DNA-binding and anticancer activity of binuclear gold(I) alkynyl complexes with a phenanthrenyl bridging ligand

3,6-Diethynyl-9,10-diethoxyphenanthrene (4) was synthesized from phenanthrene and employed in the synthesis of the binuclear gold(I) alkynyl complexes (R3P)Au(C≡C-3-[C14H6-9,10-diethoxy]-6-C≡C)Au(PR3) (R = Ph (5a), Cy (5b)). The diyne 4 and complexes 5a and 5b were characterized by NMR spectroscopy, mass spectrometry, and elemental analysis. UV-Vis spectroscopy studies of the metal complexes and precursor diyne show strong π → π* transitions in the near UV region that red shift by ca. 50 nm upon coordination at the gold centers. The emission spectrum of 4 shows an intense fluorescence band centered at 420 nm which red shifts, slightly upon coordination of 4 to gold. Binding studies of 4, 5a, and 5b against calf thymus DNA were carried out, revealing that 4, 5a, and 5b have ≥40% stronger binding affinities than the commonly used intercalating agent ethidium bromide. The molecular docking scores of 4, 5a, and 5b with B-DNA suggest a similar trend in behavior to that observed in the DNA-binding study. Unlike the ligand 4, promising anticancer properties for 5a and 5b were observed against several cell lines; the DNA binding capability of the precursor alkyne was maintained, and its anticancer efficacy enhanced by the gold centers. Such phenanthrenyl complexes could be promising candidates in certain biological applications because the two components (phenanthrenyl bridge and metal centers) can be altered independently to improve the targeting of the complex, as well as the biological and physicochemical properties.This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudi Arabia under grant no. (KEP-44-130-40). The authors, therefore, acknowledge with thanks DSR technical and financial support

DNA-Binding Capabilities and Anticancer Activities of Ruthenium(II) Cymene Complexes with (Poly)cyclic Aromatic Diamine Ligands

Ruthenium(II) arene complexes of the general formula [RuCl(η6-p-cymene)(diamine)]PF6 (diamine = 1,2-diaminobenzene (1), 2,3-diaminonaphthalene (2), 9,10-diaminophenanthrene (3), 2,3-diaminophenazine (4), and 1,2-diaminoanthraquinone (5) were synthesized. Chloro/aqua exchange was evaluated experimentally for complexes 1 and 2. The exchange process was investigated theoretically for all complexes, revealing relatively fast exchange with no significant influence from the polycyclic aromatic diamines. The calf thymus DNA (CT-DNA) binding of the complexes increased dramatically upon extending the aromatic component of the diamines, as evaluated by changes in absorption spectra upon titration with different concentrations of CT-DNA. An intercalation binding mode was established for the complexes using the increase in the relative viscosity of the CT-DNA following addition of complexes 1 and 2. Theoretical studies showed strong preference for replacement of water by guanine for all the complexes, and relatively strong Ru-Nguanine bonds. The plane of the aromatic systems can assume angles that support non-classical interactions with the DNA and covalent binding, leading to higher binding affinities. The ruthenium arenes illustrated in this study have promising anticancer activities, with the half maximal inhibitory concentration (IC50) values comparable to or better than cisplatin against three cell lines.This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudi Arabia under grant no. (KEP-60-130-38)

The potential anticancer activities of platinum(II) complexes with tridentate N'N'N' pincer ligands

519-530Treatment of cis/trans-[PtCl2(N≡CR)2] 1 (R = CH3 (1a), C2H5 (1b), C6H5 (1c), CH2C6H4(p-CH3) (1d)) with 1,3-diiminoisoindoline 2 gives access to the corresponding symmetrical (1,3,5,7,9-pentaazanona-1,3,6,8-tetraenato) platinum(II) complexes [PtCl{NH=C(R)N=C(C6H4)NC=NC(R)=NH}] 3a-d, in good yields (65–77%). The compounds 3a-d have been characterized by IR, 1H, 13C and DEPT-135 NMR spectroscopies, ESI-MS and elemental analyses. GIAO/DFT studies have been performed to confirm the molecular structure of the platinum(II)-pincer 3d by comparing the experimental and theoretical 1H and 13C NMR chemical shifts, and it has shown good correlations between experimental and calculated chemical shifts for proton and carbon with correlation coefficients of 0.9947 and 0.9968, respectively. Molecular electrostatic potential is used to investigate the nucleophilic or electrophilic regions in the molecule 3d. The antimicrobial activities of compounds 3a-d are determined against different bacterial pathogens and yeasts. No toxicity is recorded against Artemia saline as a test organism for 3a-c, while moderate toxicity is found for 3d at 0.62 µM. Comparable antitumor activities are found for 3a-d against human colon HCT116 and human breast (MCF-7) cancer cell lines. The complexes 3a-d have shown good binding affinities to ct-DNA in the range of 6.00´105 to 8.33´105 and the conducted molecular docking studies suggest an intercalation mode of binding with DNA by the isoindole fragment of the ligands. Overall, this class of tridentate ligands have shown good potential in designing platinum(II) complexes with promising biological and anticancer activities. Moreover, the presence of the side chains on the ligands provides great design flexibility by introducing some chemical and/or physical characteristics

