Non-leaving Ligands Research Articles

Slowing the reactivity of dicyclometalated Pd(II) complexes through the 2,6-bis(N-heterocyclic carbene)pyridine (C^N^C) non-leaving ligands: kinetic and computational study

Slowing the reactivity of dicyclometalated Pd(II) complexes through the 2,6-bis(N-heterocyclic carbene)pyridine (C^N^C) non-leaving ligands: kinetic and computational study

The effect of the chelate ligand on the rate of chloride substitution from Pt(II) complexes with picolyl and isoquinolinylcarboxamide moieties on the non-leaving ligand

Substitution reactions of four Pt(II) complexes, namely; N-(2-picolyl)picolinamide-platinum(II) chloride (Pt3), N-(8-quinolyl)pyridine-2-carboxamide platinum(II) chloride (Pt4), N-(8-quinolyl)-3-isoquinolinecarboxamide platinum(II) chloride (Pt5) and N-(8-quinolinyl)-1-isoquinolinecarboxamide platinum(II) chloride (Pt6), were studied with biorelevant nucleophiles, viz. thiourea (TU), N,N′-dimethylthiourea (DMTU) and N,N,N′,N′-tetramethylthiourea (TMTU) under pseudo first order conditions as a function of concentration and temperature using the stopped flow spectrophotometer. The observed pseudo first order rate constants for the substitution reactions obey the rate law kobs = k2[Nu]. The reactivity of the studied complexes depends on strength of π-backbonding of the attached ligands, which is enhanced by the strong electron withdrawing nature of the carboxamide group on the non-leaving ligands of Pt(II) complexes. Quinoline moieties of Pt5 and Pt6 lie out-of-the square plane, resulting in enhanced reactivity due to the aided entrapment of the nucleophile by the non-planar groups of the ligand. Negative activation entropies and positive enthalpies of activation support an associative mode of activation.

Tandem mass spectrometry characterization of a conjugate between oleuropein and hydrated cis‐diammineplatinum(II)

Oleuropein (Ole) has been claimed to mitigate cisplatin (CP)-induced acute injury in kidney and liver of mice. In vitro reactivity of hydrated CP species with Ole, and an Ole metabolite, hydroxytyrosol (HT), is of great interest as the preliminary step for gathering in vivo information on the possible physiological role of the Ole/HT-cis-diammineplatinum(II) (Ole/HT-cis-DAP) conjugate. Reversed-phase liquid chromatography coupled to electrospray ionization mass spectrometry using a linear ion trap instrument (RPLC/ESI-MS) and tandem mass (MS/MS) measurements, both in positive and negative ion mode, revealed the molecular identity of platinum-based conjugates. The Ole-cis-DAP conjugate (i.e., C25 H36 N2 O13 PtII ) features two cis-ammine non-leaving ligands and a bidentate catechol ligand moiety belonging to Ole; the coordination of the central Pt(II) is square-planar with non-equivalent bond angles compared with the ideal arrangement of 90°. HT, the free Ole metabolite excreted in human urine, acts as bidentate O,O-donor ligand of cis-DAP as well. The first evidence, together with structural information, is provided about the in vitro formation of a conjugate between cis-DAP and Ole or its urinary metabolite HT. Presuming that such conjugates are also generated in vivo, the mechanisms by which they might contribute to reduce CP toxicity remain to be elucidated.

A novel Trans-Pt(II) complex bearing 2-acetoxymethylbenzimidazole as a non-leaving ligand (trans-[Pt(AMBi)2Cl2]): Synthesis, antiproliferative activity, DNA interaction and molecular docking studies compared with its cis isomer (cis-[Pt(AMBi)2Cl2

Trans-[Pt(AMBi)2Cl2 (1) in which AMBi is 2-acetoxymethylbenzimidazole, was synthesized and characterized by spectroscopic methods. Novel complex 1 was evaluated for its potential antiproliferative effect against three human cancer cell lines, including HeLa (human cervix cancer), MCF-7 (human breast cancer) and A549 (human non-small-cell lung cancer) in comparison with those of cis-[Pt(AMBi)2Cl2 (2) and cisplatin by means of the MTT assay. Interaction of complexes 1, 2 and cisplatin with pBR322 plasmid DNA and their restriction endonuclease reactions by BamHI and HindIII enzymes were studied by agarose gel electrophoresis. Cytotoxicity tests showed that complex 1 exhibited similar in vitro cytotoxicity profile as compared with cisplatin whereas better than corresponding cis isomer against MCF-7 and A549 human cancer cell lines. The electrophoretic mobility shift assay showed that although no comigration of the Form I and II bands of plasmid DNA was observed for complex 1 at the concentrations tested, the binding of complex 1 was able to prevent partially BamHI digestion for concentrations ranging from 40 to 160 μM while having no inhibitory effect on HindIII activity in the digestion studies with restriction enzymes. Molecular docking studies on DNA were carried out to explore the binding mode and the best orientation of the complexes 1 and 2 to DNA.

