Anionic boron cluster compound
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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.
Anionic boron cluster compounds have recently made their way into many areas including medicinal chemistry and sensors due to favorable physical-chemical properties and their various biological activity. Notwithstanding the inherent chirality of these compounds, the exploration of the properties and activity of individual enantiomers remains uncharted territory. The permanent delocalized negative charge enables the electrophoretic mobility of these compounds. Thus, chiral electrophoresis, characterized by minimal consumption of chemicals and a sample, emerges as a promising candidate for a reliable quality control tool. The primary attempts in aqueous electrolytes showed some difficulties related to the limited solubility of these analytes. This study meticulously investigates the electrophoretic behavior and chiral separation of anionic [7,8-nido-C2B9H11]- and cobalt bis(dicarbollide)(1-) derivatives using a methanolic non-aqueous electrolyte with numerous derivatives of cyclodextrins. Randomly substituted hydroxypropyl-β-, methyl-β-, and hydroxypropyl-γ-cyclodextrins were identified as the most effective chiral selectors. The chiral separations delineated herein surpass previously published results in capillary electrophoresis in terms of resolution, peak shape, and the number of theoretical plates. Furthermore, the application of (2-hydroxy-3-N,N,N-trimethylamino)propylated β-cyclodextrin in non-aqueous environment resulted in the chiral separation of seven recently synthesized amino cobalt bis(dicarbollide)(1-) derivatives; thereby, reinforcing the extensive applicability of the developed methodology for different structural types of anionic cobalt bis(dicarbollides)(1-). These results qualify non-aqueous electrophoresis as a valuable tool for the enantiomeric purity control of anionic boron cluster compounds with respect to their further use in various areas.
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Boron cluster compounds are extensively studied due to their possible use in medicinal chemistry, mainly in the boron neutron capture anticancer therapy and as new innovative pharmacophores. Concerning this research, the chiral separations of exceptionally stable anionic 7,8-dicarba-nido-undecaborate(1-) and metal bis(dicarbollide(1-) derivatives with asymmetric substitutions remain the unsolved challenge of the chiral chromatography nowadays. Although the successful enantioseparation of some anionic 7,8-dicarba-nido-undecaborate(1-) ion derivatives were achieved in CZE with native β-cyclodextrins, it has not been observed with HPLC, yet. This study aimed to systematically investigate the enantioseparation of selected compounds in HPLC using native β-cyclodextrin and brominated β-cyclodextrin. The findings revealed positively charged strong adsorption sites on a stationary phase, identified as the cationic metal impurities in the silica-gel backbone. All the anionic species under the study were at least partially enantioseparated when a chelating agent blocked these cationic sites. Consequently, the first-ever HPLC enantioseparations of the 7,8-dicarba-nido-undecaborates(1-) were achieved. The brominated β-cyclodextrin seemed to be a better chiral selector for separation of these species, whereas the native β-cyclodextrin separated the anionic cobalt bis(dicarbollide(1-). The results of this study bring new information concerning the chiral separation of anionic boron clusters and might be used in the chiral method development process on other chiral selectors. Furthermore, the possibility of chiral separation of these species could influence the ongoing research areas of anionic boron clusters.
The continuous expansion of research in the field of stable carboranes and their wide potential in the drug design require carrying out fundamental studies regarding their chiral separations. Although supercritical fluid chromatography (SFC) is a viable technique for fast enantioseparations, no investigation concerning boron cluster compounds has been done yet. We aimed at the development of a straightforward method enabling chiral separations of racemic mixtures of anionic cluster carboranes and metallacarboranes that represent an analytical challenge. The fast gradient screening testing nine polysaccharide-based columns was used. The key parameters affecting the selectivity were the type of chiral selector, the type of alcohol, and the base in cosolvent. Moreover, the addition of acetonitrile or water to the cosolvent was identified as an effective tool for decreasing the analysis time while preserving the resolution. After the optimization, the chiral separations of 19 out of 20 selected compounds were achieved in less than 10 min. These results demonstrate the clear advantage of SFC over chiral separations using HPLC in terms of both analysis time and structural variety of successfully separated compounds.