The potential anticancer activities of platinum(II) complexes with tridentate N'N'N' pincer ligands

Treatment of cis/trans-[PtCl2(N≡CR)2] 1 (R = CH3 (1a), C2H5 (1b), C6H5 (1c), CH2C6H4(p-CH3) (1d)) with 1,3-diiminoisoindoline 2 gives access to the corresponding symmetrical (1,3,5,7,9-pentaazanona-1,3,6,8-tetraenato) platinum(II) complexes [PtCl{NH=C(R)N=C(C6H4)NC=NC(R)=NH}] 3a-d, in good yields (65–77%). The compounds 3a-d have been characterized by IR, 1H, 13C and DEPT-135 NMR spectroscopies, ESI-MS and elemental analyses. GIAO/DFT studies have been performed to confirm the molecular structure of the platinum(II)-pincer 3d by comparing the experimental and theoretical 1H and 13C NMR chemical shifts, and it has shown good correlations between experimental and calculated chemical shifts for proton and carbon with correlation coefficients of 0.9947 and 0.9968, respectively. Molecular electrostatic potential is used to investigate the nucleophilic or electrophilic regions in the molecule 3d. The antimicrobial activities of compounds 3a-d are determined against different bacterial pathogens and yeasts. No toxicity is recorded against Artemia saline as a test organism for 3a-c, while moderate toxicity is found for 3d at 0.62 µM. Comparable antitumor activities are found for 3a-d against human colon HCT116 and human breast (MCF-7) cancer cell lines. The complexes 3a-d have shown good binding affinities to ct-DNA in the range of 6.00´105 to 8.33´105 and the conducted molecular docking studies suggest an intercalation mode of binding with DNA by the isoindole fragment of the ligands. Overall, this class of tridentate ligands have shown good potential in designing platinum(II) complexes with promising biological and anticancer activities. Moreover, the presence of the side chains on the ligands provides great design flexibility by introducing some chemical and/or physical characteristics

Dna-binding and cytotoxicity of copper(I) complexes containing functionalized dipyridylphenazine ligands

A set of copper(I) coordination compounds with general formula [CuBr(PPh3 )(dppz-R)] (dppz-R = dipyrido[3,2-a:2’,3’-c]phenazine (Cu-1), 11-nitrodipyrido[3,2-a:2’,3’-c]phenazine (Cu-2), 11-cyanodipyrido[3,2-a:2’,3’-c]phenazine (Cu-3), dipyrido[3,2-a:2’,3’-c]phenazine-11-phenone (Cu-4), 11,12-dimethyldipyrido[3,2-a:2’,3’-c]phenazine (Cu-5)) have been prepared and characterized by elemental analysis,1H-NMR and31P-NMR spectroscopies as well as mass spectrometry. The structure of Cu-1 was confirmed by X-ray crystallography. The effect of incorporating different functional groups on the dppz ligand on the binding into CT-DNA was evaluated by absorption spectroscopy, fluorescence quenching of EtBr-DNA adducts, and viscosity measurements. The functional groups affected the binding modes and hence the strength of binding affinities, as suggested by the changes in the relative viscosity. The differences in the quenching constants (Ksv) obtained from the fluorescence quenching assay highlight the importance of the functional groups in altering the binding sites on the DNA. The molecular docking data support the DNA-binding studies, with the sites and mode of interactions against B-DNA changing with the different functional groups. Evaluation of the anticancer activities of the five copper compounds against two different cancer cell lines (M-14 and MCF-7) indicated the importance of the functional groups on the dppz ligand on the anticancer activities. Among the five copper complexes, the cyano-containing complex (Cu-3) has the best anticancer activities.This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudi Arabia under grant no. (KEP-60-130-38)