The influence of the nonleaving group on the anticancer activity of tetrachlorido platinum(IV) complexes with pyridine/bipyridine derivatives

Due to their inertness, platinum(IV) complexes are well known potential candidates to improve the pharmacological properties and selective cellular uptake of commonly used platinum(II) anticancer agents. In these 6-coordinate prodrugs, the equatorial nonleaving groups are the only ligands which remain in the final Pt-DNA adducts and directly affect the DNA binding property. In an effort to discover the structure–activity relationship; in this report, two novel platinum(IV) complexes, trans-[Pt(3phpy)2Cl4] (1) and [Pt(4dtb-bpy)Cl4].DMSO (2) (3phpy = 3-phenylpyridine and 4dtb-bpy = 4,4′-di-tert-butyl-2,2′-bipyridine) were prepared and fully characterized. Their in vitro activity was evaluated and compared with those of similar platinum(IV) complexes, containing unbranched ligands, trans-[Pt(py)2Cl4] and [Pt(bpy)Cl4]. Interestingly, complex 1, with phenylpyridine nonleaving ligands, demonstrated further antiproliferative properties among the studied platinum(IV) prodrugs. Moreover, the apoptosis rate in cell lines was also determined using flow cytometry. Furthermore, the resistance factor of complexes 1 and 2 were 1.1 and 1.3, respectively, using wild-type and cisplatin-resistant A2780 cell lines.

Reactivity of cis‐platinum(II) complexes with 2‐(4‐substituted)phenylthiomethyl)quinoline nonleaving ligands toward thiourea nucleophiles

AbstractThe sequential substitution of aqua ligands from [Pt{2‐(phenylthiomethyl)quinoline}(H2O)2]CF3SO3, Pt(L1), [Pt{2‐(4‐tert‐butylphenylthiomethyl)quinoline}(H2O)2]CF3SO3 Pt(L2), and [Pt{2‐(4‐fluorophenylthiomethyl) quinoline}(H2O)2]CF3SO3 Pt(L3) by thiourea nucleophiles (Nu) was studied under pseudo–first‐order conditions as a function of concentration and temperature using stopped‐flow and UV‐visible spectrophotometric techniques. The observed pseudo–first‐order rate constants for the substitutions can be described by the rate law: kobs(1/2) = k2(1/2)[Nu], where the subscript denotes the consecutive substitution steps. The first aqua ligand was substituted opposite to the strong σ‐trans‐directing thioether followed by the aqua ligand opposite to the quinoline or pyridine moieties. Second‐order rate constants, k2(1st), for the substitution of the first aqua ligand by thiourea nucleophiles ranged between 9 and 22 M−1 s−1 for Pt(L1), 86 and 326 M−1 s−1 for Pt(L2), and 58 –287 M−1 s−1 for Pt(L3). The ranges of the second‐order rate constant, k2(2nd), were always lower than the k2(1st)’s and are 0.3‐9 M−1 s‐1 for Pt(L1), 2‐20 M−1 s−1 for Pt(L2), and 0.3‐5 M−1 s−1 for Pt(L3). Aqua substitution from Pt(L2) is slower for both steps than from Pt4, its pyridyl derivative from our previous study. A Job's method of continuous variation plot suggests a species with a metal‐to‐nucleophile ratio of 1:3 as the ultimate product of the chloride substitution from the Pt(II) complexes by the incoming thiourea nucleophiles. The high and negative activation entropy and low and positive activation enthalpy values support an associative mechanism of activation, characteristic of substitution reactions occurring in square‐planar complexes.

