Pentanuclear Platinum(<scp>II</scp>) Macrocycles with Nucleobases

Rauterkus, Michael J.; Krebs, Bernt

doi:10.1002/anie.200352950

Cited by 17 publications

(2 citation statements)

References 25 publications

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“…The binding of positively charged transition metal complexes to DNA seems to be a promising mechanism as a basis for the rational design of novel anticancer drugs. − Principally, there are several potential binding sites in DNA for metal ions. While the nucleobases of DNA are the target for intercalation − and covalent binding in current research, − the phosphate diesters of the DNA backbone are not considered to form strong bonds with metal ions. − Complexes that bind by hydrogen bonds to the phosphate diesters have been developed. − Instead, we intended to target the phosphate diester groups of the DNA backbone by covalent binding to develop a new family of cytotoxic complexes as potential anticancer drugs. − Although the hydrolytic cleaving activity of enzymes as phosphatases or nucleases and their model complexes indicates a certain binding affinity of transition metal ions for phosphate esters, − we intended to increase the binding strength by molecular recognition of two neighboring phosphate diesters of the DNA backbone in accordance with the multivalence principle . In this respect, we performed a rational design for a family of dinuclear transition metal complexes to bind preferentially to two neighboring phosphate diesters of the DNA backbone and not by binding to the nucleobases (Figure a) .…”

Section: Introductionmentioning

confidence: 99%

Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes

et al. 2020

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Cytostatic metallo-drugs mostly bind to the nucleobases of DNA. A new family of dinuclear transition metal complexes was rationally designed to selectively target the phosphate diesters of the DNA backbone by covalent bonding. The synthesis and characterization of the first dinuclear NiII 2 complex of this family are presented, and its DNA binding and interference with DNA synthesis in polymerase chain reaction (PCR) are investigated and compared to those of the analogous CuII 2 complex. The NiII 2 complex also binds to DNA but forms fewer intermolecular DNA cross-links, while it interferes with DNA synthesis in PCR at lower concentrations than CuII 2. To simulate possible competing phosphate-based ligands in vivo, these effects have been studied for both complexes with 100–200-fold excesses of phosphate and ATP, which provided no disturbance. The cytotoxicity of both complexes has been studied for human cancer cells and human stem cells with similar rates of proliferation. CuII 2 shows the lowest IC50 values and a remarkable preference for killing the cancer cells. Three different assays show that the CuII 2 complex induces apoptosis in cancer cells. These results are discussed to gain insight into the mechanisms of action and demonstrate the potential of this family of dinuclear complexes as anticancer drugs acting by a new binding target.

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Section: Introductionmentioning

confidence: 99%

Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes

et al. 2020

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“…[1][2][3] Cyclic compounds of Pt(II) and Pd(II) were some of the first metals investigated because their square planar geometry provides corners for the formation of complex shapes. [4][5][6][7] Geometries include trimers, tetramers (molecular squares), pentamers, and hexamers 4,6,[8][9][10] as well as a few higher n-mers. 11 Typically these are held together by bridging N donor ligands.…”

Section: Introductionmentioning

confidence: 99%

Cyclic Tetranuclear and Hexanuclear Palladium(II) Complexes and Their Host−guest Chemistry

et al. 2007

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Cyclic tetrameric complexes have been prepared by the reaction of Pd(en)Cl 2 or Pd(dapol)Cl 2 , or their nitrato analogs, with Na 2 (5′GMP) in aqueous solution, where en = 1,2-diaminoethane, dapol = 1,3-diamino-2-propanol, 5′-GMP = guanosine 5′-monophosphate. Addition of certain small molecules containing hydrophobic groups resulted in the expansion of the tetramer to a cyclic hexamer with strong bonding of one guest per hexameric host. At pH 5-6, the guest molecule can be a cation, anion, or neutral, and those species containing trimetylsilyl and t-butyl groups bonded the most strongly. The size of the central cavity of the [Pd(en)(5′GMP)] 6 host has been estimated to be 5.2 Ǻ. Formation of the host-guest complex caused a large upfield shift (Δδ) of 2.5-2.9 ppm in the 1 H NMR spectrum of the most highly affected guest protons, which were those in closest proximity to the guanine nucleobases. NOESY spectra were used to determine the interaction sites between the host and the guest. Apparent association constants determined at 26 °C and pD 5.4 for the [Pd(en)(5′GMP)] 6 -DSS and [Pd(en)(5′GMP)] 6 -t-butanol systems, where DSS is 3-(trimethylsilyl)-1-propanesulfonate anion, were 1.36 ± 0.11 × 10 4 and 2.74 ± 0.95 × 10 4 M −3/2 , respectively. The Pd(dapol)-5′GMP system forms hexameric host-guest complexes, similar in nature to those of the Pd(en)-5′-GMP system. The molecular and crystal structures of Pd(dapol)Cl 2 are also reported.

