V. A. Ol’shevskaya

Porphyrin photosensitizers solubilized with pluronics in the oxidation of tryptophan

It was shown that water-insoluble porphyrins solubilized with pluronics (ternary block copolymers of ethylene oxide and propylene oxide) efficiently transfer photoexcitation energy to molecular oxygen dissolved in aqueous media to excite it into the singlet state, which is active in oxidizing organic substrates. It was established that the degree of solubilization of porphyrin photosensitizers (PPSs) γ defined as the proportion of PPS molecules passed into the aqueous phase in the dissolution of formed films depends on a single parameter, the initial ratio between the porphyrin and pluronic molar concentrations q. γ = γ(q) dependences for the solubilization of dissimilar water-insoluble porphyrins were analyzed. It was shown that the behavior of all the obtained γ = γ(q) dependences is changed at a characteristic value qmax: when q š qmax, γ ∼ 1, and, when q ≥ ?qmax, the degree of solubilization decreases. It was concluded that solubilized porphyrins are efficient photosensitizers in the oxidation of organic substrates (tryptophan).

The influence of amphiphilic polymers on the photocatalytic activity of water-soluble porphyrin photosensitizers

The influence of amphiphilic polymers polyvinylpyrrolidone, poly(ethylene oxide), poly(vinyl alcohol), and pluronic F127 (propylene oxide-ethylene oxide triblock copolymer) on the catalytic activity of a number of water-soluble metal-free porphyrin photosensitizers was studied in the reaction of tryptophan photooxidation in aqueous solution. The introduction of the specified polymers was found to enhance the activity of carbon-substituted tetrafluorophenylporpyrin, photoditazine, and dimegin. It was ascertained that introduction of polyvinylpyrrolidone had the strongest effect on the increase in the photooxidation process rate; the change in the activity of porphyrins was 30–70%. The introduction of poly(ethylene oxide), poly(vinyl alcohol), and pluronic F127 was shown to enhance the rate of the process by 10–40%. It was concluded that this polymer effect was connected with the dissociation of aggregates, in which form porphyrin molecules were present in aqueous solutions, as indicated by an increase in fluorescence intensity of porphyrins. The introduction of polymers resulted in a bathochromic shift of the fluorescence bands for all porphyrins, which accounted for the formation of complexes of porphyrin sensitizers with the polymers.

Synthesis of boron-containing derivatives of pyropheophorbide a and investigation of their photophysical and biological properties

Proceeding from pyropheophorbide a and 9-hydroxymethyl-m-carborane, 1-hydroxymethyl-o-carborane, and 3-amino-o-carborane new carboranylchlorins were prepared, and their photophysical and biological properties were investigated.

Boronated Derivatives of Chlorin e 6 and Fluoride-Containing Porphyrins as Penetrating Anions: a Study Using Bilayer Lipid Membranes

Boronated derivatives of porphyrins are studied extensively as promising compounds for boron-neutron capture therapy and photodynamic therapy. Understanding of the mechanism of their permeation across cell membranes is a key step in screening for the most efficient compounds. In the present work, we studied the ability of boronated derivatives of chlorin e6 and porphyrins, which are mono-, di-, and tetra-anions, to permeate through planar bilayer lipid membranes (BLM). The translocation rate constants through the hydrophobic part of the lipid bilayer were estimated for monocarborane and its conjugate with chlorin e6 by the method of electrical current relaxation. They were similar, 6.6 and 6.8 sec−1, respectively. Conjugates of porphyrins carrying two and four carborane groups were shown to permeate efficiently through a BLM although they carry two charges and four charges, respectively. The rate of permeation of the tetraanion estimated by the BLM current had superlinear dependence on the BLM voltage. Because the resting potential of most mammalian cells is negative inside, it can be concluded that the presence of negatively-charged boronated groups in compounds should hinder the accumulation of the porphyrins in cells.

Synthesis and antitumor activity of novel tetrakis[4-(closo-carboranylthio)tetrafluorophenyl]porphyrins

Novel neutral and anionic fluorinated carboranylporphyrins for boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) were synthesized by the reaction of 5,10,15,20-pentafluorophenylporphyrin and its copper(II), zinc(II), and palladium(II) complexes with closo-mercaptocarboranes and cesium 1-mercapto-1-carba-closo-dodecaborate. Preliminary evaluation of biological activity reveals that anionic carboranylporphyrins are promising agents for BNCT and PDT.

