Half-sandwich Complexes Research Articles

Naphthalene Diimide-Functionalized Half-Sandwich Ru(II) Complexes as Mitochondria-Targeted Anticancer and Antimetastatic Agents.

In this work, four naphthalene diimide (NDI)-functionalized half-sandwich Ru(II) complexes Ru1-Ru4 bearing the general formula [(η6-arene)RuII(N^N)Cl]PF6, where arene = benzene (bn), p-cymene (p-cym), 1,3,5-trimethylbenzene (tmb), and hexamethylbenzene (hmb), have been synthesized and characterized. By introducing the NDI unit into the N,N-chelating ligand of these half-sandwich complexes, the poor luminescent half-sandwich complexes are endowed with excellent emission performance. Besides, modification on the arene ligand of arene-Ru(II) complexes can influence the electron density of the metal center, resulting in great changes in the kinetic properties, catalytic activities in the oxidative conversion of NADH to NAD+, and biological activities of these compounds. Particularly, Ru4 exhibits the highest reactivity and the strongest inhibitory activity against the growth of three tested cancer cell lines. Further study revealed that Ru4 can enter cells quickly in an energy-dependent manner and preferentially accumulate in the mitochondria of MDA-MB-231 cells, inducing cell apoptosis via reactive oxygen species overproduction and mitochondrial dysfunction. Significantly, Ru4 can effectively inhibit the cell migration and invasion. Overall, the complexation with NDI and modification on the arene ligand endowed the half-sandwich Ru(II) complexes with improved spectroscopic properties and anticancer activities, highlighting their potential applications for cancer treatment.

Ni(CO)4 ]+ as NiI Synthon: Synthesis and Characterization of NiI Half-Sandwich and Sandwich Cations.

The stable, easily accessible salt [Ni(CO)4 ]+ [F{Al(ORF )3 }2 ]- (RF =C(CF3 )3 ) was used as a NiI synthon to generate the novel half-sandwich complexes [Ni(arene)(CO)2 ]+ (arene=C6 H6 , o-dfb=1,2-F2 C6 H4 ). By irreversible removal of CO from the equilibrium, even the rather endergonic reaction to a [Ni(o-dfb)2 ]+ salt was successful (Δr G°(solv) =+78 kJ mol-1 ). The latter displays an unprecedented slipped η3 ,η3 -sandwich structure and is the ultimate synthon to NiI -chemistry.

(2,2'-Bipyrid-yl)(η6-p-cymene)iodidoruthenium(II) hexa-fluorido-phosphate.

The title compound, having the mol-ecular formula [RuI(η6-C10H14)(C10H8N2)]PF6, crystallizes in the triclinic P (Z = 2) space group as a half-sandwich complex resembling a three-legged piano stool. Important geometrical parameters include Ru-cymene centroid = 1.6902 (17) Å, Ru-I = 2.6958 (5) Å, [Ru-N]avg = 2.072 (3) Å, N1-Ru-N2 = 76.86 (12)° and a dihedral angle between the planes of the two rings of the bipyridyl system of 5.9 (2)°. The PF6 - ion was treated with a twofold disorder model, refining to a 65.0 (8):35.0 (8) occupancy ratio. The crystal packing features C-H⋯F/I inter-actions.

Occurrence Modes of Critical Metals (Li+ and Ge4+) in the Organic Molecular Structures of Coal: A Density Functional Theory Study.

