Selective Metal-Ligand Bond-Breaking Driven by Weak Intermolecular Interactions: From Metamagnetic Mn(III)-Monomer to Hexacyanoferrate(II)-Bridged Metamagnetic Mn2Fe Trimer.

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 example where metal-ligand bonds dissociate in an irreversible way, helped by a large number of weak intermolecular interactions that surpass the energy of the metal-ligand bond. Thus, we describe the design and synthesis of trinuclear Mn2Fe complex {[Mn(L)(H2O)]2Fe(CN)6},2- starting from a mononuclear Mn(III)-Schiff base complex: [Mn(L)(H2O)Cl] (1) and [Fe(CN)6]4- anions. This reaction implies the dissociation of Mn(III)-Cl coordination bonds and the formation of Mn(III)-NC bonds with the help of several intermolecular interactions. Here, we present the synthesis, crystal structure, and magnetic characterization of the monomeric Mn(III) complex [Mn(L)(H2O)Cl] (1) and of compound (H3O)[Mn(L)(H2O)2]{[Mn(L)(H2O)]2Fe(CN)6}·4H2O (2) (H2L = 2,2'-((1E,1'E)-(ethane-1,2-diylbis(azaneylylidene))bis(methaneylylidene))bis(4-methoxyphenol)). Complex 1 is a monomer where the Schiff base ligand (L) is coordinated to the four equatorial positions of the Mn(III) center with a H2O molecule and a Cl- ion at the axial sites and the monomeric units are assembled by π-π and hydrogen-bonding interactions to build supramolecular dimers. The combination of [Fe(CN)6]4- with complex 1 leads to the formation of linear Mn-NC-Fe-CN-Mn trimers where two trans cyano groups of the [Fe(CN)6]4- anion replace the labile chloride from the coordination sphere of two [Mn(L)(H2O)Cl] complexes, giving rise to the linear anionic {[Mn(L)(H2O)]2Fe(CN)6}2- trimer. This Mn2Fe trimer crystallizes with an oxonium cation and a mononuclear [Mn(L)(H2O)2]+ cation, closely related to the precursor neutral complex [Mn(L)(H2O)Cl]. In compound 2, the Mn2Fe trimers are assembled by several hydrogen-bonding and π-π interactions to frame an extended structure similar to that of complex 1. Density functional theoretical (DFT) calculations at the PBE1PBE-D3/def2-TZVP level show that the bond dissociation energy (-29.3 kcal/mol) for the Mn(III)-Cl bond is smaller than the summation of all the weak intermolecular interactions (-30.1 kcal/mol). Variable-temperature magnetic studies imply the existence of weak intermolecular antiferromagnetic couplings in both compounds, which can be can cancelled with a critical field of ca. 2.0 and 2.5 T at 2 K for compounds 1 and 2, respectively. The magnetic properties of compound 1 have been fit with a simple S = 2 monomer with g = 1.959, a weak zero-field splitting (|D| = 1.23 cm-1), and a very weak intermolecular interaction (zJ = -0.03 cm-1). For compound 2, we have used a model with an S = 2 monomer with ZFS plus an S = 2 antiferromagnetically coupled dimer with g = 2.009, |D| = 1.21 cm-1, and J = -0.42 cm-1. The metamagnetic behavior of both compounds is attributed to the weak intermolecular π-π and hydrogen-bonding interactions.

A ZnII complex of ornidazole with decreased nitro radical anions that is still highly active on Entamoeba histolytica.

A monomeric complex of ZnII with ornidazole [Zn(Onz)2Cl2] decreases formation of the nitro-radical anion (R-NO2˙-), and this is realized by recording it in an enzyme assay using xanthine oxidase, which is a model nitro-reductase. Although the formation of R-NO2˙- is essential for drug action, as it is also associated with neurotoxic side effects, it is imperative to control its generation in order to avoid excess presence. With a decrease in R-NO2˙-, while the neurotoxic side effects should decrease, it can be expected that a compromise with regard to therapeutic efficacy will be seen since the complex will be less active in the free radical pathway. Since R-NO2˙- is crucial for the functioning of 5-nitroimidazoles, we attempted to find out if its biological activity is affected in any way in our effort to control its formation. For this purpose, Entamoeba histolytica (HM1:IMS Strain) was chosen as a biological target to realize the performance of the complex with respect to ornidazole (R-NO2). The experiments revealed that the complex not only compares well with ornidazole, but in fact, under longer exposure times, it also performs better than it. This efficacy of the complex was seen despite a decrease in R-NO2˙-, as identified by an enzyme assay, and this was probably due to certain attributes of the complex formation that are not known for ornidazole. These attributes outweigh any loss in efficacy in the free radical pathway following complex formation. This is certainly an advantage of complex formation and helps to improve the therapeutic index. This study has attempted to look at some of the possible reasons why the complex performs better than ornidazole. One reason is its ability to bind to DNA better than ornidazole does, and this can be understood by following the interaction of ornidazole and its Zn(ii) complex with calf-thymus DNA using cyclic voltammetry. Therefore, this study showed that despite a decrease in R-NO2˙-, the complex does not compromise its efficacy, and this was examined using a biological target. In addition, the complex is likely to have less toxic side effects on the host of the disease-causing microbes.

Activity of CoII-Quinalizarin: A Novel Analogue of Anthracycline-Based Anticancer Agents Targets Human DNA Topoisomerase, Whereas Quinalizarin Itself Acts via Formation of Semiquinone on Acute Lymphoblastic Leukemia MOLT-4 and HCT 116 Cells.

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.

A new multicomponent salt of imidazole and tetrabromoterepthalic acid: structural, optical, thermal, electrical transport properties and antibacterial activity along with Hirshfeld surface analysis.

Herein, we report the structural, optical, thermal and electrical transport properties of a new multicomponent salt (TBTA(2-))·2(IM(+))·(water) [TBTA-IM] of tetrabromoterepthalic acid (TBTA) with imidazole (IM). The crystal structure of TBTA-IM is determined by both the single crystal and powder X-ray diffraction techniques. The structural analysis has revealed that the supramolecular charge assisted O(-)⋯HN(+) hydrogen bonding and Br⋯π interactions play the most vital role in formation of this multicomponent supramolecular assembly. The Hirshfeld surface analysis has been carried out to investigate supramolecular interactions and associated 2D fingerprint plots reveal the relative contribution of these interactions in the crystal structure quantitatively. According to theoretical analysis the HOMO-LUMO energy gap of the salt is 2.92 eV. The salt has been characterized by IR, UV-vis and photoluminescence spectroscopic studies. It shows direct optical transition with band gaps of 4.1 eV, which indicates that the salt is insulating in nature. The photoluminescence spectrum of the salt is significantly different from that of TBTA. Further, a comparative study on the antibacterial activity of the salt with respect to imidazole, Gatifloxacin and Ciprofloxacin has been performed. Moreover, the current-voltage (I-V) characteristic of ITO/TBTA-IM/Al sandwich structure exhibits good rectifying property and the electron tunneling process governs the electrical transport mechanism of the device.