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Organometallic chemistry
Organometallic chemistry
Organometallic chemistry
Organometallic chemistry
Organometallic chemistry
Organometallic chemistry
Organometallic chemistry
Organometallic chemistry
Organometallic chemistry
Organometallic chemistry
Organometallic chemistry
Organometallic chemistry
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Organometallic chemistry

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  • 1. Metal Complexes as DNA Intercalators HONG-KE LIU &PETER J. SADLER Fatemeh BabaeiIntercalation induces structural distortions
  • 2. Ethidium intercalated between two adenine-thymine base pairsThese molecules cause structural modifications that can lead to functional changes, oftento inhibition of transcription and replication and DNA repair processes, which makeintercalators potent mutagens.
  • 3. Two major modes of inercalation Classical intercalation Threading intercalation benzo[α]pyrene acridine-4-carboxamides Inserted between GpG base pair Occupy and interact with both majorThat form the top and the bottom of and minor grooves of DNA intercalation site
  • 4. Intercalation by Inert Square-Planar and Octahedral Metal ComplexesSquare-planar complexes containingaromatic fragments can bind to DNAby intercalation without direct metalcoordination to DNA bases. Octahedral metallointercalators permit the targeting of specific DNA sites by matching the shape, symmetry, and functionalities of the metal complex to that of the DNA target.
  • 5. Interaction of Metallointercalators with DNAMetallo intercalation Metallo insertion
  • 6. Intercalation by Dual-Function Metal Complexes with σ-Bonded Side Arm IntercalatorsWhen do the Dual function happen?When the aromatic side arms or areneligands can intercalate between DNAbases while the metal coordinatesdirectly to a DNA base.N7 Increasing the cytotoxicity by adding pyridine and quinoline Using as an anticancer drug  pyridine and quinoline have intercalation with DNA duplex
  • 7. Intercalation by Organometallic Ru -Arene Complexes P-cymene(cym) Dihydroanthracene(dha) Benzen (ben)
  • 8.  Rate of reaction of (η6-arene)Ru- (en)(H2O]2+with cGMPArene Rate of reaction ( 10-2 M-1 S-1)Tetrahydroantheracene 14.72biphenyl 8.06Dihydroanthracene 7.08P-Cymene 2.49Benzen 1.13 Cytotoxic activityArene IC50 (μM)Tetrahydroantheracene 0.5Dihydroanthracene 2 P-cymene(cym) Dihydroanthracene(dha)Biphenyl 5P-Cymene 10 Benzen (ben)Benzen 17Cytotoxic activity, conformational distortions, recognation by DNA-binding proteins, and repairmechanisms are depend on the Arene.
  • 9. Adducts of Ru-Arene Complexes with Nucleobases and DNALarge low-field shifts for protons on rings B and C of Ru-tha are observed for the monoruthenated DNA adduct.
  • 10. Thanks for your attentionEram Garden (Shiraz)
  • 11. Qazvin Tehran Tehran EsfahanShiraz Shiraz

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