1. Metal Complexes as DNA
Intercalators
HONG-KE LIU &PETER J. SADLER
Fatemeh Babaei
Intercalation induces structural distortions

2. Ethidium intercalated between
two adenine-thymine base pairs
These molecules cause structural modifications that can lead to functional changes, often
to inhibition of transcription and replication and DNA repair processes, which make
intercalators 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 major
That 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 containing
aromatic fragments can bind to DNA
by intercalation without direct metal
coordination 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 DNA
Metallo intercalation
Metallo insertion

6. Intercalation by Dual-Function Metal Complexes with σ-Bonded Side Arm Intercalators
When do the Dual function happen?
When the aromatic side arms or arene
ligands can intercalate between DNA
bases while the metal coordinates
directly 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 cGMP
Arene Rate of reaction
( 10-2 M-1 S-1)
Tetrahydroantheracene 14.72
biphenyl 8.06
Dihydroanthracene 7.08
P-Cymene 2.49
Benzen 1.13
 Cytotoxic activity
Arene IC50 (μM)
Tetrahydroantheracene 0.5
Dihydroanthracene 2 P-cymene(cym) Dihydroanthracene(dha)
Biphenyl 5
P-Cymene 10 Benzen (ben)
Benzen 17
Cytotoxic activity, conformational distortions, recognation by DNA-binding proteins, and repair
mechanisms are depend on the Arene.

9. Adducts of Ru-Arene Complexes with Nucleobases and DNA
Large low-field shifts for protons on rings B and C of Ru-tha are observed for the monoruthenated DNA adduct.

11. Thanks for your attention
Eram Garden (Shiraz)

12. Qazvin
Tehran
Tehran
Esfahan
Shiraz
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