Toward structure-optical property relationships of ruthenium alkynyl complexes

The aims of this work were to highlight changing trend in the nonlinear optical (NLO) behaviour of ruthenium alkynyl complexes on structure modification. Chapter 1 discusses the theoretical background of NLO properties. This is followed by a brief review on the research that has been conducted in the field of organometallic NLO materials. Chapter 2 is concerned with the synthesis of a series of ruthenium bis-alkynyl complexes varying in ligand composition by chain lengthening and/or changing the arylalkynyl para-substituted functional groups, together with their cyclic voltammetric data and linear optical data. Chapter 3 discusses the strategies for synthesizing wedges with ABC composition and their use in the syntheses of dendrimers with C{u2083}h -symmetry. A series of alkynylruthenium dendrimers with different peripheral groups was made. The electrochemical properties of these dendrimers were assessed, and the linear optical and cubic nonlinear optical properties were studied. Chapter 4 examines the effect of the number of ruthenium centers on dendrimer NLO behaviour. Mono-ruthenium, bi-ruthenium and tri-ruthenium dendrons were synthesized and their linear optical properties studied. Chapter 5 focuses on the electronic communication between ruthenium centers in multi-ruthenium alkynyl complexes. A series of linear and branched ruthenium alkynyl complexes was made. Electrochemical and linear optical properties were examined

PtII versus PdII-assisted [2+3] cycloadditions of nitriles and nitrone. Synthesis of nitrile-derived arylamido platinum(II) and Δ4-1,2,4-oxadiazoline palladium(II) complexes

The reactions of bis(organonitrile) platinum(II) complexes trans-[PtCl2(NCR)2] (R = C6H4(p-HCO), CH2C6H4(p-CH3)) with pyrroline N-oxide −O+NCHCH2CH2CMe2 afford arylamido platinum(II) complexes trans-[PtCl2{(OCR)NCCH2CH2CMe2NH}2] (R = C6H4(p-HCO) (1), CH2C6H4(p-CH3) (2)). The spectral data of 1 and 2 show that the oxadiazoline rings in both cases have opened by a spontaneous NO bond cleavage to form (Z)-p-formyl-N-(5,5-dimethylpyrrolidin-2-ylidene)benzamide or (Z)-N-(5,5-dimethylpyrrolidin-2-ylidene)-2-p-tolylacetamide ligands, respectively, where the N-atoms of the benzamide or acetamide moieties coordinate to platinum(II) metal centre in trans positions. However, the reactions of bis(organonitrile) palladium(II) complexes trans-[PdCl2(NCR)2] with pyrroline N-oxide furnish Δ4-1,2,4-oxadiazoline palladium(II) complexes trans-[PdCl2{NC(R)ONC(H)CH2CH2CMe2}2] (R = C6H4(p-HCO) (3), CH2C6H4(p-CH3) (4)) as the exclusive detected products. Compounds 1–4 have been characterized by IR, 1H, 13C NMR spectroscopy, elemental analyses, ESI+-MS and also, in the case of 1, by single crystal X-ray diffraction analysis.peerReviewe

Evaluation of the Anticancer and DNA-Binding Characteristics of Dichloro(diimine)zinc(II) Complexes

Several metal diimine complexes have been reported to possess anticancer properties. To evaluate the anticancer properties of tetrahedral zinc(II) diimine complexes, six complexes were synthesized with the general formula M(N^N)Cl2 {where M = Zn, Pt and N^N = 2,2’-biquinoline (1), 2,2’-dipyridylketone (2) and 4-((pyridine-2-ylmethylene)amino)phenol (3)}. In general, the intrinsic DNA-binding constants for the different compounds exhibited values within close proximity; the changes in the viscosity of the CT-DNA upon binding to the compounds suggest intercalation-binding mode. Molecular docking study predicted that complexes containing the highly planar ligand 2,2’-biquinoline are capable to establish π–π interactions with nucleobases of the DNA; the other four complexes engaged in donor–acceptor interactions with DNA nucleobases. The six complexes and two reference drugs (cisplatin and sunitinib) were tested against two cancer cell lines (COLO 205 and RCC-PR) and one normal cell line (LLC-MK2), highlighting the better performance of the zinc(II) complexes compared to their platinum(II) analogues. Moreover, zinc(II) complexes have higher selectivity index values than the reference drugs, with promising anticancer properties