycles. Because the apparent binding affinity of a series of porphyrin analogs for PBR paralleled their ability to photoinactivate cells, PBR has been proposed as the molecular target for porphyrin-derived photocytotoxicity. The phthalocyanine (Pc) photosensitizer Pc 4 accumulates in mitochondria and structurally resembles porphyrins. Therefore, we tested the relevance of PBR binding on Pc 4-PDT. Binding affinity was measured by competition with 3H-PK11195, a high-affinity ligand of PBR, for binding to rat kidney mitochondria (RKM) or intact Chinese hamster ovary (CHO) cells. To assess the binding of the Pc directly, we synthesized 14C-labeled Pc 4 and found that whereas Pc 4 was a competitive inhibitor of 3H-PK11195 binding to the PBR, PK11195 did not inhibit the binding of 14C-Pc 4 to RKM. Further, 14C-Pc 4 binding to RKM showed no evidence of saturation up to 10 microM. Finally, when Pc 4-loaded CHO cells were exposed to activating red light, apoptosis was induced; Pc 4-PDT was less effective in causing apoptosis in a companion cell line overexpressing the antiapoptotic protein Bcl-2. For both cell lines, PK11195 inhibited PDT-induced apoptosis; however, the inhibition was transient and did not extend to overall cell death, as determined by clonogenic assay. The results demonstrate (1) the presence of low-affinity binding sites for Pc 4 on PBR; (2) the presence of multiple binding sites for Pc 4 in RKM and CHO cells other than those that influence PK11195 binding; and (3) the ability of high supersaturating levels of PK11195 to transiently inhibit apoptosis initiated by Pc 4-PDT, with less influence on overall cell killing. We conclude that the binding of Pc 4 to PBR is less relevant to the photocytotoxicity of Pc 4-PDT than are other mitochondrial events, such as photodamage to Bcl-2 and that the observed inhibition of Pc 4-PDT-induced apoptosis by PK11195 likely occurs through a mechanism independent of PBR.     

Thermal fragmentation of the guanidinato aluminum amide precursor [Me2NC(NPr)2]Al(NMe2)2: An investigation of reactive species by matrix-isolation FTIR spectroscopy and time-of-flight mass spectrometry

The gas-phase thermolysis of the guanidinato aluminum amide precursor [Me₂NC(NⁱPr)₂]Al(NMe₂)₂ (1) in the oven temperature range of ambient temperatures to 600 °C has been investigated with matrix-isolation FTIR spectroscopy and time-of-flight mass spectrometry (argon as carrier gas). Precursor 1 fragments above 300 °C to form iPrCNCiPr (2) and monomeric Al(NMe₂)₃ (3m). Independent thermolysis series with 2 and the aluminum amide dimer 3d, [Al(NMe₂)₃]₂, were conducted and been used to interpret the results of the fragmentation of precursor 1. Compound 3m was present in the thermolysis range of 350–450 °C and has been identified for the first time. Through a comparison of measured FTIR spectra with the calculated spectrum of 3m (D₃ point group symmetry; B3LYP/6-31G(d) level of theory) all expected IR bands were found and could be assigned to normal modes. At thermolysis temperatures of ?500 °C signals indicative for H₂CNCH₃ (4) were found, showing that 3m fragments further at higher temperature. The thermolysis product 2 (iPrCNCiPr) withstands the higher thermolysis temperatures. From our study one can conclude that precursor 1 cleanly delivers the monomeric aluminum alane 3m, which then acts as the reactive material forming species.     

Effect of the functionalization of the axial phthalocyanine ligands on the energy transfer in QD-based donor-acceptor pairs.

This study examines the electronic coupling between quantum dots (QDs) and molecules on their surfaces as a function of the modality of their interaction. As a probe, the energy transfer (ET) between CdSe QDs and phthalocyanines (Pcs) was monitored and evaluated with regard to the functionalization of the axial phthalocyanine ligand, bulkiness of the functional group bridging the QD donor and Pc acceptor, and the number of the functionalized axial ligands. New silicon PCs and their conjugates with CdSe QDs were synthesized. The ET efficiency and kinetics were studied by steady state and femtosecond time-resolved absorption spectroscopy. We observed a decrease in ET efficiency with the increase in functional group bulkiness, which could be explained by increasing steric hindrance between the ET pair. In addition, a higher ET efficiency was observed for amino and thiol functionalized Pcs compared to Pcs without functional group on the axial alkyl chain.     