Aqua substitution from mononuclear Pt(II) complexes with 2-(pyrazol-1-ylmethyl)quinoline non-leaving ligands

The rates of aqua substitution from [Pt{2-(pyrazol-1-ylmethyl)quinoline}(H2O)2](ClO4)2, [Pt(H2Qn)], [Pt{2-(3,5-dimethylpyrazol-1-ylmethyl)quinoline}(H2O)2](ClO4)2, [Pt(dCH3Qn)], [Pt{2-[(3,5-bis(trifluoromethyl)pyrazol-1-ylmethyl]quinoline}(H2O)2](ClO4)2, [Pt(dCF3Qn)], and [Pt{2-[(3,5-bis(trifluoromethyl)pyrazol-1-ylmethyl]pyridine}(H2O)2](ClO4)2, [Pt(dCF3Py)], with three sulfur donor nucleophiles were studied. The reactions were followed under pseudo-first-order conditions as a function of nucleophile concentration and temperature using a stopped-flow analyzer and UV/visible spectrophotometry. The substitution reactions proceeded sequentially. The second-order rate constants for substituting the aqua ligands in the first substitution step increased in the order Pt(dCH3Qn) < Pt(dCF3Qn) < Pt(H2Qn) < Pt(dCF3Py), while that of the second substitution step was Pt(dCH3Qn) < Pt(dCF3Qn) < Pt(dCF3Py) < Pt(H2Qn). The reactivity trends confirm that the quinoline substructure in the (pyrazolylmethyl)quinoline ligands acts as an apparent donor of electron density toward the metal center rather than being a π-acceptor. Measured pKa values from spectrophotometric acid–base titrations were Pt(H2Qn) (pKa1 = 4.56; pKa2 = 6.32), Pt(dCH3Qn) (pKa1 = 4.88; pKa2 = 6.31), Pt(dCF3Qn) (pKa1 = 4.07; pKa2 = 6.35), and Pt(dCF3Py) (pKa1 = 4.76; pKa2 = 6.27). The activation parameters from the temperature dependence of the second-order rate constants support an associative mechanism of substitution.

Structure-activity relationship and apoptosis induction in A549 cells by the potential anticancer compound cis-bis(3-aminoflavone)dichloroplatinum(II)

cis-DDP (cis-diamminedichloroplatinum(II), CAS 15663-27-1) is widely used in chemotherapy of many types of cancer. However, besides effectiveness, it gives many side effects which limit its clinical application. Therefore, nowadays studies are focused on searching for novel analogs of cis-DDP, at least equally effective in chemotherapy but less toxic. One of them might be cis-BAFDP (cis-bis(3-aminoflavone)dichloroplatinum(II)) with one of the hydrogen atoms of the amino group of cis-DDP replaced by a flavone ring. 3-Aminoflavone (AF) which posseses the desired NH2 group has been used as non-leaving ligand. The complex has been obtained in the reaction of AF and K2PtCl4. There are no data concerning evaluation of structural studies of cis-BAFDP, the beneficial anticancer properties of which were proved in vitro and in vivo. Therefore it was worthwhile to undertake a confirmation of the chemical structure of this compound by applying various spectroscopic techniques especially because of its potential pharmacological application. With this aim in mind this compound was characterized by: IR, 1H NMR, 195Pt NMR, UV absorption and fluorescence spectroscopy. Moreover, stronger apoptosis induction by cis-BAFDP than cis-DDP in the human nonsmall cancer cell line A549 was observed using Hoechst 33258/propidium iodide double staining.

Platinum(IV) coordination compounds containing 5-methyl-1,2,4-triazolo[1,5- a]pyrimidin-7(4 H)-one as nonleaving ligand. Molecular and cytotoxicity in vitro characterization

Novel platinum(IV) coordination compounds with 5-methyl-1,2,4-triazolo[1,5- a]pyrimidin-7(4 H)-one (HmtpO): cis– trans-[PtCl 2(OH) 2(NH 3)(HmtpO)] ( 1), cis– trans-[PtCl 5(HmtpO)][(CH 3) 2NH 2] ( 2) have been prepared and structurally characterized by spectroscopic methods ( 1H, IR and X-ray crystallography ( 2)). The X-ray results indicate that the local geometry around the platinum(IV) centre approximates a typical octahedral arrangement with nitrogen atom N3 of the HmtpO and three chloride atoms in equatorial positions. The remaining two axial positions are occupied by two chlorides. The preliminary assessment of antitumor properties of ( 1) was performed as an in vitro antiproliferative activity against HL-60 human acute promyelocytic leukemia and HCV29T bladder cancer. The cis– trans-[PtCl 2(OH) 2(NH 3)(HmtpO)] ( 1) exhibits higher cytotoxic activity against HL-60 (IC 50 = 6.4 μM) than cisplatin.

