organometallic chemistry

Intercalation induces structural distortions

Metal Complexes as DNA

Intercalators

HONG-KE LIU &PETER J. SADLER

Fatemeh Babaei

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.

Two major modes of inercalation

Classical intercalation Threading intercalation

Inserted between GpG base pair

That form the top and the bottom of

intercalation site

Occupy and interact with both major

and minor grooves of DNA

benzo[α]pyrene

acridine-4-carboxamides

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.

Interaction of Metallointercalators with DNA

Metallo intercalationMetallo insertion

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.

Intercalation by Dual-Function Metal Complexes with σ-Bonded Side Arm Intercalators

N7

Increasing the cytotoxicity by

adding pyridine and quinoline

Using as an anticancer drug

pyridine and quinoline have

intercalation with DNA duplex

Dihydroanthracene(dha)P-cymene(cym)

Benzen (ben)

Intercalation by Organometallic Ru -Arene Complexes

Dihydroanthracene(dha)P-cymene(cym)

Benzen (ben)

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

Rate of reaction of (η6-arene)Ru- (en)(H2O]2+

with cGMP

Arene IC50 (μM)

Tetrahydroantheracene 0.5

Dihydroanthracene 2

Biphenyl 5

P-Cymene 10

Benzen 17

Cytotoxic activity

Cytotoxic activity, conformational distortions, recognation by DNA-binding proteins, and repair

mechanisms are depend on the Arene.

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.

Eram Garden (Shiraz)

Thanks for your attention

Qazvin

Tehran

Tehran

Shiraz

Esfahan

Shiraz