Nucleoside–Metallacarborane Conjugates for Base‐Specific Metal Labeling of DNA

Abstract

A general approach to the synthesis of nucleoside conjugates between derivatives of thymidine (T), 2′‐O‐deoxycytidine (dC), 2′‐O‐deoxyadenosine (dA), and 2′‐O‐deoxyguanosine (dG), and metallacarborane complexes is described. Metallacarborane–nucleoside derivatives are prepared by reaction of the dioxane–metallacarborane adduct with a base‐activated 3′,5′‐protected nucleoside. In the case of T and dG a mixture of regioisomers, which is easily separable by chromatographic methods, is obtained, thus yielding a series of modifications containing metallacarborane groups at the 2‐O, 3‐N, 4‐O and 1‐N, 2‐N, 6‐O locations, respectively; dC and dA are alkylated at the exo‐amino function. The proposed methodology provides a route for the synthesis and study of nucleic acids modified with metallacarboranes at designated locations and a versatile approach to the incorporation of metals into DNA.

Adenosine and 2′‐Deoxyadenosine Modified with Boron Cluster Pharmacophores as New Classes of Human Blood Platelet Function Modulators

“…2'-O-[(para-Carboran-1-yl)propyleneoxymethyl]adenosine (1) [28] and 6-N-{5-[3-cobalt bis(1,2-dicarbollide)-8-yl]-3-oxapentoxy}-2'-deoxyadenosine (2) [29] ( Figure 1) were obtained as previously described. 6-N-{5- [7,8-nido-Carboran-10-yl]-3-oxapentoxy}adenosine (6) was prepared as described for 2 by the alkylation of fully protected 2',3',5'-O,O,O-tri-(tert-butyldimethylsilyl)adenosine (3) at the N6 position with 10-dioxane-7,8-nidocarborane (4) [30] (Scheme 1).…”

“…Data were expressed as mean value AE standard deviation (SD); p values < 0.05 are considered significant. (1) [28] and 6-N-{5-[3-cobalt bis(1,2-dicarbollide)-8-yl]-3-oxapentoxy}-2'-deoxyadenosine (2) [29] were obtained as described previously. Synthesis of 2',3',5'-O,O,O-tri-(tert-butyldimethylsilyl)adenosine (3) was performed according to published procedure.…”

Metallacarboranes as Labels for Multipotential Electrochemical Coding of DNA. [3‐Chromium bis(dicarbollide)](‐1)ate and Its Nucleoside Conjugates

“…Indeed, simple reaction of 2, without base activation, performed in a mixture of CHCl 3 /CH 3 CN (1 : 1, v/v) with twofold molar excess of 3, for 36 hours at 60 (4) with a reasonable, 37% preparative yield (Method A). In the second approach, 2 was activated with 1.5 molar excess of sodium hydride followed by treatment with 1.5 molar excess of 3 as described previously for alkylation of nucleosides with dioxane/ metallacarborane adduct containing cobalt [18], providing 4 with 44% preparative yield. The reaction was performed in toluene as reaction medium (Method B).…”

“…The metallacarborane/2'-deoxyadenosine conjugate containing chromium (5) was synthesized via dioxane ring opening in cyclic oxonium derivatives of [(3,3'-chromium-1,2,1',2'-dicarbollide)] (À 1)]ate ion (3) by 3',5'-protected 2'-deoxyadenosine (2) [18]. Briefly, first 5'-and 3'-hydroxyl functions of 2'-deoxyadenosine (1) were protected.…”

Nucleoside-metallacarborane conjugates - synthesis of a uridine - bearing 3,3,3-(CO)3-closo-3,1,2-ReC2B9H10 complex

“…Herein, a method for the synthesis of 2′-O-(3,3,3-tricarbonyl-closo-3,1,2-ReC 2 B 9 H 10 )methyluridine, a novel type of nucleoside-metallacarborane conjugate, is proposed. The availability of this type of molecule, along with the availability of previously published nucleoside conjugates containing bis-dicarbadodecaborane complexes of cobalt, iron, and chromium [1][2][3][4] , facilitates studies on the medical applications of nucleosides bearing metals. The recent significant progress in the chemistry of rhenium and technetium supports their applications in diagnostic and therapeutic nuclear medicine.…”