Halogen Bonding in DNA Base Pairs

Abstract

Halogen bonding (R-X···Y) is a qualitative analogue of hydrogen bonding that may prove useful in the rational design of artificial proteins and nucleotides. We explore halogen-bonded DNA base pairs containing modified guanine, cytosine, adenine and thymine nucleosides. The structures and stabilities of the halogenated systems are compared to the normal hydrogen bonded base pairs. In most cases, energetically stable, coplanar structures are identified. In the most favorable cases, halogenated base pair stabilities are within 2 kcal mol(-1) of the hydrogen bonded analogues. Among the halogens X = Cl, Br, and I, bromine is best suited for inclusion in these biological systems because it possesses the best combination of polarizability and steric suitability. We find that the most stable structures result from a single substitution of a hydrogen bond for a halogen bond in dA:dT and dG:dC base pairs, which allows 1 or 2 hydrogen bonds, respectively, to complement the halogen bond.

Abnormal synergistic effects between Lewis acid–base interaction and halogen bond in F3B···NCX···NCM

“…Halogen bond [1], a noncovalent interaction between an electron donor and a covalently bonded halogen atom acting as an electron acceptor, has attracted an increasing attention recently [2][3][4][5][6][7][8], because it can act as a molecular linker in molecular recognition [9][10][11], and material science [12][13][14]. Similar with hydrogen bond, halogen bond also exhibits the cooperative effect, which is responsible for its potential applications in crystal structures and supramolecular chemistry.…”

Selenium‐Mediated Dehalogenation of Halogenated Nucleosides and its Relevance to the DNA Repair Pathway

“…Thes ingle-crystal X-ray structures indicate that the chalcogen atoms in 15 and 16 interact with iodine in IU to form the halogen-bonded (X-bonded) adducts 17 and 18, respectively ( Figure 4A-C). [11] Although theoretical investigations predicted possible XB between the nucleobases, [12] 17 and 18 provide clear experimental evidence for X-bonded systems involving ah alogenated nucleobase.T he CÀIb ond (2.097 ) in 18 is elongated ( Figure 4C) as compared to that in IU (2.052 , see Figure S10). As reported earlier for other X-bonded systems, [13] the elongation of the CÀIb ond is due to the donation of electron density by the selenium atom to the anti-bonding s*orbital of the CÀIb ond.…”

Role of Weak Hydrogen Bonds and Halogen Bonds in 5-Halo-1,3-dimethyluracils and Their Cocrystals—A Combined Experimental and Computational Study

“…HBs in halogenated uracils have been investigated extensively by different research groups. [6][7][8][9][10][11][12][13] In biological systems, the different 5-halouracils, similar in size to thymine (5-methyluracil), are expected to exhibit base pairing which closely mimics the WatsonCrick thymine-adenine duplex stabilization in DNA. However, the variation of halogen from fluoro to iodo may substantially affect the chemical and electronic properties of the nucleobase, and therefore its incorporation into DNA and in vivo activity.…”