Extraordinary Thermal Stability of an Oligodeoxynucleotide Octamer Constructed from Alternating 7‐Deaza‐7‐iodo guanine and 5‐Iodocytosine Base Pairs – DNA Duplex Stabilization by Halogen Bonds?

Abstract

A reinvestigation of the published X-ray crystal-structure analyses of 7-halogenated (Br, I) 8-aza-7-deaza-2'-deoxyguanosines Br(7) c(7) z(8) Gd ; 1a and I(7) c(7) z(8) Gd , 1b, as well as of the structurally related 7-deaza-7-iodo-2'-deoxy-β-D-ribofuranosyladenine (β-I(7) c(7) Ad ; 2=6e in Table 1) and its α-D-anomer (α-I(7) c(7) Ad ; 3) clearly revealed the existence of halogen bonds between corresponding halogen substituents and the adjacent N(3)-atoms of neighboring nucleoside molecules within the single crystals. These halogen bonds can be rationalized by the presence of a region of positive electrostatic potential, the σ-hole, on the outermost portion the halogen's surface, while the three unshared pairs of electrons produce a belt of negative electrostatic potential around the central part of the halogen substituent. The N(3) atoms of the halogenated nucleosides carry a partial negative charge. This novel type of bonding between nucleosides was tentatively used to explain the extraordinary high stability of oligodeoxynucleotides constructed from halogenated nucleotide building blocks.

Synthesis and Evolution of a Threose Nucleic Acid Aptamer Bearing 7-Deaza-7-Substituted Guanosine Residues

“…Although the rationale for 7I-G was to impede Hoogsteen pairing of the G:G type, this need not carry over to other types of Hoogsteen pairing. Thus, while G:G Hoogsteen pairing is anticipated and observed to be blocked by the iodo group of 7I-G due to both steric and electronic effects, the opposite is anticipated for 7I-G:T. Here the key underlying feature concerns the electropositive “sigma-hole” found on halogen atoms, and the ability of these structural elements to interact with electro­negative entities on other atoms or molecules, including lone pairs of electrons on hetero­atoms, to form weak non-covalent bonding interactions. − In the present case, the electropositive nature of the iodo group terminus is displayed in Figure a. Partial optimization of a TNA:DNA dinucleotide duplex (Figure b) at the B3LYP/MidiX level resulted in a 7I-tG:dT Hoogsteen pair with an N–N distance of 9.02 Å (identical to B-DNA) and a 7-iodo---2-oxygen distance of 2.99 Å, consistent with known favorable halogen–oxygen electrostatic/bonding interaction distances.…”