ABSTRACT
Four different carboranethiol derivatives were used to modify the surfaces of gold nanoparticles and flat gold films. The novel materials engendered from these modifications are extraordinarily stable species with surfaces that support self-assembled monolayers of 1-(HS)-1,2-C2B10H11, 1,2-(HS)2-1,2-C2B10H10, 1,12-(HS)2-1,12-C2B10H10, and 9,12-(HS)2-1,2-C2B10H10, respectively. Surprisingly, characterization of these materials revealed that a number of molecules of the carboranethiol derivatives are incorporated inside the nanoparticles. This structural feature was studied using a number of techniques, including X-ray photoelectron spectroscopy (XPS), UV-vis, and IR spectroscopies. Thermal desorption experiments show that carborane molecules detach and leave the nanoparticle surface mostly as 1,2-C2B10H10 isotopic clusters, leaving sulfur atoms bound to the gold surface. The surfaces of both the gold nanoparticles and the flat gold films are densely packed with carboranethiolate units. One carborane cluster molecule occupies an area of six to seven surface gold atoms of the nanoparticle and eight surface gold atoms of the flat film. XPS data showed that molecules of 1,12-(HS)2-1,12-C2B10H10 bind to the flat gold surface with only half of the thiol groups due to the steric demands of the icosahedral carborane skeleton. Electrochemical measurements indicate complete coverage of the modified gold surfaces with the carboranethiol molecules.
Subject(s)
Boron Compounds/chemistry , Gold/chemistry , Sulfhydryl Compounds/chemistry , Electrochemistry , Membranes, Artificial , Models, Molecular , Nanostructures/chemistry , Particle Size , Sensitivity and Specificity , Spectrophotometry , Spectrophotometry, Infrared/methods , Surface Properties , Time Factors , Wettability , X-RaysSubject(s)
Cobalt/chemistry , DNA/chemistry , Nucleosides/chemistry , Oligodeoxyribonucleotides/chemistry , Organometallic Compounds/chemistry , Animals , Base Sequence , Cell Line , Chlorocebus aethiops , Cytomegalovirus/genetics , DNA/genetics , Humans , Inhibitory Concentration 50 , Molecular Structure , Nucleosides/toxicity , Oligodeoxyribonucleotides/genetics , Polymerase Chain ReactionABSTRACT
Boron neutron capture therapy (BNCT) is an experimental therapeutic modality combining a boron pharmaceutical with neutron irradiation. 4-Dihydroxyborylphenylalanine (L-BPA) synthesised via the asymmetric pathway by Malan and Morin [Synlett. 167-168 (1996)] was developed to be the boron containing pharmaceutical in the first series of Finnish BNCT clinical trials. The final product was >98.5% chemically pure L-BPA with L-phenylalanine and L-tyrosine as the residual impurities. The solubility of L-BPA was enhanced by complex formation with fructose (BPA-F). The pH and osmolarity of the BPA-F preparation is in the physiological range. Careful attention was given to the pharmaceutical quality of the BPA-F preparations. Prior to starting clinical trials the acute toxicity of L-BPA was studied in male albino Sprague-Dawley rats. In accordance with earlier studies no adverse effects were observed. After completion of the development work L-BPA solution was administered to brain tumour patients in conjunction with clinical studies for development and testing of BPA-based BNCT. No clinically significant adverse events attributable to the L-BPA i.v. infusions were observed. We conclude that our synthesis development, complementary preclinical and clinical observations justify the safe use of L-BPA up to clinical phase III studies with L-BPA produced by the asymmetric pathway, originally presented by Malan and Morin in 1996.