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Design, Synthesis, and Characterization of 0‐D, 1‐D, and 2‐D Zinc–Adeninate Coordination Assemblies

Geib

Kim

2015

Bulletin Korean Chem Soc

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Synthesizing structurally well-defined materials via coordination-directed molecular assembly has attracted and challenged chemists and material scientists alike. Biomolecules are fascinating materials as building blocks for constructing coordination polymers for several reasons: they are likely biocompatible as they exist naturally in biological systems; they often have versatile metal coordination modes; and they display molecular recognition and self-assembly inclinations that could, in the end, translate into exciting material properties. 1,2 Metal-biomolecule coordination chemistry is potentially useful for building crystalline solid-state materials that might show interesting structures and properties. [3][4][5][6][7][8][9][10][11] In this study, we demonstrate the synthesis and characterization of zincadeninate coordination polymers with 0-D, 1-D, and 2-D structures. We describe methods for controlling the structure of these materials by applying different synthetic conditions and discuss their structural relationships.Adenine is a good candidate biomolecule for building coordination polymers via molecular assembly because it is small, rigid, and has multiple metal coordination sites. 1 While studying the coordination chemistry between adenine and metal ions, several interesting coordination patterns have been discovered. 12-20 One of the less common metal-adenine coordination modes is restricting metal coordination to N7 and N9 sites of adeninate while leaving N1 and the amino group uncoordinated to participate in hydrogen bonding, which can lead to hierarchically assembled structures ( Figure 1). 18,[21][22][23] To understand this coordination mode further, we explored the syntheses in which a mixture of adenine and zinc salts in dimethylformamide (DMF) and pyridine was prepared together and run under various conditions. As a result, we were able to prepare 0-D, 1-D, and 2-D coordination polymers with the same coordination mode.A discrete macrocycle (0-D) was synthesized and characterized. 18 A crystalline material, (Zn 6 (ad) 6 (py) 6 (dimethylcarbamate) 6 ) (ad = adeninate; py = pyridine), was prepared via a solvothermal reaction at 140 C for 24 h between adenine and zinc nitrate hexahydrate in DMF and pyridine. Single crystal X-ray diffraction data revealed that the macrocycle is composed of six adeninates and six Zn 2+ cations. Each Zn 2+ is bound to either the N7 or N9 position of two different adeninates. The imidazole rings of the adeninates bridge the Zn 2+ centers. In addition, each Zn 2+ is coordinated to a single carbamate anion and a single pyridine, which complete the tetrahedral coordination sphere ( Figure 2). The carbamate anion is formed in situ from the thermal decomposition of DMF. 24 The N7 and N9 of adeninate coordinate to the Zn 2+ , leaving N1 and the amino group available for hydrogen bonding. As a result, the cooperative adeninate-adeninate hydrogen bonding interactions induce self-assembly of macrocycles into an extended structure. Approximately 10.5 DMF molecules per macrocycle...

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Pentanuclear Platinum(II) Macrocycles with Nucleobases

Cited by 17 publications

References 25 publications

Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes

Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes

Cyclic Tetranuclear and Hexanuclear Palladium(II) Complexes and Their Host−guest Chemistry

Design, Synthesis, and Characterization of 0‐D, 1‐D, and 2‐D Zinc–Adeninate Coordination Assemblies

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