Boron clusters as a platform for new materials: composites of nucleic acids and oligofunctionalized carboranes (C2B10H12) and their assembly into functional nanoparticles

Kaniowski, Damian; Ebenryter-Olbińska, Katarzyna; Kulik, Katarzyna; Janczak, Slawomir; Maciaszek, Anna; Bednarska-Szczepaniak, Katarzyna; Nawrot, Barbara; Leśnikowski, Zbigniew J.

doi:10.1039/c9nr06550d

Cited by 24 publications

(51 citation statements)

References 31 publications

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“…technologies [6,7]. The hydrophobicity of boron clusters could improve the cell penetration of oligonucleotide constructs, including siRNA and antisense oligonucleotides.…”

Section: Synthesis Of Azido Derivatives Of Closo-dodecaboratementioning

confidence: 99%

Terminal Mono- and Bis-Conjugates of Oligonucleotides with Closo-Dodecaborate: Synthesis and Physico-Chemical Properties

Новопашина

Vorobyeva

Lomzov

et al. 2020

IJMS

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Oligonucleotide conjugates with boron clusters have found applications in different fields of molecular biology, biotechnology, and biomedicine as potential agents for boron neutron capture therapy, siRNA components, and antisense agents. Particularly, the closo-dodecaborate anion represents a high-boron-containing residue with remarkable chemical stability and low toxicity, and is suitable for the engineering of different constructs for biomedicine and molecular biology. In the present work, we synthesized novel oligonucleotide conjugates of closo-dodecaborate attached to the 5′-, 3′-, or both terminal positions of DNA, RNA, 2′-O-Me RNA, and 2′-F-Py RNA oligomers. For their synthesis, we employed click reaction with the azido derivative of closo-dodecaborate. The key physicochemical characteristics of the conjugates have been investigated using high-performance liquid chromatography, gel electrophoresis, UV thermal melting, and circular dichroism spectroscopy. Incorporation of closo-dodecaborate residues at the 3′-end of all oligomers stabilized their complementary complexes, whereas analogous 5′-modification decreased duplex stability. Two boron clusters attached to the opposite ends of the oligomer only slightly influence the stability of complementary complexes of RNA oligonucleotide and its 2′-O-methyl and 2′-fluoro analogs. On the contrary, the same modification of DNA oligonucleotides significantly destabilized the DNA/DNA duplex but gave a strong stabilization of the duplex with an RNA target. According to circular dichroism spectroscopy results, two terminal closo-dodecaborate residues cause a prominent structural rearrangement of complementary complexes with a substantial shift from the B-form to the A-form of the double helix. The revealed changes of key characteristics of oligonucleotides caused by incorporation of terminal boron clusters, such as the increase of hydrophobicity, change of duplex stability, and prominent structural changes for DNA conjugates, should be taken into account for the development of antisense oligonucleotides, siRNAs, or aptamers bearing boron clusters. These features may also be used for engineering of developing NA constructs with pre-defined properties.

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“…technologies [6,7]. The hydrophobicity of boron clusters could improve the cell penetration of oligonucleotide constructs, including siRNA and antisense oligonucleotides.…”

Section: Synthesis Of Azido Derivatives Of Closo-dodecaboratementioning

confidence: 99%

Terminal Mono- and Bis-Conjugates of Oligonucleotides with Closo-Dodecaborate: Synthesis and Physico-Chemical Properties

Новопашина

Vorobyeva

Lomzov

et al. 2020

IJMS

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“…This procedure does not proceed equally for all B-Hs, for instance, at the B (3,6) vertices, which are the most electron-deficient vertexes, their functionalization does not take place by using the same process at the other cluster's vertices [8,11]. Substitution on these positions can be achieved via the deboration-capping multistep reaction or via the metallation procedure [11-13. The diverse regioreactivity of o-carborane, has been exploited and adapted to make o-carborane an exceptional core for developing a large variety of multibranched molecules, globular macromolecules, dendrimers (Figure 2b), and so on [14][15][16][17][18]. Moreover, new versatile synthons have been explored through the multi-functionalization of B and Cc atoms jointly, which make the ocarborane clusters an exciting platform for new materials [6,8,[18][19][20][21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

“…Substitution on these positions can be achieved via the deboration-capping multistep reaction or via the metallation procedure [11-13. The diverse regioreactivity of o-carborane, has been exploited and adapted to make o-carborane an exceptional core for developing a large variety of multibranched molecules, globular macromolecules, dendrimers (Figure 2b), and so on [14][15][16][17][18]. Moreover, new versatile synthons have been explored through the multi-functionalization of B and Cc atoms jointly, which make the ocarborane clusters an exciting platform for new materials [6,8,[18][19][20][21][22][23][24][25]. On the other hand, the reactivity of m-carborane is less studied but for the Cc-H vertexes, which are less acidic as compared to the Cc-H vertexes of the o-isomer [10,26].…”

