"Chemical ligation": a versatile method for nucleoside modification with boron clusters

A general approach to the synthesis of nucleoside conjugates containing carborane and metallocarborane complexes, based on Huisgen 1,3-dipolar cycloaddition ("chemical ligation"), is described. Boron-cluster-donors bearing terminal azide or ethynyl groups were prepared in the ring-opening reaction of dioxane-boron-cluster adducts and an azide anion or suitable alkynol-derived alcoholate nucleophile. Analogous derivatives bearing terminal sulfhydryl groups were also prepared. Nucleosides with various spacers containing terminal azide or ethynyl groups, located within nucleobases or sugar residues, were used as boron-cluster acceptors. The proposed methodology provides a convenient way to synthesize libraries of boron-cluster-modified nucleosides for various applications.     

Synthesis of Dodeca(Thymidine Phosphate) Containing (o-Carboran-1-yl)Methylphosphonate Internucleotide Linkage

Abstract

The synthesis of dodeca(thymidylic phosphate) containing 3′-end (o-carboran-1-yl)methylphosphonate group instead of natural phosphodiester internucleotide linkage is described.     

Synthesis and Anti-HIV-1 Reverse Transcriptase Activity of Triphosphates of Penciclovir and β-D-Dioxolane-Guanine

Abstract

The synthesis of R- and S-9-(4-Hydroxy-3-hydroxymethyl-but-l-yl)guanine (PCV) and (?)-β-D-dioxolane-guanine (DXG) triphosphate and their enzyme inhibitory activity is descibed.     

Boron Clusters as a Platform for New Materials: Synthesis of Functionalized o‐Carborane (C2B10H12) Derivatives Incorporating DNA Fragments

A synthetic strategy for functionalization of the three vertices of o‐carborane and the attachment of the obtained triped to the solid support was developed. Further functionalization of the triped with short DNA sequences by automated DNA synthesis was achieved. The proposed methodology is a first example of boron cluster chemistry on a solid support opening new perspectives in boron cluster functionalization.     

General method for the synthesis of 2′-O-carboranyl-nucleosides

The carboranyl cage is a new modifying entity for nucleosides, DNA oligonucleotides, and other biomolecules. Herein, the first reliable method for the synthesis of nucleosides modified with a carborane cluster at the 2′-position is described.     

Synthesis of closo-dodecaborate based nucleoside conjugates

The first conjugates of closo-dodecaborate anion with nucleoside-thymidine were synthesized. The nucleophilic cleavage of dioxonium derivative of closo-dodecaborate by 3′,5′-bis(t-butyldimethylsilyl)-thymidine and “click” reaction between B₁₂-based azide and 3N-(4-pentyn-1-yl)thymidine were appeared as convenient approaches towards the synthesis of this new class of nucleoside-based boron cluster conjugates.     

Synthesis of adenosine containing carborane modification

The carboranyl cage is a new modifying entity for nucleosides and DNA-oligonucleotides. Most of carborane–nucleoside conjugates described so far belong to pyrimidine series. Herein, the first synthesis of adenosine, nucleoside containing purine nucleic base, modified with carborane cluster, is described.     

Aggregation behavior of nucleoside-boron cluster conjugates in aqueous solutions

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.