Paul de Hoog

New polydentate and polynucleating N-donor ligands from amines and 2,4,6-trichloro-1,3,5-triazine

An efficient synthesis of a novel class of multidentate polynucleating ligands has been developed based on high-yielding chloride substitutions of 2,4,6-trichloro-1,3,5-triazine by primary and secondary amines.

An unprecedented 1D ladder coordination polymer based on a pentanuclear copper(ii) 2,4,6-tris(dipyridin-2-ylamino)-1,3,5-triazine building blockElectronic supplementary information (ESI) available: additional characterization data for 1 (µeff vs. T and B curves), TGA, XRD. See http://www.rsc.org/suppdata/cc/b2/b203394a/

Copper(II) nitrate reacts with the rigid polydentate triple-connecting dpyatriz ligand in acetonitrile to an unprecedented infinite molecular ladder in which five-coordinated copper pseudo-dimer are bridged by nitrate anions and the coordination polymer chains are linked by hexacoordinated copper ions leading to the formation of large guest cavities.

Copper−1,10-Phenanthroline Complexes Binding to DNA: Structural Predictions from Molecular Simulations

Copper-1,10-phenanthroline (phen) complexes Cu(phen)(2)(), Cu(2-Clip-phen), and Cu(3-Clip-phen) (Clip = a serinol bridge between the phen parts) are typically employed as DNA-cleaving agents and are now becoming increasingly important for building multifunctional drugs with improved cytotoxic properties. For instance, Cu(3-Clip-phen) has been combined with distamycin-like minor-groove binders and cisplatin-derivatives, leading to promising results. Density Functional Theory (DFT) and docking calculations as well as molecular dynamics (MD) simulations were performed to describe the mode of binding to DNA of these complexes. Our data suggest the minor-groove binding to be more probable than (partial) intercalation and major-groove binding. In addition, it was found that a combination of factors including planarity, van der Waals interactions with DNA, and structural complementarities may be the key for the cleavage efficiency of these copper complexes.

Coordination compounds from 1,3,5-triazine-derived multi-directional ligands: application in oxidation catalysis.

Abstract A series of 1,3,5-triazine- and 2,2′-dipyridylamine-based ligands have been prepared and the crystal structure from one of them was solved. The coordination of these dendritic multi-directional ligands with various metal salts led to attractive supramolecular architectures. In particular, an unprecedented 1D ladder coordination polymer resulted from the reaction of copper(II) nitrate and 2b. Reaction of nickel(II) perchlorate with 2b led to the formation of a new dinuclear nickel complex for which the crystal structure is discussed. Finally, the polynucleating ligands 2b–2e were used with copper(II) nitrate to catalyze the oxidation of 3,5-di-tert-butylcatechol. The best catalytic system was obtained when the first-generation dendrimer 2e was employed as a ligand for Cu(II), showing that the stability of the catalyst could be improved by incorporating 2,2′-dipyridylamine into a dendritic material.

Platinated Copper(3‐Clip‐Phen) Complexes as Effective DNA‐Cleaving and Cytotoxic Agents

The synthesis and biological activity of three heteronuclear platinum-copper complexes based on 3-Clip-Phen are reported. These rigid complexes have been designed to alter the intrinsic mechanism of action of both the platinum moiety and the Cu(3-Clip-Phen) unit. The platinum centers of two of these complexes are coordinated to a 3-Clip-Phen moiety, an ammine ligand and two chlorides, which are either cis or trans to each other. The third complex comprises two 3-Clip-Phen units and two chloride ligands bound in a trans fashion to the platinum ion. DNA-cleavage experiments show that the complexes are highly efficient nuclease agents. In addition, a markedly difference in their aptitude to perform direct double-strand cleavage is observed, which appears to be strongly related to the ability of the platinum unit to coordinate to DNA. Indeed, complex 6 is unable to coordinate to DNA, which is reflected by its incapability to carry out double-strand breaks. Nonetheless, this complex exhibits efficient DNA-cleavage activity, and its cytotoxicity is high for several cell lines. Complex 6 shows better antiproliferate activity than both cisplatin and Cu(3-Clip-Phen) toward most cancer cell lines. Furthermore, the cytotoxicity observed for 1 is for most cell lines close to that of cisplatin, or even better. Cu(3-Clip-Phen) induces very low cytotoxic effects, but a marked migratory activity. Complex 6 presents DNA-cleavage properties comparable to the one of Cu(3-Clip-Phen), but it does not show any migratory activity. Interestingly, both Cu(3-Clip-Phen) and 6 induces vacuolisation processes in the cell in contrast to complex 1 and cisplatin. Thus, the four complexes cisplatin tested, Cu(3-Clip-Phen), 1 and 6 stimulate different cellular responses.

