A review of heavy metal cation binding to deoxyribonucleic acids for the creation of chemical sensors

Abstract

Various human activities lead to the pollution of ground, drinking, and wastewater with toxic metals. It is well known that metal ions preferentially bind to DNA phosphate backbones or DNA nucleobases, or both. Foreman et al. (Environ Toxicol Chem 30(8):1810-1818, 2011) reported the use of a DNA-dye based assay suitable for use as a toxicity test for potable environmental water. They compared the results of this test with the responses of live-organism bioassays. The DNA-based demonstrated that the loss of SYBR Green I fluorescence dye bound to calf thymus DNA was proportional to the toxicity of the water sample. However, this report raised questions about the mechanism that formed the basis of this quasi-quantitatively test. In this review, we identify the unique and preferred DNA-binding sites of individual metals. We show how highly sensitive and selective DNA-based sensors can be designed that contain multiple binding sites for 21 heavy metal cations that bind to DNA and change its structure, consistent with the release of the DNA-bound dye.

Keywords: Binding; DNA; Heavy metals; Toxicity; Water.

Fig. 1

The chemical structure of DNA (left) and RNA (right). In double-stranded DNA, complementary base pairs bind via hydrogen bonds. Sugar phosphate backbones (grey) are aligned 3′ to 5′ in an anti-parallel fashion as shown. These sugars are deoxyribose and ribose in DNA and RNA, respectively. Furthermore, thymine is replaced by uracil in RNA, but both are capable of forming base pairs to adenine. Although RNA may form transient secondary structures that are double stranded, it is typically single-stranded. Copyright (2018) Nature Education

Fig. 2

Co-adenine complexes for (a) Co(II) and (b) Co(III). Copyright (2018) American Chemical Society

Fig. 3

Schematic representation of a complex binding model of Cu(II) to a GC BP in DNA. a Most probable first attachment site. b Complexing of Cu(II) between guanine and cytosine moieties. Copyright (2018) American Chemical Society

Fig. 4

Three pH-dependant Al complexes with DNA (Karlik et al. 1980). High pH and the formation of A1(OH)2+ is required for the formation of complex 1, which stabilises the dsDNA. In contrast, low pH values (~pH 3.5–5.5) promote Al(III) formation and binding to BPs (complex 2) which irreversibly destabilises, cross-links, and unwinds DNA in a manner similar to Hg(II) (Karlik et al. ; Macdonald and Martin ; Wu et al. 2005)

Fig. 5

Proposed complex II formation of Ag(I) to DNA whereby N-H~N hydrogen bonds of complementary BPs are converted into N–Ag–N bonds. In addition, such binding occurs independent of complex 1 formation. Copyright (2018) American Chemical Society

Fig. 6

Zn(II) cations bind phosphate groups which polarises the PO linkage to produce a positive dipole on the phosphorus atom. The formation of a ring with a 2′-hydroxyl group leads to cleavage of the phosphodiester linkage. It is postulated that other metal cations (e.g. Mn^2+, Co²⁺, Ni²⁺, Cu²⁺, La³⁺, Ce³⁺ and Lu³⁺) that depolymerize RNA can also bind via similar mechanisms. Copyright (2018) American Chemical Society

Fig. 7

Stereoscopic view of Ba(II) ion bis-coordination between G10 and G12 in crystals m⁵CGm⁵CGTG grown in the presence of Ba(II). G12 belongs to a symmetry-related helix and is shown in filled bonds. Copyright (2018) American Chemical Society