Novel Chlorin with a HYNIC: Synthesis, Tc-Radiolabeling, and Initial Preclinical Evaluation.

The use of radiopharmaceuticals for diagnostics in oncology allows for the detection of the disease at an early stage. Among diagnostic radionuclides, Tc is a promising isotope that has been used to create several drugs for clinical use. One of the most effective Tc chelators is 6-hydrazinylnicotinic acid (HYNIC), which, when combined with various vector molecules, can be used for targeted delivery of radionuclides to tumor tissues.

Charge-compensated -carborane derivatives in the synthesis of iron(II) bis(dicarbollide) complexes.

A series of stable iron(II) bis(dicarbollide) derivatives [8,8'-(RNHC(Et)HN)-3,3'-Fe(1,2-CBH)] (R = Pr, R = Ph, (CH)OH, (CH)OH, (CH)NMe) was prepared starting from FeCl or [FeCl(dppe)] and the corresponding -carboranyl amidines [10-RNHC(Et)HN-7,8-CBH]. In a similar way, the reactions of the oxonium derivatives of -carborane with FeCl in tetrahydrofuran in the presence of -BuOK lead to the corresponding stable oxonium derivatives iron(II) bis(dicarbollide) [8,8'-(RR'O)-3,3'-Fe(1,2-CBH)] (RR' = (CH), (CH)O(CH), (CH); R = R' = Et), which can be alternatively prepared by the reaction of the parent iron(II) bis(dicarbollide) with tetrahydrofuran or 1,4-dioxane in the presence of MeSO. The cyclic voltammetry studies of the synthesized iron(II) bis(dicarbollide) derivatives revealed that the introduction of amidinium and oxonium substituents leads to a significant increase in the Fe/Fe redox potential relative to the parent iron(II) bis(dicarbollide).

Nickel(II) and Palladium(II) Complexes with η:κ()-Coordinated Dicarbollide Ligands Containing Pendant Pyridine Group.

A series of - and -substituted -carborane derivatives with a pendant pyridyl group was prepared. The synthesized compounds were used as ligands in the complexation reactions with bis(triphenylphosphine)nickel(II) and palladium(II) chlorides to give six new metallacomplexes with unusual η:κ()-coordination of the metal center. The single crystal structures of 1-(NCH-2'-S)-1,2-CBH, 1-(NCH-2'-CHS)-1,2-CBH, Cs [7-(NCH-2'-CHS)-7,8-CBH] - and -carboranes and 3-PhP-3-(4(7)-NCH-2'-S)--3,1,2-NiCBH and 3-PhP-3-(4(7)-NCH-2'-CHS)--3,1,2-NiCBH metallacarboranes were determined using single crystal X-ray diffraction.

New Azido Coumarins as Potential Agents for Fluorescent Labeling and Their "Click" Chemistry Reactions for the Conjugation with -Dodecaborate Anion.

Novel fluorescent 7-methoxy- and 7-(diethylamino)-coumarins modified with azido-group on the side chain have been synthesized. Their photophysical properties and single crystals structure characteristics have been studied. In order to demonstrate the possibilities of fluorescent labeling, obtained coumarins have been tested with -dodecaborate derivative bearing terminal alkynyl group.

Synthesis of Cobalt Bis(Dicarbollide)-Curcumin Conjugates for Potential Use in Boron Neutron Capture Therapy.

A series of novel cobalt bis(dicarbollide)-curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained.

Synthesis and Antibacterial Activity Studies of the Conjugates of Curcumin with -Dodecaborate and Cobalt Bis(Dicarbollide) Boron Clusters.

A series of novel conjugates of cobalt bis(dicarbollide) and -dodecaborate with curcumin were synthesized by copper(I)-catalyzed azide-alkyne cycloaddition. These conjugates were tested for antibacterial activity. It was shown that all derivatives are active when exposed to ATCC 10702 and are not active against Gram-negative microorganisms and at the maximum studied concentration of 1000 mg/L.

Nucleophilic addition reactions to nitrilium derivatives [BHNCCH] and [BHNCCHCH]. Synthesis and structures of -dodecaborate-based iminols, amides and amidines.

The synthesis of the acetonitrilium and propionitrilium derivatives of -dodecaborate [BH] was discussed. The nucleophilic addition reactions of water, alcohols and secondary amines to the activated triple bond of the nitrilium derivatives yielded the corresponding iminols, imidates and amidines. The obtained results were supported by X-ray diffraction studies and DFT calculations.

Synthesis of Zwitter-Ionic Conjugate of -Carborane with Cholesterol.

9-HC≡CCHMeN--7,8-CBH, a previously described carboranyl terminal alkyne, was used for the copper(I)-catalyzed azide-alkyne cycloaddition with azido-3β-cholesterol to form a novel zwitter-ionic conjugate of -carborane with cholesterol, bearing a 1,2,3-triazol fragment. The conjugate of -carborane with cholesterol, containing a charge-compensated group in the linker, can be used as a precursor for the preparation of liposomes for BNCT (Boron Neutron Capture Therapy). The solid-state molecular structure of a -carborane derivative with the 9-MeN(CH)MeN--7,8-CBH terminal dimethylamino group was determined by single-crystal X-ray diffraction.

Synthesis of Boronated Amidines by Addition of Amines to Nitrilium Derivative of Cobalt Bis(Dicarbollide).

