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Review
. 2024 Sep 13;29(18):4361.
doi: 10.3390/molecules29184361.

Metal-Based Drug-DNA Interactions and Analytical Determination Methods

Adriana Corina Hangan  1 , Luminița Simona Oprean  1 , Lucia Dican  2 , Lucia Maria Procopciuc  2 , Bogdan Sevastre  3 , Roxana Liana Lucaciu  4
Affiliations
Review

Metal-Based Drug-DNA Interactions and Analytical Determination Methods

Adriana Corina Hangan et al. Molecules. .

Abstract

DNA structure has many potential places where endogenous compounds and xenobiotics can bind. Therefore, xenobiotics bind along the sites of the nucleic acid with the aim of changing its structure, its genetic message, and, implicitly, its functions. Currently, there are several mechanisms known to be involved in DNA binding. These mechanisms are covalent and non-covalent interactions. The covalent interaction or metal base coordination is an irreversible binding and it is represented by an intra-/interstrand cross-link. The non-covalent interaction is generally a reversible binding and it is represented by intercalation between DNA base pairs, insertion, major and/or minor groove binding, and electrostatic interactions with the sugar phosphate DNA backbone. In the present review, we focus on the types of DNA-metal complex interactions (including some representative examples) and on presenting the methods currently used to study them.

Keywords: DNA; DNA interactions; bioinorganic chemistry; metal complexes.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The dogma of molecular biology [24].
Figure 2
Figure 2
DNA structure—simplified representation. Blue indicates the 5′-3′ phosphodiester bond and yellow indicates the deoxyribose phosphate backbone [28].
Figure 3
Figure 3
The double helix of DNA formed by hydrogen bonding between specific base pairs [30].
Figure 4
Figure 4
Common conformations adopted by DNA [36].
Figure 5
Figure 5
Metal-binding domains on nucleotides.
Figure 6
Figure 6
Non-covalent interaction of metal complexes with DNA. (1) A major groove binder, (2) a minor groove binder, (3) an electrostatic binding, and (4) an intercalator [50].
Figure 7
Figure 7
The major DNA–cisplatin adduct generating DNA deformation [58 modified].
Figure 8
Figure 8
Metal complex–DNA intercalation.
Figure 9
Figure 9
Metal complex–DNA insertion [68].
Figure 10
Figure 10
Hydrogen bonds between DNA nitrogenous bases.
Figure 11
Figure 11
Intercalative and groove binding modes of various chemicals to DNA [69].
Figure 12
Figure 12
Absorption spectra of complex [Cu(N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)-toluenesulfonamidate)(phenanthroline)] (20 μM) (in Tris-HCl/NaCl buffer) with increasing concentrations of calf thymus DNA. Insert shows the plot of [DNA]/(εa − εf) vs. [DNA].
Figure 13
Figure 13
Emission spectra of ethidium bromide bound to CT-DNA (λex = 500 nm, λem = 530–680 nm) in the absence and presence of 10, 20, 30, 40, 50, and 60 μM of [Cu(N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)-toluenesulfonamidate)(phenanthroline)].
Figure 14
Figure 14
Cyclic voltammograms of the (a) [Cu (7 amino -flavone)Cl2] and (b) [Ru(p-cymene)(6 aminochromone)Cl2] complexes [103].
Figure 15
Figure 15
Cleavage of the DNA molecule in the electrophoresis process [34].
Figure 16
Figure 16
Lambda DNA/EcoRI+HindIII marker [34].
Figure 17
Figure 17
Electroferogram in agarose gel of the pUC18 plasmid treated with the [Cu(N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)-toluenesulfonamidate)2(phenanthroline)(H2O)] complex. (1) Base marker; (2) control; (3) control with reducing agents; (4) CuSO4·5H2O 6 μM; (5) CuSO4·5H2O 12 μM; (6) CuSO4·5H2O 18 μM; (7) CuSO4·5H2O 24 μM; (8) CuSO4·5H2O 30 μM; (9) complex 6 μM; (10) complex 12 μM; (11) complex 18 μM; (12) complex 24 μM; and (13) complex 30 μM [131].
Figure 18
Figure 18
Electroferogram in agarose gel of the pUC18 plasmid treated with the [Cu(N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)-toluenesulfonamidate)2(phenanthroline)(H2O)] complex and various inhibiting agents. (1) Base marker; (2) control; (3) control with reducing agents; (4) complex 15 μM without inhibitors; (5) complex 15 μM + DMSO; (6) complex 15 μM + t-butyl alcohol; (7) complex 15 μM + NaN3; (8) complex 15 μM + piperidone; (9) complex 15 μM + distamycin; (10) complex 15 μM + SOD; and (11) complex 15 μM + neocuproine [131].
Figure 19
Figure 19
CT-DNA melting curves in the presence of 20 μM complex (red) and in its absence (blue). [Cu(N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)-toluenesulfonamidate)(phenanthroline)] in cacodylate buffer 1 mM at pH 8.0, DNA:complex = 2.5:1.
Figure 20
Figure 20
The influence of Cu2+ complexes on the viscosity of a DNA solution: blue—[Cu(NST)2(phenanthroline)]: intercalation; red—[Cu(NST)2(NH3)2]·H2O: minor/major groove interactions; green—[Cu(phenanthroline)2]2+: partial intercalation; and black—CuCl2: standard NST = N-2-(4,5-dimetylthyazol)naphtalenesulfonamide [139].
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