The new multi-directional polydentate ligand 2,4,6-(di-pyridin-2-yl-amino)-(1,3,5)triazine (dpyatriz) can discriminate between Zn(II) and Co(II) nitrate

Abstract The rigid multidentate tri-directional and potentially nonadentate ligand 2,4,6-(di-pyridin-2-yl-amino)-[1,3,5]triazine (dpyatriz) is able to differentiate between Co(II) and Zn(II) nitrate. With Co(II) nitrate, a dinuclear [Co2(dpyatriz)2(NO3)2(MeOH)2](NO3)2(MeOH)2 complex is formed. Dpyatriz acts as a tetradentate (bisdidentate) ligand, with the octahedral coordination completed by a MeOH molecule and a monodentate nitrate anion. With Zn(II) nitrate, dpyatriz acts as an hexadentate ligand (trisdidentate), where each ligand binds to three Zn ions. Two of the Zn ions are five coordinated in a ZnO3N2 chromophore (the trigonal bipyramidal geometry is completed by two monodentate nitrato ligands). The other two Zn ions are hexacoordinated in a ZnN4O2 chromophore, formed by four pyridine-type ligands and a chelating, didentate nitrato ligand. The molecular structure of the free ligand has also been determined using XRD. For the Zn and Co complexes, the IR and IR+UV spectra, are reported as well.

DNA cleavage and binding selectivity of a heterodinuclear Pt–Cu(3-Clip-Phen) complex

The synthesis and nuclease activity of a new bifunctional heterodinuclear platinum–copper complex are reported. The design of this ditopic coordination compound is based on the specific mode of action of each component, namely, cisplatin and Cu(3-Clip-Phen), where 3-Clip-Phen is 1-(1,10-phenanthrolin-3-yloxy)-3-(1,10-phenanthrolin-8-yloxy)propan-2-amine. Cisplatin is not only able to direct the Cu(3-Clip-Phen) part to the GG or AG site, but also acts as a kinetically inert DNA anchor. The nuclease activity of this complex has been investigated on supercoiled DNA. The dinuclear compound is not only more active than Cu(3-Clip-Phen), but is also capable of inducing direct double-strand breaks. The sequence selectivity of the mononuclear platinum complex has been investigated by primer extension experiments, which reveal that its interaction with DNA occurs at the same sites as for cisplatin. The Taq polymerase recognizes the resulting DNA damage as different from that for unmodified cisplatin. The sequence-selective cleavage has been investigated by high-resolution gel electrophoresis on a 36-bp DNA fragment. Sequence-selective cleavages are observed in the close proximity of the platinum sites for the strand exhibiting the preferential platinum binding sites. The platinum moiety also coordinates to the other DNA strand, most likely leading only to mono guanine or adenine adducts.

Novel zigzag 1D coordination polymer from copper(II) chloride and N,N′-{2,4-di[(di-pyridin-2-yl)amine]-1,3,5-triazine}ethylenediamine exhibiting ferromagnetic interactions

Copper(II) chloride reacts with the polydentate 1,3,5-triazine containing ligand opytrizediam in methanol–THF to form a unique infinite zigzag coordination polymer in which trinuclear copper complexes are bridged by chloride anions, giving rise to five-coordinated ferromagnetically coupled copper pseudo-dimers.

Metal-mediated transformation of a triazinephenanthridinium ligand leading to a {Pd5} coordination complex observed crystallographically and by cryospray mass spectrometry.

The formation of a pentanuclear palladium(II) complex with a phenanthridinonetriazine-based ligand system, which itself is formed by a metal-mediated rearrangement of a triazinephenanthridinium proligand, is described.

Novel heteronuclear ruthenium–copper coordination compounds as efficient DNA-cleaving agents

The DNA-cleavage ability of novel bifunctional heterobimetallic copper-ruthenium complexes is demonstrated by using gel electrophoresis.