To explore the mechanism of critical metal (Li+ and Ge4+) occurrence in the organic molecular structures of different rank coals, simulations were investigated using quantum chemical density functional theory. In this paper, Wender lignite, bituminous, and anthracite molecular models were used as organic molecular structures in coal. The electrostatic potential (ESP), frontier molecular orbitals, and Mulliken charges were used to identify adsorption sites in organic molecular structures. Mulliken charge, bond length, Mayer bond order (MBO), and adsorption energy values were used to estimate the binding conformation and strength between organic molecular structures and critical metals (Li+ and Ge4+). The results showed that the negative ESP, the highest occupied molecular orbitals, and negative Mulliken charges in the organic molecular structures were located at the O atom of oxygen functional groups and the aromatic structures, respectively, which were the active sites for critical metal adsorption. Mulliken charge transfer, bond length, MBO, and adsorption energy data suggested that the binding of Li+ with organic molecular structures was controlled by the carbonyl group (C=O), while the aromatic structures had less effect on the occurrence of Li+ in the organic molecular structures. The maximum adsorption energy value for binding Li+ with organic molecular structures was -742.16 kJ/mol. The Ge4+ ions not only showed strong binding ability with oxygen functional groups, but also Ge4+ formed thermodynamically stable half-sandwich complexes with aromatic structures. Therefore, the coal rank had little effect on the binding of Ge4+ with organic molecular structures. Moreover, the binding of Ge4+ with organic molecule structures was enhanced by the synergistic interactions of oxygen functional groups and aromatic structures. The adsorption energy values were up to -8511.43 kJ/mol. The adsorption of organic matter in coal to critical metals (Li+ and Ge4+) generated changes in the spatial configuration of the organic molecular structure, including local twisting of the organic molecular structure in lignite and bending of the aromatic structure in anthracite.

The Indenyl Effect: Accelerated C-H Amidation of Arenes via Ind*RhIII Nitrene Transfer Catalysis.

Investigations into C-H amidation reactions catalysed by cationic half-sandwich d6 metal complexes revealed that the indenyl-derived catalyst [Ind*RhCl2 ]2 significantly accelerated the directed ortho C-H amidation of benzoyl silanes using 1,4,2-dioxazol-5-ones. Ring slippage involving a haptotropic η5 to η3 rearrangement of the indenyl complex proposedly enables ligand substitution at the metal centre to proceed via associative, rather than dissociative pathways, leading to significant rate and yield enhancements. Intriguingly, this phenomenon appears specific for C-H amidation reactions involving weakly coordinating carbonyl-based directing groups with no acceleration observed for the corresponding reactions involving strongly coordinating nitrogen-based directing groups.

Hydroxypyridine/Pyridone Interconversions within Ruthenium Complexes and Their Application in the Catalytic Hydrogenation of CO2

Reaction of a new ligand 6-DiPPon (6-diisopropylphosphino-2-pyridone) with 0.5 equiv of [RuCl2(p-cymene)]2 resulted in the formation of a mixture of [RuCl2(p-cymene)(κ1-P-6-DiPPon)]2 (1) and [RuCl(p-cymene)(κ2-P,N-6-DiPPin)]Cl ([2]Cl) (where 6-DiPPin = 6-diisopropylphosphino-2-hydroxypyridine). The ratio between the two products can be controlled by the nature of the solvent. The similar reaction between 6-DiPPon and [RuCl2(p-cymene)]2 in the presence of AgOTf and Na[BArF24] (where BArF24 = [{3,5-(CF3)2C6H3}4B]-) resulted in the formation of the complexes [RuCl(p-cymene)(κ2-P,N-6-DiPPin)]OTf, ([2]OTf) and [RuCl(p-cymene)(κ2-P,N-6-DiPPin)]BArF24 ([2]BArF24), respectively. Reactions between complex [2]Cl, [2]OTf, or [2]BArF24 and a base (either DBU or NaOMe) resulted in the deprotonation of the hydroxyl functional group to form a novel neutral orange-colored dearomatized complex, 3. The identity of complex 3 was confirmed as [RuCl(p-cymene)(κ2-P,N-6-DiPPon*)], where 6-DiPPon* is the anionic species (6-diisopropylphosphino-2-oxo-pyridinide), which contains the deprotonated moiety. The new 6-DiPPon ligand and its corresponding air stable half-sandwich derivative ruthenium complexes 1, [2]OTf, [2]BArF24, and 3 were all isolated in good yields and fully characterized by spectroscopic and analytical methods. The interconversions between the neutral and anionic forms of the ligands 6-DiPPon, 6-DiPPin, and 6-DiPPon* offer the potential for novel secondary sphere interactions and proton shuttling reactivity. The consequences for this have been explored in the activation of H2 and the subsequent catalytic hydrogenations of CO2 into formate salts in the presence of a base.

