Sequence-Dependent Duplex Stabilization upon Formation of a Metal-Mediated Base Pair

• Published in: Chemistry : a European journal Vol. 22; no. 1; pp. 295 - 301
• Main Authors: Scharf, Philipp, Jash, Biswarup, Kuriappan, Jissy A., Waller, Mark P., Müller, Jens
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 04.01.2016; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Base metal; Base Pairing; Base pairs; bioinorganic chemistry; Chemical bonds; Chemistry; Chemistry, Multidisciplinary; Circular Dichroism; Deoxyribonucleic acid; DNA; DNA structure; DNA, B-Form - chemistry; Formations; Genes; Imidazole; Imidazoles - chemistry; Ligands; Mathematical analysis; Metals; Models, Molecular; Nucleosides; Oligonucleotides; Oligonucleotides - chemistry; Optimization; Organometallic Compounds - chemistry; phenanthroline; Phenanthrolines - chemistry; Physical Sciences; Quantum mechanics; quantum mechanics/molecular mechanics; Science & Technology; silver; Silver - chemistry; Stability; Stabilization; MOLECULAR CALCULATIONS; EFFECTIVE CORE POTENTIALS; NUCLEOSIDES; STABILITY; bioinorganic chemistry; IONS; quantum mechanics/molecular mechanics; DOUBLE HELIX; SIMULATION; NUCLEIC-ACIDS; DNA DUPLEXES; phenanthroline; FLUORESCENCE; DNA; silver
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201503405

An artificial nucleoside surrogate with 1H‐imidazo[4,5‐f][1,10]phenanthroline (P) acting as an aglycone has been introduced into DNA oligonucleotide duplexes. This nucleoside surrogate can act as a bidentate ligand, and so is useful in the context of metal‐mediated base pairs. Several duplexes involving a hetero base pair with an imidazole nucleoside have been investigated. The stability of DNA duplexes incorporating the respective AgI‐mediated base pairs strongly depends on the sequence context. Quantum mechanical/molecular mechanical (QM/MM) calculations have been performed in order to gain insight into the factors determining this sequence dependence. The results indicated that, in addition to the stabilizing effect that results from the formation of coordinative bonds, destabilizing effects may occur when the artificial base pair does not fit optimally into the surrounding B‐DNA duplex. Silver age: A strong effect of the neighboring base pairs and the next base pairs but one on the thermal stabilization induced by a novel metal‐mediated base pair has been observed (see graphic). This effect has been rationalized with the aid of quantum mechanical/molecular mechanical (QM/MM) calculations.