Genotoxic effects of irinotecan combined with the novel platinum(II) complexes in human cancer cells

Combination chemotherapy has become increasingly important as synergistic drugs enable to achieve therapeutic effects at substantially lower doses and limited spectrum of side effects. Irinotecan as a one of the camptothecin analogues has shown a broad spectrum of antitumor activity against various malignancies. It is commonly used in treatment of gastrointestinal and pulmonary cancer. In this study were measured the effect of the novel platinum(II) complexes: cis-[PtCl 2(4-pmOpe) 2] and trans-[PtCl 2(4-pmOpe) 2], with diethyl (pyridine-4-ylmethyl)phosphates (4-pmOpe) as non-leaving ligands, on genotoxicity of irinotecan in human cancer cells. Irinotecan showed genotoxic activity in combination with the new platinum(II) derivatives in cancer cells. Combination of irinotecan with cis-[PtCl 2(4-pmOpe) 2] or trans-[PtCl 2(4-pmOpe) 2] resulted in significant increase in DNA damage in A549 and HT29 cells when compared to effects of irinotecan or platinum(II) complexes used separately. The highest degree of DNA migration in the comet tails was found after the cancer cells were treated with irinotecan and trans-[PtCl 2(4-pmOpe) 2]. In addition, the analysis of DNA repair revealed that irinotecan in combination with trans-[PtCl 2(4-pmOpe) 2] induced unrepairable DNA damage suggesting the poor recognition of the damage by HMG proteins and other repair mechanisms. Thus, genotoxicity of irinotecan was modulated by the structurally different DNA–platinum adducts formed by novel platinum(II) complexes. These data suggest that the use of irinotecan with novel platinum(II) complexes may represent a new strategy for pharmacotherapy in cancer.

Energetics, Conformation, and Recognition of DNA Duplexes Modified by Methylated Analogues of [PtCl(dien)]+

In early studies of empirical structure-activity relationships, monodentate Pt(II) complexes were considered to be biologically inactive. Examples of such inactive monodentate Pt(II) compounds are [PtCl(dien)]+ (dien=diethylenetriamine) and [PtCl(NH3)3]+. DNA is considered the major biological target of platinum compounds. Thus, monodentate DNA binding of Pt(II) compounds was previously expected to display insignificant biological effects because it was assumed to affect DNA conformation and downstream cellular processes markedly less than the cross-links of bifunctional Pt(II) complexes. More recently it was shown that some monodentate Pt(II) complexes do exhibit biological effects; the active monodentate Pt(II) complexes commonly feature bulkier amine ligands than the hitherto used dien or NH(3) groups. We were therefore interested in determining whether a simple but marked enhancement of the bulkiness of the dien ligand in monodentate [Pt(NO3)(dien)]+ by multiple methylation of this ligand affects the early phases in which platinum compounds exert their biological activity. More specifically, the goals of this study, performed in cell-free media, were to determine how the modification of DNA duplexes by methylated analogues of [Pt(NO3)(dien)]+ affects their energetics and how the alterations of this biophysical parameter are reflected by the recognition of these duplexes by DNA polymerases and the DNA repair system. We have found that the impact of the methylation of [Pt(NO3)(dien)]+ on the biophysical properties of DNA (thermodynamic, thermal, and conformational properties) and its biochemical processes (DNA polymerization and the repair of DNA adducts) is remarkable. Hence, we conclude that monodentate DNA binding of Pt(II) compounds may considerably affect the biophysical properties of DNA and consequently downstream cellular processes as a result of a large increase in the bulkiness of the nonleaving ligands in this class of metal complex.

