CHEM3910 Lecture Notes - Lecture 5: Cisplatin, Nucleophile, Guanine
5 Jul 2018
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CHEM3910 Biomolecules 460381099
PART 1
Section 6
Metal DNA Chemistry: Utilizes metal nucleic acid chemistry whereby metal-DNA can interact
through:
• Coordination: interaction of ‘soft’ metal ion with nucleophilic N-donor atoms of bases, forming
strong covalent bonds as a result. As already stated, the N7 atom of guanine and adenine in the
major groove is particularly nucleophilic. Example: coordination of soft metals (i.e. cis-platin) to
two adjacent guanine N7 bases on the same strand of DNA, known as intrastrand cross-link.
Interstrand cross-link can also occur, at a lesser degree, at the N3 position of cytosine. Hard
metals are able to coordinate to the oxygen atoms of the DNA backbone. Thus, hard metals
coordinate to the phosphate backbone while soft metals coordinate to the nucleobases.
• Intercalation: non-covalent interaction between saturated ligands. Metallo-intercalation: planar
aromatic ligands stack between base pairs of DNA. These are stabilised by dipole-dipole forces
and electrostatic interactions. H-bonding intercalation: H-bonding occurs between complex and
DNA. This occurs with DNA phosphate O groups and NH3 of purine bases.
• Redox-cleavage: in particular the Fenton reaction, uses iron and hydrogen peroxide to form OH
radicals. These radicals pull H atom off sugar, allow DNA scission at the ribose sugar ring and
sugar-phosphate backbone.
• Hydrolytic cleavage: these are milder than redox reactions and do not degrade sugar or base.
Restriction enzymes are used in this process. Metal ion acts as a Lewis acid, weakening the
phosphate-oxygen bonds of backbone. This makes it more susceptible to reactions with water,
as water acts as the nucleophile.
Document Summary
Metal dna chemistry: utilizes metal nucleic acid chemistry whereby metal-dna can interact through: coordination: i(cid:374)teractio(cid:374) of (cid:858)soft(cid:859) (cid:373)etal io(cid:374) with (cid:374)ucleophilic n-donor atoms of bases, forming strong covalent bonds as a result. As already stated, the n7 atom of guanine and adenine in the major groove is particularly nucleophilic. Example: coordination of soft metals (i. e. cis-platin) to two adjacent guanine n7 bases on the same strand of dna, known as intrastrand cross-link. Interstrand cross-link can also occur, at a lesser degree, at the n3 position of cytosine. Hard metals are able to coordinate to the oxygen atoms of the dna backbone. Thus, hard metals coordinate to the phosphate backbone while soft metals coordinate to the nucleobases. Metallo-intercalation: planar aromatic ligands stack between base pairs of dna. These are stabilised by dipole-dipole forces and electrostatic interactions.
