Functionalized Silver‐Ion‐Mediated α‐dC/β‐dC Hybrid Base Pairs with Exceptional Stability: α‐d‐5‐Iodo‐2′‐Deoxycytidine and Its Octadiynyl Derivative in Metal DNA

Abstract

Silver-mediated a-dC-Ag + -b-dC hybrid base pairs decoratedw ith 5-iodo-o r5 -octadiynyl residues are well accommodated in duplex DNA.Astrong T m increase and favorable thermodynamic data for duplex DNA were observed after addition of silver ions. The phenomenon is particularly obvious when both nucleobaseso ft he base pairs are functionalized. Neithert he positiono ft he base pair,n or the type of 5-substituenth ad an egative influence. On the contrary, functionalization of conventional silver-mediated b-dC-Ag + -b-dC homo base pairs showedanegative impact induced by the bulky substituents.T ot his end, cytosine modified 12-mer oligodeoxynucleotidesw ere prepared by solid-phase synthesis employing new a-anomeric 2'-deoxycytidine phosphoramidites. Am ultigram scale synthesis was developed for 5-iodo-a-d-2'-deoxycytidine (1)e mploying the direct glycosylation of cytosine with Hoffer's a-d-halogenose followed by separation of anomeric DMT nucleosides. Regarding base-pair stability and functionalization silver-mediated a/b-dC hybrid base pairs were found to be superior to b/b-dC homo pairs. According to their extraordinary properties, they might find applicationsi nD NA diagnostics, materials cience, or nanotechnology.[a] Dr.

Heterochiral DNA with Complementary Strands with α‐d and β‐d Configurations: Hydrogen‐Bonded and Silver‐Mediated Base Pairs with Impact of 7‐Deazapurines Replacing Purines

“…Oligonucleotides [22] -ODN-14 a- ODN-19 b-5'-d(AGTATT1ACCTA) [23] 3731. 7 A corresponds to 7-deaza-2'-deoxyadenosine, 7 G corresponds to 7-deaza-2'-deoxyguanosine, 1 corresponds to 5-iodo-2'-deoxycytidine, and 2 correspondst oa-5-iodo-2'-deoxycytidine.…”

“…7 A corresponds to 7-deaza-2'-deoxyadenosine, 7 G corresponds to 7-deaza-2'-deoxyguanosine, 1 corresponds to 5-iodo-2'-deoxycytidine, and 2 correspondst oa-5-iodo-2'-deoxycytidine. [23] tion, was used as ar eference compound. In the heterochiral duplex with parallel chain orientation in one of the two strands, all b-d nucleosides were replaced by their a-d anomers, resulting in the heterochiral duplex a…”

“…The purity of all oligonucleotides was confirmed by RP-18 HPLC (see Figures S2-S23 in the Supporting Information) and MALDI-TOF MS ( Table 1). The extinction coefficients e 260 (H 2 O) of the nucleosides are as follows:d A1 5400, dG 11 700, dT 8800, dC 7300, a-dC 7300, a-dA 15 400, a-dT 8800, a-dG 11 700, 7 A8 100, [22] 7 G13400, [44] 5-I-dC 3100 (MeOH), [23] and a-5-I-dC 3400 dm 3 mol À1 cm À1 (MeOH). [23] The extinction coefficients of the oligonucleotides were calculated from the sum of the extinction coefficients of the nucleoside constituents considering the hypochromic changes for the particular single General procedure for the stoichiometric titration experiments AA gNO 3 stock solution (2 mL) was added stepwise to solution containing 2.5 mm + 2.5 mm single-stranded oligonucleotides in 100 mm NaOAc and 10 mm Mg(OAc) 2 buffer (1 mL, pH 7.4) to obtain 0.2 equiv of silver ions/duplex.…”

“…[33] Recently,w e showedt hat the anomeric heterochiral a-dC•b-dC pairi sm ore stable than the homochiral b-dC•b-dC and a-dC•a-dC pairs. [23,34] The number of bound silver ions per base pair was determined by spectrophotometric titration:O ne or two silver ions were found to be present in the metal-mediated base pairs. Furthermore, it was observedt hat not only dC•dC mismatchesf orm silver-mediated base pairs, because stable duplexesw ere also generated after the addition of silver ions to mismatches of dC with dT, [34,35] dA, [34] or 7-deaza-dA.…”

“…[25] 7 A corresponds to 7-deaza-2'-deoxyadenosine, 7 G corresponds to 7-deaza-2'-deoxyguanosine, 1 corresponds to 5-iodo-2'-deoxycytidine, and 2 corresponds to a-5-iodo-2'-deoxycytidine. [23] ds corresponds to double-strandedD NA. n.m.referst on ot measured. )…”