Nucleoside Modification with Boron Clusters and Their Metal Complexes

Blazej A. Wojtczak1, Agnieszka B. Olejniczak1, Zbigniew J. Lesnikowski1

1 Institute for Medical Biology, Polish Academy of Sciences, Laboratory of Molecular Virology and Biological Chemistry, Lodz, Poland
Publication Name:  Current Protocols in Nucleic Acid Chemistry
Unit Number:  Unit 4.37
DOI:  10.1002/0471142700.nc0437s38
Online Posting Date:  September, 2009
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General methods for the synthesis of nucleosides modified with borane clusters and metallacarborane complexes are presented. These include: (1) the click chemistry approach based on Huisgen 1,3‐dipolar cycloaddition and (2) tethering of the metallacarborane group to the aglycone of a nucleoside via a dioxane ring opening in oxonium metallacarborane derivatives. The proposed methodologies broaden the availability of nucleoside‐borane cluster conjugates and open up new areas for their applications. Curr. Protoc. Nucleic Acid Chem. 38:4.37.1‐4.37.26. © 2009 by John Wiley & Sons, Inc.

Keywords: boron clusters; metal complexes; click chemistry; nucleosides; bioorganic‐inorganic materials

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Table of Contents

  • Introduction
  • Basic Protocol 1: Preparation of Nucleoside‐Boron Cluster Conjugates via Click Chemical Ligation Method
  • Basic Protocol 2: Preparation of Nucleoside‐Boron Cluster Conjugates via Cyclic Ether Ring Opening in Cyclic Ether Boron Cluster Oxonium Adducts
  • Commentary
  • Literature Cited
  • Figures
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Basic Protocol 1: Preparation of Nucleoside‐Boron Cluster Conjugates via Click Chemical Ligation Method

  • 10‐Dioxane‐7,8‐dicarba‐nido‐undecaborane zwitterion ( S.11) (J. Plešek, pers. comm.)
  • Sodium azide, pure
  • Dimethylformamide, anhydrous, 99.5% pure
  • Methylene chloride (CH 2Cl 2), analytical grade
  • Methanol (CH 3OH), analytical grade
  • Silica gel 60 (230 to 400 mesh)
  • PdCl 2
  • 8‐Dioxane‐[3‐cobalt bis(1,2‐dicarbollide)] zwitterion ( S.13) or 8‐dioxane‐[3‐iron bis(1,2‐dicarbollide)] zwitterion ( S.14)
  • 60% sodium hydride (NaH) suspension in mineral oil
  • Propargyl alcohol, 99% pure
  • Toluene, anhydrous, 99.7% pure
  • Argon gas
  • 7,8‐Dicarba‐nido‐undecaborane anion ( S.18) (Hawthorne et al., )
  • 98% sulfuric acid
  • Dioxane, anhydrous
  • 99% dimethyl sulfate
  • 30% and 50% ethanol (EtOH), analytical grade
  • [3‐Iron bis(1,2‐dicarbollide)](‐1)ate anion ( S.20) (Hawthorne et al., ; Sivaev and Bregadze, )
  • Nitrogen gas
  • Benzene, analytical grade
  • Hexane, analytical grade
  • Pentynyl tosylate (Rong et al., )
  • Thymidine ( S.21)
  • Potassium carbonate, analytical grade
  • Diethylene glycol di(p‐toluenesulfonate) (Chen and Barker, )
  • tert‐Butanol, analytical grade
  • Water, deionized (Millipore)
  • 100 mM CuSO 4⋅5H 2O
  • 100 mM potassium ascorbate
  • TLC plates, 20 × 20–cm, pre‐coated with 0.2‐mm layer thickness silica gel 60 F254
  • Evaporator with vacuum (SpeedVac Plus SC110A Savant)
  • 1.5 × 20–cm and 2.5 × 20–cm sintered glass columns
  • Magnetic stir bar and plate
  • Separatory funnel
  • Filter paper (e.g., Whatman)
  • 80°C heating block
  • Reflux condenser
  • Sintered disc filter funnel (e.g., Schott G3)
  • 10‐mL syringes
  • Water aspirator
  • Vacuum pump
  • Lyophilizer

Basic Protocol 2: Preparation of Nucleoside‐Boron Cluster Conjugates via Cyclic Ether Ring Opening in Cyclic Ether Boron Cluster Oxonium Adducts

  • 3′,5′‐protected 2′‐deoxyribonucleoside S.23, S.26, S.29, or S.32 (0.80 mmol)
  • 8‐dioxane‐[3‐cobalt bis(dicarbollide)] zwitterion ( S.13)
  • Phosphorus (V) oxide (P 2O 5), 98% pure
  • Anhydrous toluene
  • Argon gas
  • 60% sodium hydride (NaH) suspension in mineral oil
  • Silica gel
  • Methylene chloride (CH 2Cl 2), analytical grade
  • Acetonitrile (CH 3CN), anhydrous
  • 3′,5′‐protected 2′‐deoxyadenosine S.32
  • 8‐dioxane‐[3‐iron bis(dicarbollide)] zwitterion S.14
  • 2′‐Deoxyadenosine
  • 2′‐Deoxycytidine
  • 2′‐Deoxyguanosine
  • 2′‐Deoxythymidine
  • Tetrahydrofuran (THF), anhydrous
  • 1 M tetra‐n‐butylammonium fluoride (TBAF)
  • Ethyl acetate (EtOAc), analytical grade, absolute
  • Magnesium sulfate (Mg 2SO 4), anhydrous, pure
  • Flasks with stoppers
  • Vacuum oil pump
  • Magnetic stir bar and heating plate
  • Water aspirator with vacuum attached
  • 3.5 × 15–cm glass chromatography columns
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Literature Cited

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