Synthesis and EPR Studies of 2′‐Deoxyuridines with Alkynyl, Rodlike Linkages

• Published in: Chemistry : a European journal Vol. 15; no. 31; pp. 7569 - 7577
• Main Authors: Sniady, Adam, Sevilla, Michael D., Meneni, Srinivasarao, Lis, Tadeusz, Szafert, Slawomir, Khanduri, Deepthi, Finke, John M., Dembinski, Roman
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 03.08.2009; Wiley
• Subjects: alkynes; Alkynes - chemical synthesis; Alkynes - chemistry; Catalysis; Chemistry; Chemistry, Multidisciplinary; Copper - chemistry; Cross-Linking Reagents - chemical synthesis; Cross-Linking Reagents - chemistry; Crystallography, X-Ray; Deoxyuridine - analogs & derivatives; Deoxyuridine - chemical synthesis; Deoxyuridine - chemistry; deoxyuridines; DNA - chemistry; electron delocalization; Electron Spin Resonance Spectroscopy; EPR spectroscopy; furopyrimidine; Iodides - chemistry; Molecular Conformation; Molecular Structure; nucleosides; Physical Sciences; Science & Technology; ELECTRON-SPIN-RESONANCE; ACID; MOLECULAR WIRES; RADICAL IONS; alkynes; URACIL; furopyrimidine; NUCLEOSIDE; nucleosides; COVALENT ANALOGS; DNA BASE-PAIRS; deoxyuridines; electron delocalization; DERIVATIVES; EPR spectroscopy; FURANO PYRIMIDINES
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200900481

Sonogashira coupling of diacetyl 5‐ethynyl‐2′‐deoxyuridine with diacetyl 5‐iodo‐2′‐deoxyuridine gave the acylated ethynediyl‐linked 2′‐deoxyuridine dimer (3 b; 63 %), which was deprotected with ammonia/methanol to give ethynediyl‐linked 2′‐deoxyuridines (3 a; 79 %). Treatment of 5‐ethynyl‐2′‐deoxyuridine (1 a) with 5‐iodo‐2′‐deoxyuridine gave the furopyrimidine linked to 2′‐deoxyuridine (78 %). Catalytic oxidative coupling of 1 a (O2, CuI, Pd/C, N,N‐dimethylformamide) gave butadiynediyl‐linked 2′‐deoxyuridines (4; 84 %). Double Sonogashira coupling of 5‐iodo‐2′‐deoxyuridine with 1,4‐diethynylbenzene gave 1,4‐phenylenediethynediyl‐bridged 2′‐deoxyuridines (5; 83 %). Cu‐catalyzed cycloisomerization of dimers 4 and 5 gave their furopyrimidine derivatives. One‐electron addition to 1 a, 3 a, and 4 gave the anion radical, the EPR spectra of which showed that the unpaired electron is largely localized at C6 of one uracil ring (17 G doublet) at 77 K. The EPR spectra of the one‐electron‐oxidized derivatives of ethynediyl‐ and butadiynediyl‐linked uridines 3 a and 4 at 77 K showed that the unpaired electron is delocalized over both rings. Therefore, structures 3 a and 4 provide an efficient electronic link for hole conduction between the uracil rings. However, for the excess electron, an activation barrier prevents coupling to both rings. These dimeric structures could provide a gate that would separate hole transfer from electron transport between strands in DNA systems. In the crystal structure of acylated dimer 3 b, the bases were found in the anti position relative to each other across the ethynyl link, and similar anti conformation was preserved in the derived furopyrimidine–deoxyuridine dinucleoside. One of two ways: Alkyne‐tethered dinucleosides have been shown to display two distinct behaviors; when reduced, the electron is localized on only one ring, whereas if they are oxidized the electron is delocalized across both rings (see figure). This effect could be used as a gate that separates hole and electron transport between strands in DNA systems.