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Metal–ligand coordination interactions are usually much stronger than weak intermolecular interactions. Nevertheless, here, we show experimental evidence and theoretical confirmation of a very rare...

Herein, we report the molecular and supramolecular structure, photoluminescence, redox behavior and product selective catalytic activity of [Cu2(oxalate)(1,10-phen)2Cl2] (where 1,10-phen = 1,10-phenanthroline) synthesized by using hydrophilic oxalate as bridging ligand and the hydrophobic 1,10-phen as the blocker ligand. Structural analysis reveals that this binuclear Cu(II)-complex crystallizes in achiral monoclinic P21/n space group and it has a 3D supramolecular structure. Each Cu-center displays five coordinated distorted square pyramidal geometry. Two such Cu centers are connected by oxalato-bridge to form the bi-nuclear-metal core and two 1,10-phen molecules block the outer periphery of the core and restrains further polymerization. These binuclear metallic units are connected by supramolecular hydrogen bonding and π⋯π interactions to form a 3D supramolecular architecture. The complex is stable up to 230 °C. A reversible redox couple centered at (E1/2) ∼ −27 mV with ΔEp ∼ 206 mV corresponding to the CuII/I couple was detected in the cyclic voltammogram of the complex in acetonitrile. The complex shows emission maxima at 451 and 480 nm upon excitation at 340 nm due to π-π* transition in the aromatic π-rings of 1,10-phenanthroline. Density functional analysis has been performed to explore the molecular structure and character of the orbitals within the complex. Due to the presence of five coordinated Cu-centers, the lewis acidic catalytic activity of the complex has been studied. It exhibits selective oxidation behavior for alkenes in presence of several oxidants. It shows 100% selectivity with 70% conversion for the oxidation of cis-cyclooctene to corresponding epoxide at 50 °C in presence of H2O2 as oxidant in acetonitrile.

Quinalizarin (THAQ), a hydroxy-9,10-anthraquinone analogue of the family of anthracycline anticancer drugs and an inhibitor of protein kinase, was observed for its anticancer activity. Because apart from showing anticancer activity, anthracyclines and their analogues also show cardiotoxic side effects, believed to be addressed through metal complex formation; an effort was made to realize this by preparing a CoII complex of THAQ. The aim of this study was to find out if complex formation leads to a decrease in the generation of intermediates that are responsible for toxic side effects. However, because this also meant that efficacy on cancer cells would be compromised, studies were undertaken on two cancer cell lines, namely, acute lymphoblastic leukemia (ALL) MOLT-4 and HCT116 cells. The complex decreases the flow of electrons from NADH to molecular oxygen (O2) in the presence of NADH dehydrogenase forming less semiquinone than THAQ. It showed increased affinity toward DNA with binding constant values remaining constant over the physiological pH range unlike THAQ (for which decrease in binding constant values with increase in pH was observed). The complex is probably a human DNA topoisomerase I and human DNA topoisomerase II poison acting by stabilizing the covalent topoisomerase-cleaved DNA adduct, a phenomenon not observed for THAQ. Activity of the compounds on cancer cells suggests that THAQ was more effective on ALL MOLT-4 cells, whereas the complex performed better on HCT116 cells. Results suggest that the formation of semiquinone probably dominates the action because of THAQ, whereas the performance of the complex is attributed to increased DNA binding, inhibition of topoisomerase, and so forth. Inspite of a decrease in the generation of superoxide by the complex, it did not hamper efficacy on either cell line, probably compensated by improved DNA binding and inhibition of topoisomerase enzymes which are positive attributes of complex formation. A decrease in superoxide formation suggests that the complex could be less cardiotoxic, thus increasing its therapeutic index.

Herein, we have reported the synthesis, crystal structure, thermogravimetric property, and photoluminescence activity of a new Cu-based metal organic framework (MOF): {[Cu2(2,5-pdc)2(ald-4)(H2O)2]·3H2O,MeOH}n (where 2,5-pdc = 2,5-pyridine-dicarboxylate, ald-4 = aldrithiol-4) along with catalytic activity of CuO nanoparticles (Cu-NPs) derived from the MOF for green synthesis of organic molecules having biological relevance. The regular arrangement of metal centers and the presence of oxygen and carbon in metal–organic frameworks (MOFs) enable us to utilize them as template/precursor for the synthesis of monodispersed metal-oxide and metal-carbide nanoparticles having a high surface area with well-defined and uniform morphology. The MOF derived oxide nanoparticles generally exhibit improved catalytic activities and product selectivity and significantly reduce the chemical waste production. The structural analysis has revealed that in the complex under investigation the 2,5-pdc bridges the Cu(II) centers to ...

