Methylmercury(II) binding to single-stranded and duplex DNA: complexes formed are distinguishable by optical detection of magnetic resonance spectroscopy.

Abstract

Binding of CH3Hg(II) to duplex and singlestranded calf thymus DNA leads to an external heavy atom effect that is associated with the formation ofcomplexes directly with the purine and pyrimidine bases. When CH3Hg(II) is added at a concentration insufficient to cause denaturation, clearly distinguishable optical detection of magnetic resonance spectra are observed from the duplex and single-stranded DNA complexes. Comparison of the dominant signals with those observed from CH3Hg(II) complexes of model mononucleotides and mononucleosides allows their identification as guanine complexed at N7 in the duplex sample and thymine complexed at N3 in the single-stranded sample. On the basis of these measurements, it is estimated that this experiment presently is capable of detecting about 2% singlestranded DNA in a sample made up predominantly of the duplex structure. Methylmercury, CH3Hg(II), is known to bind to the bases of DNA (1, 2). When added at sufficient concentration, which depends upon such factors as temperature, base composition, and the pH and ionic strength of the buffer, CH3Hg(II) causes denaturation of duplex DNA (3,4). CH3Hg(II) binds more strongly to N than to 0 atoms and coordinates tightly with only one ligand; thus, unlike Ag(I), which binds to two ligands in linear coordination, CH3Hg(II) is not expected to crosslink DNA bases. At pH near 7, CH3Hg(II) coordinates most strongly at. the N3 site of thymine and somewhat less tightly at the N1 site ofguanine (1, 3). These atoms are involved in Watson-Crick base pairing of the DNA duplex and thus are not accessible to complexing with CHjHg(II) in the absence of disruption of the base pairing. The coordination chemistry of CH3Hg(II) is consistent, therefore, with the observation (3, 4) that while singlestranded DNA binds CH3Hg(II) noncooperatively at low CH3Hg(II) concentrations, no complexing with duplex DNA is observed until a critical concentration is reached, whereupon massive binding occurs cooperatively, accompanied by denaturation of the DNA. Ag(I), on the other hand, forms complexes at very low concentrations with duplex DNA in the absence of denaturation (5, 6). Release ofprotons that accompanies binding suggests that Ag(I) may replace protons in the base pairs and form linear complexes between complementary bases.We have recently studied-(7) the complexes formed by CH3Hg(II) with duplex calf thymus DNA (CT-DNA), using optical detection of triplet state magnetic resonance (ODMR) spectroscopy. Complexes were formed by equilibrium dialysis at CH3Hg(II) concentrations insufficient to cause denaturation. In this application of ODMR we were able to take advantage of the heavy atom effect (8) induced by the Hg atom to selectively detect ODMR signals from complexed bases. ComparisonThe publication costs of-this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.ofthe ODMR spectra with those of CH3Hg(II).mononucleotide ...

Helical Assembly of Flavin Mononucleotides on Carbon Nanotubes as Multimodal Near-IR Hg(II)-Selective Probes

“…Also, addition of Hg 2+ to a 1 μM solution of FMN causes a linear decrease in I PL with increasing Hg 2+ concentration (the red trace of Figure e), whereas addition of this metal ion to a 10 μM FMN solution results in an exponential decrease in the PL intensity. Moreover, the fact that addition of a 10-fold excess of Hg 2+ , which should promote predominant formation of the 1:1 complex, does not completely quench the PL of FMN suggests that, along with chemical bonding with FMN, Hg 2+ might be involved in modulation of the aggregation state of FMN. , Hg­(II) is known to bind with bases of DNA and RNA, resulting in quenching of nucleotide PL owing to the heavy-atom effect . This is the primary reason for quenching of FMN PL.…”

“…Moreover, the fact that addition of a 10-fold excess of Hg 2+ , which should promote predominant formation of the 1:1 complex, does not completely quench the PL of FMN suggests that, along with chemical bonding with FMN, Hg 2+ might be involved in modulation of the aggregation state of FMN. 48,49 Hg(II) is known to bind with bases of DNA and RNA, 50 resulting in quenching of nucleotide PL owing to the heavy-atom effect. 51 This is the primary reason for quenching of FMN PL.…”

DNA fragments assembled on polyamidoamine‐grafted core‐shell magnetic silica nanoparticles for removal of mercury(II) and methylmercury(I)

“…Higher generation PAMAMs possessed more primary amine groups on the surfaces available for DNA immobilization, and hence enhanced removal capacities and efficiencies were expected. Regarding MeHg(I), however, it coordinated most strongly at the N3 site of thymine and somewhat less tightly at the N1 site of guanine, which were involved in Watson‐Crick base pairing of the DNA duplex. Therefore, coordination between MeHg(I) and normal‐structured DNA duplex was theoretically not very strong.…”

Permeation thresholds for hydrophilic small biomolecules across microvascular and epithelial barriers are predictable on basis of conserved biophysical properties

“…In support of these conclusions, at the in vivo morphologic studies of Moller-Madsen ( 1990 , 1991 ) in which it is shown that CH3Hg+ deposits extensively throughout the CNS of rodents after administration via intraperitoneal and oral routes. It can be postulated that, upon permeation of barriers, the final common pathway underlying the mechanism of intracellular CH3Hg+ toxicity is genotoxicity (Grotto et al 2009 ) due to its covalent binding of DNA (Maki and Ott 1981 ) and disruption of transcription pathways, leading to cellular instability and cell death. Exposure to significant doses of CH3Hg+ during pregnancy have resulted in offspring with significant neurodevelopmental abnormalities as was the case at Minamata Bay (Eto et al 2010 ).…”