A series of novel cobalt bis(dicarbollide) based amidines were synthesized by the nucleophilic addition of primary and secondary amines to highly activated B-N≡C-R triple bond of the propionitrilium derivative [8-EtC≡N-3,3'-Co(1,2-CBH)(1',2'-CBH)]. The reactions with primary amines result in the formation of mixtures of and isomers of amidines, whereas the reactions with secondary amines lead selectively to the -isomers. The crystal molecular structures of -[8-EtC(NMe)=HN-3,3'-Co(1,2-CBH)(1',2'-CBH)], -[8-EtC(NEt)=HN-3,3'-Co(1,2- CBH)(1',2'-CBH)] and -[8-EtC(NCH)=HN-3,3'-Co(1,2-CBH)(1',2'-CBH)] were determined by single crystal X-ray diffraction.

Effect of Phosphatidylcholine Nanosomes on Phospholipid Composition of the Plasma Membranes in Liver Cells and Blood Serum in Experimental Atherosclerosis.

Alimentary atherosclerosis is associated with a significant decrease in the content of phosphatidylcholine, the phospholipid that provides antioxidant protection, in the plasma membrane of liver cells, while the level of phosphatidic acid that initiates generation of superoxides, on the contrary, increases. The level of membrane phosphatidylserine, a target of the scavenger receptors, which initiates removal of damaged cells and modified lipoproteins from the circulation was also elevated. In the blood serum of rabbits receiving an atherogenic diet, the content of cardiolipin involved in the immune mechanisms of atherosclerosis development and a risk factor for thrombosis, sharply increased.

Liposomes containing dopamine entrapped in response to transmembrane ammonium sulfate gradient as carrier system for dopamine delivery into the brain of parkinsonian mice.

The active loading of liposomes with dopamine in response to an ammonium sulfate gradient was studied. This method can be regarded as a mean to more efficiently improve the liposomal dopamine/lipids ratio in comparison to conventional methods of liposome preparation. Trapping efficiency of dopamine into liposomes exhibiting a transmembrane ammonium sulfate gradient was shown to be dependent on liposome lipid composition, lipid concentration and temperature.

Interaction of N-(2-hydroxybenzyl)-omega-amino carbonic acids, novel amphipathic fatty acid derivatives, with membrane: partition coefficients.

The methods for partition coefficient (Kp) determination were developed for different concentrations of N-(2-hydroxybenzyl)-omega-amino carbonic acids, a new class of amphipathic fatty acid derivatives (An), their deutero (AnD) and bromine (AnBr) derivatives. To do this the following methods were used: 2H-NMR, equilibrium dialysis, centrifugation and fluorescence spectroscopy. Kp dependence on the An concentration is discussed.

Effect of novel aromatic derivative of GABA on lipid peroxidation in chronically morphinized rats.

Effect of novel aromatic GABA derivative (AFA) on lipid peroxidation (LP) was studied in the male rats of the Wistar strain. The morphine-received animals had the higher level of LP in blood plasma, decreased level of total antioxidant activity, the increased rate of LP in the ascorbate-induced system in liver homogenate. In the case of AFA administration with morphine, all the above mentioned effects were almost withdrawn.

N-(2-hydroxybenzyl)-omega-amino carbonic acids and their derivatives as tools for biochemical and biophysical investigations.

We propose N-(2-hydroxybenzyl)-omega-amino carbonic acids (An) as multifunctional probes for fatty acid metabolism studies. Multifunctionality could be achieved by introduction of different isotopes into An molecule. Deuteration of An results in probes for 2H-NMR membrane studies.

Haematoporphyrin derivatives: distribution in a living organism.

Pharmacokinetics of accumulation in organs and tissues was studied for two haematoporphyrin-based photosensitizers. These sensitizers, haematoporphyrin derivative (HpD) and an oligomeric haematoporphyrin (OHp), contained different amounts of monomeric fraction (25% and 5% respectively) and in OHp the macrocycles were bonded together with ether bonds. OHp was shown to accumulate in tumours in higher amounts than HpD.

Proteolytic fragment of protein kinase C (kinase M) phosphorylates in vitro phosphatidylinositol-4-phosphate.

Limited tryptic proteolysis of homogeneous protein kinase C induces the formation of a catalytically active fragment of 50 kDa (kinase M) which, unlike native PK C acquires the ability to phosphorylate PIP. Both ATP and GTP were found to be capable of serving as phosphate donors in this process. Incubation of purified kinase M with a preparation of rat brain membrane fraction enhanced the level of phosphorylation of PIP in the presence and in the absence of exogenous PIP.

Hematoporphyrin derivatives: an oligomeric composition study.

The oligomeric composition of HpD, Photofrin II and other hematoporphyrin derivatives useful for the diagnosis and therapy of tumors has been studied. Gel chromatographic procedures were used that excluded porphyrin aggregation. Photofrin and hematoporphyrin derivatives were shown to contain different quantities of monomer, dimer and other oligomeric porphyrins.

Synapsin I from human brain. Phosphorylation by Ca2+, phospholipid-dependent protein kinase.

Synapsin I has been isolated from human brain by a rapid and efficient purification technique, and its phosphorylation by human brain Ca2+, phospholipid-dependent protein kinase (protein kinase C) has been studied. The inhibitory effect of calmodulin on this process has been demonstrated. It is also found that non-esterified fatty acids and acidic phospholipids are inhibitory for synapsin I phosphorylation by Ca2+, calmodulin-dependent protein kinase II.