A conformationally flexible dinuclear Pt^II complex with differential behavior of its two states toward quadruplex DNA

TY - JOUR

T1 - A conformationally flexible dinuclear PtII complex with differential behavior of its two states toward quadruplex DNA

AU - Von Grebe, Philipp

AU - Suntharalingam, Kogularamanan

AU - Vilar, Ramon

AU - Sanz Miguel, Pablo J.

AU - Herres-Pawlis, Sonja

AU - Lippert, Bernhard

PY - 2013/8/19

Y1 - 2013/8/19

N2 - The reaction of tetrakis(pyridine-2-yl)pyrazine (tppz) with 2 equiv of (2,2′-bpy)PtII in water yields two isomeric dinuclear cations, [{Pt(2,2′-bpy)}2(tppz)]4+, in which Pt coordination exclusively takes place through the two pairs of pyridine-2-yl nitrogen atoms. The two conformational isomers differ in their overall shape, with the formation of "Z" and "U" shapes, which are formed at 40°C (Z isomer, 1) and under reflux conditions (U isomer, 2), respectively. X-ray crystal-structure analyses of the Z isomer, [{Pt(2,2′-bpy)} 2(tppz)](PF6)4×3 CHCl3×4 H2O (1 a), and of the U isomer, [{Pt(2,2′-bpy)} 2](PF6)4×2 CH3CN×1.5 H2O (2 a), were carried out. Co-crystallization of compound 2 with PtCl2(2,2′-bpy) yielded [{Pt(2,2′-bpy)} 2(tppz)](BF4)4×[PtCl2(2, 2′-bpy)]×4.5 H2O (3), in which the PtCl 2(2,2′-bpy) entity was sandwiched between the two 2,2′-bpy faces of the U-shaped cation (2). Quantum chemical calculations revealed that the U isomer was more stable than the Z isomer, both in the gas phase and in an aqueous environment. These two isomers display different affinities toward duplex DNA and human telomeric quadruplex DNA (Htelo), as concluded from CD spectroscopy and FID assays. Thus, the U isomer binds significantly more strongly to quadruplex DNA (DC50=0.38 μM) than the Z isomer (DC50=8.50 μM).

AB - The reaction of tetrakis(pyridine-2-yl)pyrazine (tppz) with 2 equiv of (2,2′-bpy)PtII in water yields two isomeric dinuclear cations, [{Pt(2,2′-bpy)}2(tppz)]4+, in which Pt coordination exclusively takes place through the two pairs of pyridine-2-yl nitrogen atoms. The two conformational isomers differ in their overall shape, with the formation of "Z" and "U" shapes, which are formed at 40°C (Z isomer, 1) and under reflux conditions (U isomer, 2), respectively. X-ray crystal-structure analyses of the Z isomer, [{Pt(2,2′-bpy)} 2(tppz)](PF6)4×3 CHCl3×4 H2O (1 a), and of the U isomer, [{Pt(2,2′-bpy)} 2](PF6)4×2 CH3CN×1.5 H2O (2 a), were carried out. Co-crystallization of compound 2 with PtCl2(2,2′-bpy) yielded [{Pt(2,2′-bpy)} 2(tppz)](BF4)4×[PtCl2(2, 2′-bpy)]×4.5 H2O (3), in which the PtCl 2(2,2′-bpy) entity was sandwiched between the two 2,2′-bpy faces of the U-shaped cation (2). Quantum chemical calculations revealed that the U isomer was more stable than the Z isomer, both in the gas phase and in an aqueous environment. These two isomers display different affinities toward duplex DNA and human telomeric quadruplex DNA (Htelo), as concluded from CD spectroscopy and FID assays. Thus, the U isomer binds significantly more strongly to quadruplex DNA (DC50=0.38 μM) than the Z isomer (DC50=8.50 μM).

KW - conformation analysis

KW - coordination modes

KW - DNA

KW - molecular tweezers

KW - platinum

UR - http://www.scopus.com/inward/record.url?scp=84882264946&partnerID=8YFLogxK

U2 - 10.1002/chem.201301400

DO - 10.1002/chem.201301400

M3 - Article

C2 - 23852779

AN - SCOPUS:84882264946

SN - 0947-6539

VL - 19

SP - 11429

EP - 11438

JO - Chemistry (Weinheim an der Bergstrasse, Germany)

JF - Chemistry (Weinheim an der Bergstrasse, Germany)

IS - 34

ER -