Organometallic Ionic Liquids Containing Sandwich Complexes: Molecular Design, Physical Properties, and Chemical Reactivities.

Ionic liquids (ILs) are salts with low melting points and are useful as electrolytes and solvents. We have developed ILs containing cationic metal complexes, which form a family of functional liquids that exhibit unique physical properties and chemical reactivities originating from metal complexes. Our study explores the liquid chemistry in the field of coordination chemistry, where solid-state chemistry is currently the main focus. This review describes the molecular design, physical properties, and reactivities of organometallic ILs containing sandwich or half-sandwich complexes. This paper mainly covers stimuli-responsive ILs, whose magnetic properties, solvent polarities, colors, or structures change by the application of external fields, such as light, heat, and magnetic fields, or by reaction with coordinating molecules.

Half-Sandwich Type Platinum-Group Metal Complexes of C-Glucosaminyl Azines: Synthesis and Antineoplastic and Antimicrobial Activities

While platinum-based compounds such as cisplatin form the backbone of chemotherapy, the use of these compounds is limited by resistance and toxicity, driving the development of novel complexes with cytostatic properties. In this study, we synthesized a set of half-sandwich complexes of platinum-group metal ions (Ru(II), Os(II), Ir(III) and Rh(III)) with an N,N-bidentate ligand comprising a C-glucosaminyl group and a heterocycle, such as pyridine, pyridazine, pyrimidine, pyrazine or quinoline. The sugar-containing ligands themselves are unknown compounds and were obtained by nucleophilic additions of lithiated heterocycles to O-perbenzylated 2-nitro-glucal. Reduction of the adducts and, where necessary, subsequent protecting group manipulations furnished the above C-glucosaminyl heterocycles in their O-perbenzylated, O-perbenzoylated and O-unprotected forms. The derived complexes were tested on A2780 ovarian cancer cells. Pyridine, pyrazine and pyridazine-containing complexes proved to be cytostatic and cytotoxic on A2780 cells, while pyrimidine and quinoline derivatives were inactive. The best complexes contained pyridine as the heterocycle. The metal ion with polyhapto arene/arenyl moiety also impacted on the biological activity of the complexes. Ruthenium complexes with p-cymene and iridium complexes with Cp* had the best performance in ovarian cancer cells, followed by osmium complexes with p-cymene and rhodium complexes with Cp*. Finally, the chemical nature of the protective groups on the hydroxyl groups of the carbohydrate moiety were also key determinants of bioactivity; in particular, O-benzyl groups were superior to O-benzoyl groups. The IC50 values of the complexes were in the low micromolar range, and, importantly, the complexes were less active against primary, untransformed human dermal fibroblasts; however, the anticipated therapeutic window is narrow. The bioactive complexes exerted cytostasis on a set of carcinomas such as cell models of glioblastoma, as well as breast and pancreatic cancers. Furthermore, the same complexes exhibited bacteriostatic properties against multiresistant Gram-positive Staphylococcus aureus and Enterococcus clinical isolates in the low micromolar range.

Proximity-Driven Synergic Copolymerization of Ethylene and Polar Monomers

Coordination copolymerization of ethylene and polar monomers is a promising strategy for preparing structurally well-defined functional polyolefin. However, the poisonous effect of polar groups on employed catalysts is the main obstacle to be overcome. To mimic the synergistic catalysis of multinuclear metal compounds in nature, herein, we report the copolymerization of ethylene with a series of unprotected polar monomers containing oxygen, nitrogen, and sulfur atoms using binuclear half-sandwich scandium complexes C1-Sc2 and C2-Sc2 bearing −CH2– and −CH2CH2– linkers, respectively. In the copolymerization of ethylene and para-methoxystyrene (pMOS), C1-Sc2 and C2-Sc2 exhibit 13 and 7 times greater activities, respectively, than the mononuclear analogue Sc1. For the polar olefins having a butylene spacer, the activities follow the trend C1-Sc2 > C2-Sc2 > Sc1, whereas for the polar olefins that are shorter or longer than the butylene spacer, C2-Sc2 shows the highest activity. Moreover, the synergic effects and the cooperative mechanism for ethylene and pMOS copolymerization with C1-Sc2 were supported by DFT calculations.