NEW PHTHALOCYANINE PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY

Six new aluminum and silicon phthalocyanines have been synthesized and their photocytotoxicity toward V79 cells has been studied. The compounds that have been prepared are: AIPcOSi(CH₃)₂(CH₂),N(CH₃)₂, I; AIPcOSi(CH₃)₂(CH₂)₃N(CH₃)₃⁺I^?, II; CH₃SiPcOSi(CH₃)₂(CH₂)₃N(CH₃)₂, III; HOSiPcOSi(CH₃)₂(CH₂)₃N(CH₃)₂, IV; HOSiPcOSi(CH₃)₂(CH₂)₃)₃(CH₃)₃⁺I^?, V; and SiPc[OSi(CH₃)₂(CH₂)₃N(CH₃)₃⁺I^?]₂, VI. Relative growth delay values for compounds I-VI and relative cytotoxicity values for compounds I, II, IV, V and VI have been determined. Compounds I and II have been shown to be comparable in photocytotoxicity to what is presumed to be AIPcOH.xH₂O, and compound IV has been shown to have greater activity. The classes of compounds to which these six compounds belong appear to have potential for photodynamic therapy.     

Treatment of Malignant Melanoma by High-Peak-Power 1064 nm Irradiation Followed by Photodynamic Therapy

Irradiation of B16 pigmented melanoma subcutaneously transplanted in C57 mice with a single 650 mj pulse (10 ns) of 1064 nm light from a Q-switched Nd: YAG laser caused instantaneous bleaching of the pigmented tissue. Visual and histological examination of the resulting gray-colored tumor revealed the breakdown of melanosomes with no detectable alteration of the normal and tumor-overlying skin. Histological examination of the irradiated tumor showed some degree of vascular damage; the depth of the photodamage was not affected by the successive delivery of three consecutive light pulses. The bleached tumor grew at a modestly slower rate but the high-peak-power (HPP) laser treatment did not affect the tumor concentration of a photodynamic sensitizer Si(IV)-naphthalocyanine (isoBO-SiNc) intravenously injected 24 h before Nd : YAG irradiation. Treatment of the B16 pigmented melanoma by photodynamic therapy (PDT: 1 mg/kg isoBO-SiNc, 300 mW/cm², 520 J/cm²) from a 774 nm diode laser immediately after the 1064 nm irradiation resulted in a 16 day delay of tumor regrowth, which was markedly longer than the delay (ca 6 days) obtained after PDT under identical conditions without the preirradia-tion. Thus, pretreatment of pigmented tumors with HPP 1064 nm light appears to enhance their susceptibility to conventional PDT. The tumor response was further enhanced by repeating the combined HPP/PDT treatment at an interval of 10 days (regrowth delay: 27 days), as well as by applying hyperthermia immediately after HPP/PDT (regrowth delay: ca 34 days).     

Deep penetration of a PDT drug into tumors by noncovalent drug-gold nanoparticle conjugates

Efficient drug delivery to tumors is of ever-increasing importance. Single-visit diagnosis and treatment sessions are the goal of future theranostics. In this work, a noncovalent PDT cancer drug-gold nanoparticle (Au NP) conjugate system performed a rapid drug release and deep penetration of the drug into tumors within hours. The drug delivery mechanism of the PDT drug through Au NPs into tumors by passive accumulation was investigated via fluorescence imaging, elemental analysis, and histological staining. The pharmacokinetics of the conjugates over a 7-day test period showed rapid drug excretion, as monitored via the fluorescence of the drug in urine. Moreover, the biodistribution of Au NPs in this study period indicated clearance of the NPs from the mice. This study suggests that noncovalent delivery via Au NPs provides an attractive approach for cancer drugs to penetrate deep into the center of tumors.     

Oxidative coupling of porphyrins using copper(II) salts

A method for radical coupling of porphyrins using copper(II) salts as one-electron oxidants was developed. A Zn(II)-porphyrin bearing an aminophenyl group yielded porphyrin oligomers, and two tri-arylporphyrins were oxidized to form doubly and triply linked dimers. Bromination of doubly linked dimers gave macrocycles with twisted skeletons.