Genotoxicity of novel trans-platinum(II) complex with diethyl (pyridin-4-ylmethyl)phosphate in human non-small cell lung cancer cells A549

The dynamic development of metal-containing anticancer drugs has started since the discovery of cis-diamminedichloroplatinum(II). For many years it was believed that trans platinum(II) compounds were non-active as antitumour agents because trans-diamminedichloroplatinum is biologically inactive although it binds to DNA and also forms monoadducts and cross-links. In the present work the ability of a novel platinum(II) compound trans-[PtCl 2(4-pmOpe) 2] to induce DNA damage in human non-small cell lung cancer cells A549 was examined using the alkaline comet assay. The obtained results revealed that the novel trans platinum(II) complex induced DNA strand breaks, which were effectively repaired during 2 h of post-incubation, and cross-links which remained unrepaired under these test conditions. Apart from that, the modified comet assay with incubation with proteinase K was used to verify the ability of trans-[PtCl 2(4-pmOpe) 2] and cis-DDP to form DNA–protein cross-links. It has been proved that only trans-[PtCl 2(4-pmOpe) 2] complex exhibits the ability to induce DNA–protein cross-links. The results suggest a different mechanism of action of this compound in comparison to cis-DDP. It seems that trans geometry and the presence of two diethyl (pyridin-4-ylmethyl)phosphates as non-leaving ligands can determine dissimilar properties of the adducts formed on DNA and the different mechanism of action of trans-[PtCl 2(4-pmOpe) 2] and in consequence the efficacy in killing cancer cells.

Comparative studies on the mechanism of cytotoxic action of novel platinum II complexes with pyrazole ligands

In search for new platinum-based anticancer drugs, four cisplatin analogues, which contain pyrazole rings as non-leaving ligands, have been synthesized: cis-PtCl 2(3,5-DM HMPz) 2, cis-PtCl 2(Pz) 2, cis-PtCl 2(ClMPz) 2, and cis-PtCl 2(HMPz) 2, where Pz = pyrazole, H = hydroxyl, M = methyl. We tested their cytotoxicity, apoptosis induction ability, DNA damaging and modification properties comparing them in respect to the parent compound. The cytotoxic activity of these platinum pyrazole complexes toward the murine leukemia cell line was 2.9–3.8 times lower than actvity of cisplatin. The tested compounds varied in their mechanism of action by producing different DNA lesions. The most interesting compound seems to be the complex with chloromethyl groups at N1 of pyrazole rings, which exhibited the highest ability to form bifunctional adducts with DNA in vitro.

Trans-Platinum Complexes with Promising Antitumor Properties

Wide range of dose-limiting toxicities and tumor resistance to drug are significant limitations of the successful use of cis-diamminedichloroplatinum (cisplatin). For a long time it was believed that generally trans-isomers of platinum containing complexes are devoid of biological activity. Data accumulated by the structure-activity relationship studies up to date, confirm that trans-platinum(II) and trans-platinum(IV) complexes often exhibit enhanced activity in cisplatin resistant cell lines in comparison to their cis-analogs, indicating that trans-platinum compounds follow some different pattern of antitumor activity in comparison to their cis-isomers. Trans-platinum complexes that have been tested to date and have shown to possess attractive antitumor properties represent diverse group of compounds, and can be classified according to the structure and the nature of nonleaving (amine) ligand as following: trans-ammine(amine) platinum(IV) complexes, trans-platinum(II) complexes with planar ligands, trans-platinum(II) complexes with heterocyclic amine ligands, trans-platinum(II) complexes with iminoether ligands, trans-platinum(II) complexes with asymmetric aliphatic amine ligands, bifunctional binuclear and trinuclear trans-platinum(II) complexes. Potential of trans-platinum complexes to follow some different mechanisms of cell killing in comparison to cis-DDP and thus circumvent cis-DDP resistance, raises interest for their further preclinical evaluation. Keywords: trans-platinum, anticancer drugs, cytotoxicity

High effectiveness of platinum(IV) complex with adamantylamine in overcoming resistance to cisplatin and suppressing proliferation of ovarian cancer cells in vitro

[( OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV)], coded as LA-12, is an octahedral platinum(IV) complex containing a bulky hydrophobic ligand – adamantylamine. The use of bulky hydrophobic amines as non-leaving ligands, may increase uptake of the compound by the cancer cells. Therefore, the effects of LA-12 on sensitive (A2780) and cisplatin resistant (A2780cis) ovarian cancer cell lines were investigated and compared to those of cisplatin. IC 50 and IC 90 concentrations of LA-12 were 6- (A2780) or 18-fold (A2780cis) lower than those for cisplatin (MTT assay). Equitoxic concentrations (IC 50 or IC 90) of both compounds caused a significant and similar time- and dose-dependent inhibition of cell proliferation and an increase in the number of floating cells which corresponded to the decrease of total cell viability. A different type and dynamics of cell cycle perturbation after cisplatin and LA-12 treatment were detected. Exposure to LA-12 resulted in transient accumulation of A2780 and A2780cis cells in S phase, while cisplatin caused G 2/M arrest in sensitive and S phase arrest in resistant cells. A relatively low rate of apoptosis after exposure to IC 50 or IC 90 of both complexes was observed, markedly higher in resistant A2780cis cells. Western blot analysis indicated a concentration-dependent p53 level increase in both lines (higher after cisplatin treatment). PARP cleavage was observed only in A2780cis cells. In conclusion, LA-12 was found to be significantly more efficient than cisplatin, and it was able to overcome the acquired cisplatin resistance (showing resistance factor 2.84-fold lower than those for cisplatin). In spite of the low rate of apoptosis, LA-12 caused increase of p53 level and cell cycle perturbations in the ovarian cancer cell lines studied.

Synthesis and characterization of platinum(II) complexes with 3-methylpiperidine: crystal and molecular structure of [Pt(3-methylpiperidine) 2(malonato)]·H 2O

A series of new platinum complexes of the type [Pt(3-mepip) 2X] (where 3-mepip=3-methylpiperidine, and X=dichloro, sulfato, oxalato, malonato, methylmalonato, dimethylmalonato, tartronato, 1,1-cyclopropanedicarboxylato (CPDCA) or 1,1-cyclobutanedicarboxylato (CBDCA) ligand) were synthesized and characterized by elemental analysis, IR spectroscopy and 195Pt nuclear magnetic resonance spectroscopy. The crystal structure of [Pt(3-mepip) 2(malonato)]·0.79H 2O was determined by single crystal X-ray diffraction. In this complex platinum has slightly distorted square planar geometry with two adjacent corners being occupied by two nitrogens of 3-methylpiperidine, whereas the remaining two adjacent corners are occupied by two oxygen atoms of the malonato group. An intricate network of intermolecular hydrogen bonds holds the crystal lattice together. In the other complexes, 3-mepip acts as non-leaving ligands, whereas the carboxylato ligands act as leaving groups.

Synthesis and characterization of piperidine platinum(II) complexes with dicarboxylates: crystal and molecular structure of cis-[Pt(piperidine) 2Cl 2]·H 2O

A series of new platinum complexes of the type cis-[Pt(PIP) 2X] (where PIP=piperidine and X=dichloro, sulfato, oxalato, malonato, methylmalonato, dimethylmalonato, tartronato, 1,1-cyclopropyldicarboxylato (CPDCA) or 1,1-cyclobutyldicarboxylato (CBDCA) ligand) were synthesized and characterized by elemental analysis, IR, and 195Pt nuclear magnetic resonance spectroscopy. The crystal structure of cis-[Pt(PIP) 2Cl 2]·H 2O was determined by X-ray crystallography. In this complex platinum has slightly distorted square planar geometry with two adjacent corners being occupied by two nitrogen atoms of piperidine, whereas the remaining two adjacent corners are occupied by two chloride atoms. An intricate network of intermolecular hydrogen bonding holds the crystal lattice together. In these complexes, piperidine acts as non-leaving ligand, whereas the dicarboxylic acids act as leaving groups.

Synthesis of 1-(2-aminophenyl)isoquinolines and the biological activity of their cis-dichloro platinum(II) complexes.

The broad biological effects of isoquinolines prompted us to use them as chelating, nonleaving ligands in cis-platinum(II) antitumor complexes. The synthesis of several 1-(2-aminophenyl)isoquinoline derivatives with different levels of hydrogenation and varying substitution of the phenyl ring is reported. These compounds constitute a new class of ligands for the synthesis of oligocyclic platinum(II) complexes. In vitro cytotoxicity tests indicate that the most basic amine ligands afford the most effective complexes. Two of the new complexes were more potent against L1210 murine leukemia cells than the well-established antitumor compound cisplatinum.

Effect of non-leaving ligand environment on aqua ligand substitution in chromium(III) schiff-base complexes

Effect of non-leaving ligand environment on aqua ligand substitution in chromium(III) schiff-base complexes