Cationic Half-Sandwich Tetrahydrofluorenyl Rare-Earth Metal Complexes as Stable Single-Site Catalysts for (Co)Polymerization of Styrene and Butadiene.

As indenyl-derivates, the tetrahydrofluorenyl ligands had an expanded "wingspan" with considerable steric hindrance. In this text, the rare-earth metal complexes bearing tetrahydrofluorenyl ligands have been synthesized and fully characterized by NMR (1H and 13C) and X-ray diffraction analyses. Upon the activation by [Ph3C][B(C6F5)4], all the scandium complexes exhibited excellent catalytic activity for highly syndioselective polymerization of styrene with a narrow molecular weight distribution (Mw/Mn < 2.0), suggesting the beneficial influence of tetrahydrofluorenyl ligands in stabilizing the single-site active species during the polymerization. Moreover, the scandium-based catalytic systems also promoted the 1,4-regular polymerization of butadiene and its copolymerization with styrene, affording diblock copolymers featuring a highly syndiotactic polystyrene block and a 1,4-specific PBD block. The kinetics investigation revealed the huge gap in TMS-Sc-catalyzed polymerization reactivity ratios (rBD/rSt > 300) between butadiene and styrene, and this further proved the block structure of styrene-butadiene copolymers. The morphology and mechanical property of the selected diblock copolymer were, respectively, investigated by atomic force microscopy and stress-strain experiments.

Nickel-catalyzed cooperative B-H bond activation for hydroboration of N‑heteroarenes, ketones and imines

We report two air-stable nickel(II) half-sandwich complexes, Cp*Ni(1,2-Cy2PC6H4O) (1) and Cp*Ni(1,2-Ph2PC6H4NH) (2), for cooperative B-H bond activation and their applications in catalytic hydroboration of unsaturated organic compounds. Both 1 and 2 react with HBpin by adding the B-H bond across the Ni−X bond (X = O or N), giving rise to the 18-electron Ni(II)−H active species, [H1(Bpin)] and [H2(Bpin)]. Subtle tuning of the Ni−X pair and the supporting ancillary phosphine have a significant effect on the reactivity and catalytic performance of Cp*Ni(1,2-R2PC6H4X). Unlike [H2(Bpin)], the activation of HBpin in [H1(Bpin)] is reversible, which enables the Ni−O complex to be an effective cooperative catalyst in the hydroboration of N-heteroarenes, and as well as ketones and imines.

Interligand Interactions in Half-Sandwich Nickelacarboranes with Phosphine Ligands: Away from Skeletal Rearrangements

Reactions of nickel(II) phosphine complexes [(dppe)NiCl2], [(MePh2P)2NiCl2] and [(Ph3P)2NiCl2] with C-substituted nido-carboranes [7-R-nido-7,8-C2B9H11]− (R = Me, Ph, C(NHCy)2+) were studied. The reactions with [(dppe)NiCl2] lead to the corresponding nickelacarboranes 3,3-(dppe)-1-R-closo-3,1,2-NiC2B9H10 with absent or negligible steric interactions between the ligands. The reactions of [(MePh2P)2NiCl2] with [7-R-nido-7,8-C2B9H11]− (R = H, Me, Ph) result in nickelacarboranes 3,3-(MePh2P)2-1-R-closo-3,1,2-NiC2B9H10 with noticeable steric loading, while the reaction with [7-(CyNH)2C-nido-7,8-C2B9H11] proceeds with the displacement of one phosphine ligand with the formation of a mixed-ligand phosphine-chloride half-sandwich complex 3-MePh2P-3-Cl-1-(CyNH)2C-closo-3,1,2-NiC2B9H10.