Emodin, a hydroxy-9,10-anthraquinone, resembles anthracycline anticancer drugs at the core and possesses anticancer activities. A CuII complex of emodin [CuII(emod)2]2− was synthesized and its crystal structure was determined by Rietveld refinement of the PXRD data by using an appropriate structural model based on spectroscopy. This is the third report on the crystal structure of a hydroxy-9,10-anthraquinone with a 3d-transition metal ion. Since the formation of reactive oxygen species (ROS) by anthracycline-based anticancer drugs is important for antitumor activity and given the fact that the generation of ROS is responsible for cardiotoxic side effects, it is essential to be able to control their formation. Complex formation decreases ROS generation and could thereby lead to a decrease in cardiotoxic side effects. However, in an attempt to decrease complications, there is also the possibility of compromising the therapeutic efficacy. For this reason, the activities of emodin and its modified form [Cu(II) complex] were studied on the carcinoma cell lines HeLa and Hep G2 to see how they compared with each other in terms of performance. Studies were also performed on WI 38 lung fibroblast normal cells. The studies revealed that, in spite of the decreased ROS formation, followed by the DCFDA assay, the Cu(II) complex showed better activity on carcinoma cell lines. This suggests that the complex has other attributes that enable it to perform better than emodin. Consequently, one such attribute, namely DNA binding, was thoroughly investigated by varying the ionic strength and the temperature of the medium. It was found that the complex was able to bind DNA better than emodin, and, more importantly, since both generate a good amount of anionic species in solution under increased ionic strength of the medium, both bind DNA better; the increase in binding with increase in ionic strength being higher for the complex. The study suggests that with a substantial decrease in ROS generation by the complex, there are likely to be less toxic side effects, which is a key advantage of the complex, leading to an improvement in the therapeutic index. The complex showed almost no activity on WI 38 normal cells.

In an attempt to overcome limitations of Curcumin from being an important molecule in biology and medicine, a monomeric complex of CuII [Cu(Cur)(OCOCH3)(H2O)] was prepared. Physico-chemical studies in solution using copper acetate and Curcumin indicate formation of a 1:2 CuII:Curcumin species. However, attempts to prepare it always led to the formation of a 1:1 CuII:Curcumin species, if CuII-acetate was used as the starting material. In the absence of a single crystal or an appropriate powder X ray diffraction data that would allow solving of the structure, it was arrived at by spectroscopy guided DFT calculations. Unlike Curcumin, the prepared complex was stable under physiological conditions, an advance achieved through complex formation. Effective binding of the complex to DNA with an ability to enhance cellular uptake owing to the presence of CuII are other benefits of complex formation that might increase its cytotoxic potential. The complex has a reasonably strong affinity for DNA realized from binding constant values obtained with calf thymus DNA at different temperatures in the range 25 °C–35 °C. This enabled an evaluation of thermodynamic parameters (ΔH, ΔS and ΔG), that helped in determining the mode of binding between the complex and DNA as realized from a correlation of thermodynamic signatures to binding types. The study may be considered a case of pseudo-binding of Curcumin to DNA since the complex containing a Curcumin bound the metal ion does not dissociate in solution under physiological conditions, i.e. remains as one unit. Hence binding of the complex to DNA is also the binding of Curcumin to it present as one “single unit”, a major advancement based on a biophysical approach. Besides, aspects like stability of the complex in solution, prevention of degradation of Curcumin in aqueous buffer or biological milieu, binding with mammalian DNA are other aspects that are significant for use of the complex on biological targets.

The formation of reactive oxygen species (ROS) by anthracycline anticancer drugs is essential for their antitumor activity but they also make these drugs cardiotoxic. When complexed with metal ions there is a decrease in ROS formation and therefore in cardiotoxicity. Interestingly, in spite of producing fewer ROS, some of the complexes are effective antitumor agents, often better than the parent anthracycline. Purpurin (LH3), a hydroxy-9,10-anthraquinone, resembles doxorubicin at the core. An MnII complex of LH3 [MnII(LH2)2] was synthesized to see the extent to which the complex resembles metal–anthracyclines with regard to structure and function. The crystal structure was determined by Rietveld refinement of PXRD data using an appropriate structural model developed on the basis of spectroscopic information. This is only the second report on the crystal structure of a hydroxy-9,10-anthraquinone with a 3d-transition metal ion. Bond lengths and bond angles were obtained by structural refinement. The structure is supported by DFT calculations. DNA binding of the complex is slightly better than for purpurin but more importantly unlike purpurin, the binding constant values remained constant even with an increase in the pH of the medium. The NADH dehydrogenase assay and the DCFDA-ROS generation assay showed that generation of superoxide in the former and ROS in general in the latter were significantly less for the complex than for purpurin. Even with decreased ROS formation, the complex is able to maintain the biological activity of purpurin.

Alizarin (DHA), a simple analogue of the anthracycline core was used to form a complex with MnII to see if the complex matches the efficacy of anthracyclines. It was characterized by spectroscopic techniques, mass spectrometry and TGA. In the absence of a single crystal, the structure was obtained by computational techniques. Interaction of the complex with DNA at different ionic strength and pH was compared with anthracyclines to see if it addresses some of the shortcomings of hydroxy-9,10-anthraqunones in general and DHA in particular when compared to anthracyclines. Increased affinity of the complex towards DNA and that its binding constant values do not decrease with increase in pH or decrease in ionic strength of the medium are positive attributes of complex formation. This is significant since cancer patients often experience fluctuation of pH and ionic strength in body fluids during treatment that affect efficacy of drugs. The complex decreases the flow of electrons from NADH to molecular oxygen owing to decreased semiquinone formation; a fact important for controlling cardiotoxicity. Experiments on ROS depletion in HeLa, Hep G2 and WI 38 lung fibroblast cells by the H2DCFDA assay suggests a shift in mechanism for the complex from that of DHA. Loss in efficacy due to decrease in semiquinone formation by the complex is made up by other attributes of complex formation that eventually promote cytotoxicity. Compounds were tried on HeLa, Hep G2 and WI 38 lung fibroblast cells. An effort was made to correlate aspects of semiquinone formation, ROS generation and interaction with DNA with results obtained on two cancer cell lines and a normal cell line.