TY - JOUR
T1 - Ternary copper complexes for photocleavage of DNA by red light
T2 - Direct evidence for sulfur-to-copper charge transfer and d-d band involvement
AU - Dhar, Shanta
AU - Senapati, Dulal
AU - Das, Puspendu K.
AU - Chattopadhyay, Pabitra
AU - Nethaji, Munirathinam
AU - Chakravarty, Akhil R.
PY - 2003/10/8
Y1 - 2003/10/8
N2 - A new class of ternary copper(II) complexes of formulation [Cu(L n)B](ClO4) (1-4), where HLn is a NSO-donor Schiff base (HL1, HL2) and B is a NN-donor heterocyclic base viz. 1, 10-phenanthroline (phen) and 2,9-dimethyl-1,10-phenanthroline (dmp), are prepared, structurally characterized, and their DNA binding and photocleavage activities studied in the presence of red light. Ternary complex [Cu(L3)(phen)](ClO4) (5) containing an ONO-donor Schiff base and a binary complex [Cu(L2)2] (6) are also prepared and structurally characterized for mechanistic investigations of the DNA cleavage reactions. While 1-4 have a square pyramidal (4 + 1) CuN3OS coordination geometry with the Schiff base bonded at the equatorial sites, 5 has a square pyramidal (4 + 1) geometry with CuN3O2 coordination with the alcoholic oxygen at the axial site, and 6 has a square planar trans-CuN2O2 geometry, Binding of the complexes 1-4 to calf thymus DNA shows the relative order: phen ≫ dmp. Mechanistic investigations using distamycin reveal minor groove binding for the complexes. The phen complexes containing the Schiff base with a thiomethyl or thiophenyl moiety show red light induced photocleavage. The dmp complexes are essentially photonuclease inactive. Complexes 5 and 6 are cleavage inactive under similar photolytic conditions. A 10 μM solution of 1 displays a 72% cleavage of SC DNA (0.5 μg) on an exposure of 30 min using a 603 nm Nd: YAG pulsed laser (60 mJ/P) in Tris-HCl buffer (pH 7.2). Significant cleavage of 1 is also observed at 694 nm using a Ruby laser. Complex 1 is cleavage inactive under argon or nitrogen atmosphere. It shows a more enhanced cleavage in pure oxygen than in air. Enhancement of cleavage in D2O and inhibition with sodium azide addition indicate the possibility of the formation of singlet oxygen as a reactive intermediate leading to DNA cleavage. The d-d band excitation with red light shows significant enhancement of cleavage yield. The results indicate that the phen ligand is necessary for DNA binding of the complex. Both the sulfur-to-copper charge transfer band and copper d-d band excitations helped the DNA cleavage. While the absorption of a red photon induces a metal d-d transition, excitation at shorter visible wavelengths leads to the sulfur-to-copper charge transfer band excitation at the initial step of photocleavage. The excitation energy is subsequently transferred to ground state oxygen molecules to produce singlet oxygen that cleaves the DNA.
AB - A new class of ternary copper(II) complexes of formulation [Cu(L n)B](ClO4) (1-4), where HLn is a NSO-donor Schiff base (HL1, HL2) and B is a NN-donor heterocyclic base viz. 1, 10-phenanthroline (phen) and 2,9-dimethyl-1,10-phenanthroline (dmp), are prepared, structurally characterized, and their DNA binding and photocleavage activities studied in the presence of red light. Ternary complex [Cu(L3)(phen)](ClO4) (5) containing an ONO-donor Schiff base and a binary complex [Cu(L2)2] (6) are also prepared and structurally characterized for mechanistic investigations of the DNA cleavage reactions. While 1-4 have a square pyramidal (4 + 1) CuN3OS coordination geometry with the Schiff base bonded at the equatorial sites, 5 has a square pyramidal (4 + 1) geometry with CuN3O2 coordination with the alcoholic oxygen at the axial site, and 6 has a square planar trans-CuN2O2 geometry, Binding of the complexes 1-4 to calf thymus DNA shows the relative order: phen ≫ dmp. Mechanistic investigations using distamycin reveal minor groove binding for the complexes. The phen complexes containing the Schiff base with a thiomethyl or thiophenyl moiety show red light induced photocleavage. The dmp complexes are essentially photonuclease inactive. Complexes 5 and 6 are cleavage inactive under similar photolytic conditions. A 10 μM solution of 1 displays a 72% cleavage of SC DNA (0.5 μg) on an exposure of 30 min using a 603 nm Nd: YAG pulsed laser (60 mJ/P) in Tris-HCl buffer (pH 7.2). Significant cleavage of 1 is also observed at 694 nm using a Ruby laser. Complex 1 is cleavage inactive under argon or nitrogen atmosphere. It shows a more enhanced cleavage in pure oxygen than in air. Enhancement of cleavage in D2O and inhibition with sodium azide addition indicate the possibility of the formation of singlet oxygen as a reactive intermediate leading to DNA cleavage. The d-d band excitation with red light shows significant enhancement of cleavage yield. The results indicate that the phen ligand is necessary for DNA binding of the complex. Both the sulfur-to-copper charge transfer band and copper d-d band excitations helped the DNA cleavage. While the absorption of a red photon induces a metal d-d transition, excitation at shorter visible wavelengths leads to the sulfur-to-copper charge transfer band excitation at the initial step of photocleavage. The excitation energy is subsequently transferred to ground state oxygen molecules to produce singlet oxygen that cleaves the DNA.
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U2 - 10.1021/ja036681q
DO - 10.1021/ja036681q
M3 - Article
C2 - 14518998
AN - SCOPUS:0141992314
VL - 125
SP - 12118
EP - 12124
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 40
ER -