Triazine-Augmented Catalytic Activity of Cyclobutadiene Tricarbonyl Fe(0) Complexes for Thermal Decomposition of Ammonium Perchlorate

The employment of combustion catalysts is an effective way to improve ammonium perchlorate (AP) decomposition performance during the combustion process of composite solid propellants. A classic half-sandwich iron carbonyl complex was proposed as the leading structure for exploring high-performance combustion catalysts, in which functionalized cyclobutadienes (Cb) tune the thermal stability and catalytic activity. The thermolysis of Fe2(CO)9 and substituted alkynes initiated [2 + 2] cyclization of alkyne triple bonds and gave η4-cyclobutadiene iron(0) tricarbonyl complexes, CbR1,R2-Fe-CO (1–6), with decent yields. A molecular structure analysis found that the conjugation of the aromatic substituents aryl, ferrocenyl (Fc), and triazinyl (Tz) finely tuned the coordination bonds around the Fe(0) center. The DSC/TG experiments found a remarkable thermal stability of CbTz,R-Fe-CO (3–6) with characteristic thermolysis temperatures (CTT) as high as 500 °C. The catalytic experiments demonstrated that the CTT of Cb-Fe-CO (2-6) overlapped with AP high-temperature decomposition (HTD). The thermal cross-coupling of HTD of AP and CTT of CbTz,Fc-Fe-CO (6) significantly augmented catalytic AP decomposition, resulting in a maximum energy release as high as 2828 J/g.

Half-Sandwich Ruthenium Arene Complexes Bearing Clinically Approved Drugs as Ligands: The Importance of Metal-Drug Synergism in Metallodrug Design.

A novel strategy in metallodrug discovery today is incorporating clinically approved drugs into metal complexes as coordinating ligands. Using this strategy, various drugs have been repurposed to prepare organometallic complexes to overcome the resistance of drugs and to design promising alternatives to currently available metal-based drugs. Notably, the combination of organoruthenium moiety and clinical drug in a single molecule has been shown, in some instances, to enhance pharmacological activity and reduce toxicity in comparison to the parent drug. Thus, for the past two decades, there has been increasing interest in exploiting metal-drug synergism to develop multifunctional organoruthenium drug candidates. Herein, we summarized the recent reports of rationally designed half-sandwich Ru(arene) complexes containing different FDA-approved drugs. This review also focuses on the mode of coordination of drugs, ligand-exchange kinetics, mechanism of action, and structure-activity relationship of organoruthenated complexes containing drugs. We hope this discussion may serve to shed light on future developments in ruthenium-based metallopharmaceuticals.

Exploring alkali metal cation⋯hydrogen interaction in the formation half sandwich complexes with cycloalkanes: a DFT approach

Abstract Gas and solvent phase stability of half sandwich complexes between cycloalkanes viz. cyclopropane, cyclobutane, cyclopentane, cyclohexane, bicyclo[2.2.2]octane and adamantane with alkali metal cations (Li+, Na+ and K+) are analysed using density functional theory (DFT). M06-2X/6-31++G(d,p) level is primarily used for the study. The studied half sandwich complexes are stable in gas phase (stabilization energy upto 26.55 kcal mol−1). Presence of solvent phase irrespective of its dielectric, imparts negative impact on the stability of the chosen complexes. The formation of the complexes is exothermic in nature. The process of complexation is both enthalpy (ΔH) and free energy (ΔG) driven. Variation in HOMO (highest occupied molecular orbital) energy also indicates towards the chemical stability of complexes. The interaction is non-covalent with primary contribution from induction component. NBO analysis indicates that C–H bond is the donor and antibonding metal orbital is the acceptor site in the process of complexation. Stability of the complexes depends on the size of the interacting monomers.

