Aggregation Behavior of Nucleoside−Boron Cluster Conjugates in Aqueous Solutions

Abstract

We report the first evidence that boron-containing nucleoside conjugates have a tendency to associate in water solutions. The size, charge, and exoskeletal pattern of the boron cluster can strongly influence the aggregation. The aggregation of nucleosides with attached boron clusters was observed using light scattering and atomic force microscopy techniques. Although the species containing either the bulky amphiphilic [3-cobalt(III) bis(1,2-dicarbollide)]- anion or the electroneutral dicarba-closo-dodecaboranyl moiety tend to form stable nanoparticles in aqueous solutions, the compounds bearing the smaller, negatively charged dicarba-nido-undecaboranyl moiety as well as the unmodified nucleosides do not aggregate. The light scattering measurements also showed that the aggregated species can interact with nonionic surfactant Triton X-100 in solution. The partition coefficients P in the water-octanol system correlate fairly well with the aggregation tendency observed by light scattering measurements. This finding allows us to predict the association behavior of boron-cluster-containing nucleosides on a qualitative level. The observed phenomenon can contribute to a better understanding of biological properties of boronated nucleosides and the design of boronated nucleoside-based drugs such as boron carriers for boron neutron capture therapy of tumors (BNCT) and antiviral agents.

Synthesis and in vitro antiviral activity of lipophilic pyrimidine nucleoside/carborane conjugates

“…Interestingly, low solubility and the tendency to precipitate in cell culture medium at concentrations above 500 µM was observed for compound 11 which bears a long, flexible spacer between the boron cluster and nucleobase, but not for compounds 7-10 [16]. The testing revealed low (compounds 7, 8) to moderate (compounds 9-11) cytotoxicity (Table 1) (Table 2).…”

Nitric Oxide Synthases Activation and Inhibition by Metallacarborane-Cluster-Based Isoform-Specific Affectors

“…This general procedure has already become a routine method for attachment of the cobalt bis(dicarbollide) moiety to substance via a diethylene glycol spacer [33–35, 43,48–52]. If the nucleophile is anion, the reaction produced anionic derivative (compounds 15 and 18 ); in the case of uncharged or thiourea-type nucleophiles betain-type zwitterion are formed (compounds 16 , 17 , 19 – 30 ).…”

Carboranylporphyrazines for anti-cancer therapies: synthesis and physicochemical properties

“…In the past 15 years, several BNCT (Boron Neutron Capture Therapy) agents [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] have been proposed, including boronated nucleosides [5][6][7][8][9], amino acids and peptides [10,11], phospholipids [12], monoclonal antibodies, liposomes [13][14][15], closomers [16,17], and dendrimers [18,19]. Tetrapyrrolic macrocycles, a vast class of biologically relevant compounds often employed as sensitizers in anti-cancer photomedical treatments (including photodynamic therapy (PDT) [20][21][22][23][24] and photothermal therapy (PTT) [25][26][27][28]), have also been derivatized with boron-containing functions for possible use in BNCT [20,[29][30][31]…”