Synthesis of bis(dialkylaminomethyl)-o- andm-carboranes and study of these compounds as potential preparations for boron neutron capture therapy

A very important problem tbr neutron capture therapy (NCT) of patients with malignant neoplasms based on the I~ or, q,)7Li reaction (B-NCT) consists in creating organoboron compounds capable of selectively accumulating in the target tumor tissues. The results of calculations indicate that, provided the thermal neutron fluence reaches an upper limit of 1013 n/cm 2, the absolute concentration of boron10 nuclei in the tumor must reach (assuming their homogeneous distribution) 109 atoms per cell or 20 35(40) lag/g. On the other hand, in order to eliminate radiation damage of healthy tissues and blood vessels in the irradiated volume, the amount of boron-10 in these regions during the neutron irradiation must not exceed one-third of that in the tumor [I]. These relationships must hold over the whole time of the B-NCT treatment (lasting for at least several hours). From the standpoint of solving this task, of special interest are compounds belonging to the carborane group. A large amount of boron (ten atoms) in their polyhedral molecules makes these compounds a promising base for the development of B-NCT preparations. Moreover, methods for the incorporation of icosahedral C2BioHl: carborane molecules into various organic and biochemical substrates are already well developed. Numerous investigations in this direction were devoted predominantly to o-carborane derivatives [2]. In recent years, however, there was a considerable shift in the interest of researchers toward m-carborane derivatives possessing increased stability with respect to the action of various bases. In this study, we have synthesized two water-soluble amino derivatives of oand m-carboranes, 1,2-bis(dimethyl-

Complexes of antiparallel telomeric G-quadruplex d(TTAGGG)4 with carboxymethyl tetracationic porphyrins

Porphyrins are a chemical class that is widely used in drug design. Cationic porphyrins may bind to DNA guanine quadruplexes. We report the parameters of the binding of 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium) porphyrin (P1) and 5,10,15,20-tetrakis(N-etoxycarbonylmethyl-4-pyridinium) porphyrin (P2) to antiparallel telomeric G-quadruplex formed by d(TTAGGG)4 sequence (TelQ). The binding constants (Ki) and the number of binding sites (Nj) were determined from absorption isotherms generated from the absorption spectra of complexes of P1 and P2 with TelQ. Compound P1 demonstrated a high affinity to TelQ (Ki = (40 ± 6) × 106 M−1, N1 = 1; K2 = (5.4 ± 0.4) × 106 M−1, N2 = 2). In contrast, the binding constants of P2-TelQ complexes (K1 = (3.1 ± 0.2) × 106 M−1, N1 = 1; K2 = (1.2 ± 0.2) × 106 M−1, N2 = 2) were one order of magnitude smaller than the corresponding values for P2-TelQ complexes. Measurements of the quantum yield and fluorescence lifetime of the drug’s TelQ complexes revealed two types of binding sites for P1 and P2 on the quadruplex oligonucleotide. We concluded that strong complexes can result from the interaction of the porphyrins with TTA loops whereas the weaker complexes are formed with G-quartets. The altered TelQ conformation detected by the circular dichroism spectra of P1-TelQ complexes can be explained by the disruption of the G-quartet. We conclude that peripheral carboxy groups contribute to the high affinity of P1 for the antiparallel telomeric G-quadruplex.

Synthesis of boronated derivatives of pheophorbide a

294 Photodynamic therapy (PDT) [1] and boron neutron capture therapy (BNCT) [2] are promising clinical approaches enabling a local effect on a tumor with little if any damage to the healthy tissue around it. Both methods are based on the selective accumulation of photoand radiosensitizer in cancer cells and in situ production of high-energy particles upon activation of the sensitizer by light of a definite wavelength (PDT, ) or thermal neutrons (BNCT, 4 He 2+ and 7 Li 3+ ). The particles produced in a tumor have short path lengths comparable with the cell size, which allows them to locally destroy tumor cells (apoptosis, necrosis) leaving healthy tissue intact [3]. Furthermore, PDT used for the treatment of O2 – Synthesis of Boronated Derivatives of Pheophorbide a

Synthesis of carborane conjugates based on the maleimide derivative of 5,10,15,20-tetraphenylporphyrin

165 Carboranylporphyrins are biologically active com pounds interesting as photo/radiosensitizers for binary antitumor strategies, such as photodynamic therapy (PDT) and boron neutron capture therapy (BNCT). Photodynamic therapy, a non surgical method of treatment of oncological diseases that has come to stay in clinical practice in recent years, employs the capa bility of a photosensitizer compound to produce on illumination active oxygen species, such as singlet oxygen O2, free radicals, e.g., OH, •HO2, and , as well as H2O2, which can damage proteins, DNA, membranes, and other cell components [1, 2]. Boron neutron capture therapy used in the treatment of brain, liver, and skin tumors is based on the nuclear reaction of nonradioactive isotope 10B with thermal

Synthesis and antitumor properties of carborane conjugates of 5-(4-aminophenyl)-10,15,20-triphenylporphyrin

91 Porphyrins and their derivatives represent an impor tant class of macroheterocycles with unique properties. The practical use of these compounds embraces impor tant fields such as photosynthesis, non linear optics, catalysis, and nanomaterials [1–7]. Porphyrins and other tetrapyrrole macrocycles are intensively used for the photodynamic therapy (PDT) of cancer and other diseases. This efficient therapy is based on the ability of porphyrins to be selectively accumulated in the tumor cells and generate active oxygen species (О2, НO –, HO . , and O . ) upon excitation with monochromatic light, which results in the tumor decay.