Phosphite Bearing [(μ-ADT)RFe2(CO)6] (ADT = Azadithiolate) Moieties: A Tool for the Building of Multimetallic [FeFe]-Hydrogenase Mimics

A new phosphite ligand having three [(μ-ADT)RFe2(CO)6] (R= p-HOC6H4) moieties (2) has been prepared in good yield by the reaction of complex [(μ-ADT)RFe2(CO)6] (R= p-HOC6H4) 1a with PCl3. Coordination of this phosphite to [PdCl2(MeCN)2] or [PtCl2(DMSO)2] forms heterometallic square planar complexes 5 (C84H48Cl2Fe12N6O42P2MS12) (M = Pt, Pd) in excellent yields. Three-legged piano stool complexes 6 (C52H39Cl2Fe6N3O21PMS6) (M = Rh, Ir) were obtained by the reaction of phosphite 2 with [MCl2Cp*]2 (M = Rh, Ir) in good yields. The formation of complexes 5 and 6 demonstrates the versatility of this new ligand for forming different heteropolymetallic complexes under mild reaction conditions. Moreover, the open-chain derivatives [(μ-ADT)RFe2(CO)6] (R= HOCH2CH2, o-HOC6H4) (1b and 1c, respectively) form cyclic complexes 4 by spontaneous intramolecular CO substitution by the P atom in one of the three [FeFe] fragments. The electrocatalytic behavior of complexes 2 and 4 upon the addition of AcOH is similar to that of related [(μ-ADT)Fe2(CO)6] derivatives. The successive additions of AcOH cause an increase in the current intensity in the wave at about −1.80 V for heteropolymetallic complexes 5 and 6. However, the appearance of a new wave around −1.40 V in complexes 5 points to an acid-promoted side reaction in the electrochemical process.

Ionic mononuclear [Fe] and heterodinuclear [Fe,Ru] bis(diphenylphosphino)alkane complexes: Synthesis, spectroscopy, DFT structures, cytotoxicity, and biomolecular interactions

Iron(II) and Ru(II) half-sandwich compounds encompass some promising pre-clinical anticancer agents whose efficacy may be tuned by structural modification of the coordinated ligands. Here, we combine two such bioactive metal centres in cationic bis(diphenylphosphino)alkane-bridged heterodinuclear [Fe2+, Ru2+] complexes to delineate how ligand structural variations modulate compound cytotoxicity. Specifically, Fe(II) complexes of the type [(η5–C5H5)Fe(CO)2(κ1–PPh2(CH2)nPPh2)]{PF6} (n = 1–5), compounds 1–5, and heterodinuclear [Fe2+, Ru2+] complexes, [(η5–C5H5)Fe(CO)2(μ–PPh2(CH2)nPPh2))(η6–p–cymene)RuCl2]{PF6} (n = 2–5) (compounds 7–10), were synthesized and characterised. The mononuclear complexes were moderately cytotoxic against two ovarian cancer cell lines (A2780 and cisplatin resistant A2780cis) with IC50 values ranging from 2.3 ± 0.5 μM to 9.0 ± 1.4 μM. For 7–10, the cytotoxicity increased with increasing Fe⋅⋅⋅Ru distance, consistent with their DNA affinity. UV–visible spectroscopy suggested the chloride ligands in heterodinuclear 8–10 undergo stepwise substitution by water on the timescale of the DNA interaction experiments, probably affording the species [RuCl(OH2)(η6-p-cymene)(PRPh2)]2+ and [Ru(OH)(OH2)(η6-p-cymene)(PRPh2)]2+ (where PRPh2 has R = [−(CH2)5PPh2–Fe(C5H5)(CO)2]+). One interpretation of the combined DNA-interaction and kinetic data is that the mono(aqua) complex may interact with dsDNA through nucleobase coordination. Heterodinuclear 10 reacts with glutathione (GSH) to form stable mono- and bis(thiolate) adducts, 10-SG and 10-SG2, with no evidence of metal ion reduction (k1 = 1.07 ± 0.17 × 10−1 min−1 and k2 = 6.04 ± 0.59 × 10−3 min−1 at 37 °C). This work highlights the synergistic effect of the Fe2+/Ru2+ centres on both the cytotoxicity and biomolecular interactions of the present heterodinuclear complexes.