Section: Introductionmentioning

confidence: 99%

m-Carborane as a Novel Core for Periphery-Decorated Macromolecules

et al. 2020

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Closo m-C2B10H12 can perform as a novel core of globular periphery-decorated macromolecules. To do this, a new class of di and tetrabranched m-carborane derivatives has been synthesized by a judicious choice of the synthetic procedure, starting with 9,10-I2-1,7-closo-C2B10H10. The 2a-NPA (sum of the natural charges of the two bonded atoms) value for a bond, which is defined as the sum of the NPA charges of the two bonded atoms, matches the order of electrophilic reaction at the different cluster bonds of the icosahedral o-and m- carboranes that lead to the formation of B-I bonds. As for m-carborane, most of the 2a-NPA values of B-H vertexes are positive, and their functionalization is more challenging. The synthesis and full characterization of dibranched 9,10-R2-1,7-closo-carborane (R = CH2CHCH2, HO(CH2)3, Cl(CH2)3, TsO(CH2)3, C6H5COO(CH2)3, C6H5COO(CH2)3, N3(CH2)3, CH3CHCH, and C6H5C2N3(CH2)3) compounds as well as the tetrabranched 9,10-R2-1,7-R2-closo-C2B10H8 (R = CH2CHCH2, HO(CH2)3) are presented. The X-ray diffraction of 9,10-(HO(CH2)3)2-1,7-closo-C2B10H10 and 9,10-(CH3CHCH)2-1,7-closo-C2B10H10, as well as their Hirshfeld surface analysis and decomposed fingerprint plots, are described. These new reported tetrabranched m-carborane derivatives provide a sort of novel core for the synthesis of 3D radially grown periphery-decorated macromolecules that are different to the 2D radially grown core of the tetrabranched o-carborane framework.

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“…Oligonucleotide conjugates with boron clusters attract particular attention as tools for molecular biology, biotechnology, and biomedicine. Their fields of application include potential agents for boron neutron capture therapy (BNCT) (see, e.g., [1]), diagnostic tools and probes for molecular biology [2], siRNA components [3] and antisense agents [4][5][6], and a basis for the development of nanoconstructs and novel materials for modern nanotechnologies [6,7]. The hydrophobicity of boron clusters could improve the cell penetration of oligonucleotide constructs, including siRNA and antisense oligonucleotides.…”

Section: Introductionmentioning

confidence: 99%

“…So far, only one study has been published on the terminal oligonucleotide modifications by the boron clusters [10]. Along with that, most of the works on oligonucleotides bearing boron clusters deal with non-modified DNA oligonucleotides [4][5][6], with one exception for siRNA [3]. In the present work, we proposed a method employing the click chemistry for synthesizing novel DNA, RNA, and 2'-modified oligoribonucleotides conjugated with boron clusters as terminal 5'-, 3'-or dual modifications.…”

Section: Introductionmentioning

confidence: 99%

Terminal Mono- and Bis-Conjugates of Oligonucleotides with Closo-Dodecaborate: Synthesis and Physico-Chemical Properties

Новопашина

Vorobyeva

Lomzov

et al. 2020

Preprint

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Oligonucleotide conjugates with boron clusters have found applications in different fields of molecular biology, biotechnology, and biomedicine as potential agents for boron neutron capture therapy, siRNA components, and antisense agents. Particularly, closo-dodecaborate anion represents a high-boron containing residue with remarkable chemical stability and low toxicity, suitable for the engineering of different constructs for biomedicine and molecular biology. In the present work, we synthesized novel oligonucleotide conjugates of closo-dodecaborate attached to the 5'-, 3'-, or both terminal positions of DNA, RNA, 2'-O-Me RNA, and 2'-F-Py RNA oligomers. For their synthesis, we employed click reaction with the azido derivative of closo-dodecaborate. The key physicochemical characteristics of the conjugates have been investigated using high-performance liquid chromatography, gel electrophoresis, UV thermal melting, and circular dichroism spectroscopy. Incorporation of closo-dodecaborate residues at the 3'-end of all oligomers stabilized their complementary complexes, while analogous 5'-modification decreased duplex stability. Two boron clusters attached to the opposite ends of the oligomer only slightly influence the stability of complementary complexes of RNA oligonucleotide and its 2'-O-methyl and 2'-fluoro analogs. On the contrary, the same modification of DNA oligonucleotides significantly destabilized DNA/DNA duplex but gave a strong stabilization of the duplex with RNA target. According to CD spectroscopy results, two terminal closo-dodecaborate residues cause a prominent structural rearrangement of complementary complexes with a substantial shift from B-form to the A-form of the double helix. The revealed changes of key characteristics of oligonucleotides caused by incorporation of terminal boron clusters, such as the increase of hydrophobicity, change of duplex stability, and prominent structural changes for DNA conjugates, should be taken into account for the development of antisense oligonucleotides, siRNAs, or aptamers bearing boron clusters. These features may also be used for engineering of developing NA constructs with pre-defined properties.

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Boron clusters as a platform for new materials: composites of nucleic acids and oligofunctionalized carboranes (C₂B₁₀H₁₂) and their assembly into functional nanoparticles

Abstract: The building blocks based on boron cluster spanning two short DNA adapters assemble into functional nanoparticles due to the formation of DNA helices. They offer dual-action therapeutic potential, e.g., in the BNCT and gene expression regulation.

Cited by 24 publications

References 31 publications

Terminal Mono- and Bis-Conjugates of Oligonucleotides with Closo-Dodecaborate: Synthesis and Physico-Chemical Properties

Terminal Mono- and Bis-Conjugates of Oligonucleotides with Closo-Dodecaborate: Synthesis and Physico-Chemical Properties

m-Carborane as a Novel Core for Periphery-Decorated Macromolecules

Terminal Mono- and Bis-Conjugates of Oligonucleotides with Closo-Dodecaborate: Synthesis and Physico-Chemical Properties

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