Antitumor activity of iridium/ruthenium complexes containing Nitro -substituted quinoline ligands in vivo and in vitro

Four iridium/ruthenium half-sandwich metal complexes containing 8-hydroxyquinoline ligands were synthesized as anticancer agents. In vitro toxicity results showed that all complexes had outstanding antitumor activity against a variety of tumor cells, especially the MDA-MB-231 cell. The complex could initiate downstream apoptotic signals through the lysosomal damage pathway and the reactive oxygen species (ROS) produced at the same time can further aggravate the damage to lysosomes. In addition, the complex significantly inhibited the growth of tumors in the breast cancer mouse xenograft model in vivo.

Mononuclear half-sandwich nd7 metallo drug complexes based on bidentate N∩N dendritic scaffolds: DFT (B3LYP; BP86 and B3PW91) examination

Through an use of three functionals (B3PW91, B3LYP and BP86) associated to a generic basis set LanL2DZ for transition metals (as well as halogen atoms) and 6-311+G (d,p) for others atoms, an examination of the bonding properties of a series of mononuclear half-sandwich nd7 transition metal (anticancer) complexes based on N∩N dendritic scaffolds (L) has been done. Collectively, complexes studied have adopted the piano-stool environment. An examination of the performance of each functional has shown that for the most reliable geometrical analysis of Metal-Nitrogen and Metal-Halogen bonds, the B3LYP and B3PW91 functionalities are suitable respectively. Regardless of the halogen ligand adopted, the B3LYP metal-nitrogen bond lengths are the most widely overestimated. A correlation has been built between the retained charge on each divalent transition metal cation and its metal ion affinity (MIA). Topological examinations reveal the higher instability of metal-N bonds compared to metal-X ones (X = Cl and Br). By the mean of the energy decomposition analysis, a predominant electrostatic character of metal … halogen and [LCP]- … [MX]+ interaction has been demonstrated. The transition metal atom … (hydrophobic) surface (Cp*) interaction is most pronounced for the chloride rhodium complexes of rhodium (combined with (E)-N-(pyridin-2-ylmethylene) Propan-1-amine and 2,2′- dipyridylketone ligands and iridium combined with 2,2′- dipyridylketone ligand. The charge decomposition analysis displays the weakening of the [MLCP*]+−X− bonds in the studied complexes.

Half-Sandwich Rhodium Complexes with Releasable N-Donor Monodentate Ligands: Solution Chemical Properties and the Possibility for Acidosis Activation.

Cancer chemotherapeutics usually have serious side effects. Targeting the special properties of cancer and activation of the anticancer drug in the tumor microenvironment in situ may decrease the intensity of the side effects and improve the efficacy of therapy. In this study, half-sandwich Rh complexes are introduced, which may be activated at the acidic, extracellular pH of the tumor tissue. The synthesis and aqueous stability of mixed-ligand complexes with a general formula of [Rh(η5-Cp*)(N,N/O)(N)]2+/+ are reported, where (N,N/O) indicates bidentate 8-quinolate, ethylenediamine and 1,10-phenanthroline and (N) represents the releasable monodentate ligand with a nitrogen donor atom. UV-visible spectrophotometry, 1H NMR, and pH-potentiometry were used to determine the protonation constants of the monodentate ligands, the proton dissociation constants of the coordinated water molecules in the aqua complexes, and the formation constants of the mixed-ligand complexes. The obtained data were compared to those of the analogous Ru(η6-p-cymene) complexes. The developed mixed-ligand complexes were tested in drug-sensitive and resistant colon cancer cell lines (Colo205 and Colo320, respectively) and in four bacterial strains (Gram-positive and Gram-negative, drug-sensitive, and resistant) at different pH values (5-8). The mixed-ligand complexes with 1-methylimidazole displayed sufficient stability at pH 7.4, and their activation was found in cancer cells with decreasing pH; moreover, the mixed-ligand complexes demonstrated antimicrobial activity in Gram-positive and Gram-negative bacteria, including the resistant MRSA strain. This study proved the viability of incorporating releasable monodentate ligands into mixed-ligand half-sandwich complexes, which is supported by the biological assays.