Potential Metallodrugs Research Articles

Organotin(IV) compounds loaded in thermo- and pH-responsive smart polymeric nanocarriers based on poly(DEGMA-co-OEGMA)-b-poly(DEAEM) a drug releasing system and in vitro anticancer activity

Nanocarriers in cancer treatment are important for transport and release of insoluble drugs. In this work, block thermo- and pH-responsive copolymers based on poly(di(ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) methyl ether methacrylate) (PDO) and poly(2-(N,N-diethylamino)ethyl methacrylate) (PDEA) were tested. At pH 7.4 and 37 °C, the title polymers formed micelles which were used for the loading and release of diorganotin(IV) complexes (LSnR2), where L is a Schiff base ligand and R = n-butyl (LSnBu2) or cyclohexyl (LSnCy2). Results revealed that the PDO-b-PDE block copolymers could enhance the solubility of LSnR2(IV) compounds in PBS at pH = 7.4, resulting in good loading capacity (%DLC) and loading efficiency (%DLE), and better release performance (pH-dependent and T-dependent) than the free compound. In vitro cytotoxic activity was evaluated by the sulforhodamine B (SRB) assay against a normal cell line, African green monkey kidney fibroblast (COS-7) and seven human cancer cell lines prostate (PC-3), leukemia (K-562), colon (HCT-15), lung (SKLU-1), central nervous system glia (U-251), breast Strogen receptor-positive (MCF-7) and breast hormone-independent (MDA-MB-231). The non-loaded block copolymers were non-cytotoxic, but the loaded ones showed high cell growth inhibition against human cancer cell lines. Results confirmed that these temperature and pH-sensitive polymeric systems are excellent candidates for the loading and release of potential metallodrugs, such as LSnR2, against diverse types of cancers.

In-Depth Mass Spectrometry Study of Vanadium(IV) Complexes with Model Peptides.

Investigating the speciation of vanadium complexes in the presence of potential biomolecular targets under physiological conditions remains challenging, and further experimental techniques are needed to better understand the mechanism of action of potential metallodrugs. The interaction of two model peptides (angiotensin I and angiotensin II) with three well-known oxidovanadium(IV) compounds with antidiabetic and/or anticancer activity, [VIVO(pic)2(H2O)], [VIVO(ma)2], and [VIVO(dhp)2] (where pic, ma, and dhp are picolinate, maltolate, and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate anions, respectively), was investigated by ESI-MS/MS (electrospray ionization tandem mass spectrometry) and complemented by EPR (electron paramagnetic resonance) spectroscopy measurements and theoretical calculations at the DFT (density functional theory) level. The results demonstrated that vanadium-peptide bonds are preserved after HCD (higher energy collisional dissociation) fragmentation, allowing for the identification of binding sites through a detailed analysis of the fragmentation spectra. Angiotensin I (AT1) and angiotensin II (AT2) exhibited different coordination behaviors. AT1, with two His residues (His6, His9), prefers to form [AT1 + VOL] adducts with both histidine residues coordinated to the metal ion, while AT2, which has only His6, can bind the metal in a monodentate fashion, forming also [AT2 + VOL2] adducts. Insights from this study pave the way to ESI-MS/MS investigations of more complex systems, including target proteins and further development of vanadium-based drugs.

Effect of ruthenium(II) complexes on MDA-MB-231 cells and lifespan/tumor growth in gld-1mutant, Daf-16 TF and stress productive genes: A perspective study

Pincer type coumarin based N-substituted semicarbazone ligands HL1–4 and their corresponding ruthenium(II) complexes (1–4) were synthesized, analyzed and confirmed by various spectro analytical techniques. The molecular structure of the ligand HL3 and complex 3 was confirmed by single crystal X-ray diffraction analysis. The stoichiometry of complexes 1, 2 and 4 was confirmed by high resolution mass spectroscopy (HRMS). The binding affinity of the compounds with CT-DNA (Calf Thymus DNA) and BSA (Bovine Serum Albumin) was established by absorption and emission titration methods. The results of In vitro cytotoxicity showed the significant cytotoxic potential of the complexes against MDA-MB-231 cells (TNBC- Triple-negative breast cancer). Among the complexes, 1 and 4 have shown appreciable results. Further, antimigratory activity against the MDA-MB-231 cells was studied for the complexes 1 and 4. The percentage cell cycle arrest, apoptosis and necrosis were explored by flow cytometry. The in vivo anti-tumor activity of the complexes 1 and 4 using C. elegans as model organism was established by using the tumoral C. elegans strain JK1466 (gld-1(q485)), which bears a mutation in the gld-1 tumor suppressor gene. We have determined the effect of our complexes on tumor gonad reduction and found to be non toxic to the JK1466 worms and they have prolonged their mean lifespan with potential antioxidant ability by overcoming stress responses. Overall, our study reported herein demonstrated that the complexes 1 and 4 could be established as potential metallo-drugs substantiating further exploration.

Metallomics: An Essential Tool for the Study of Potential Antiparasitic Metallodrugs.

Metallomics is an emerging area of omics approaches that has grown enormously in the past few years. It integrates research related to metals in biological systems, in symbiosis with genomics and proteomics. These omics approaches can provide in-depth insights into the mechanisms of action of potential metallodrugs, including their physiological metabolism and their molecular targets. Herein, we review the most significant advances concerning cellular uptake and subcellular distribution assays of different potential metallodrugs with activity against Trypanosma cruzi, the protozoan parasite that causes Chagas disease, a pressing health problem in high-poverty areas of Latin America. Furthermore, the first multiomics approaches including metallomics, proteomics, and transcriptomics for the comprehensive study of potential metallodrugs with anti-Trypanosoma cruzi activity are described.

Biological Activity of Late Transition Metal‐Based Compounds: From Computational and Theoretical Studies to Laboratory Exploration and Beyond

The use of metal compounds such as cisplatin and its derivatives as therapeutic and diagnostic agents against various diseases is well established. Although metallodrugs have been very successful clinically, low therapeutic selectivity and the potential toxicity of the metal compounds mandate the need for a continuous search for more efficient and specific treatments. Hence, the use of computer‐aided drug design (CADD), molecular modelling and theoretical studies in designing, selecting and applying potential drug candidates have become ever more necessary. Among the many computational and theoretical techniques, molecular docking and density functional theory play significant roles in predicting drug activity. Recent methodologies, within the past 5 years, that rely on these techniques to advance the adoption of potential metallodrugs are highlighted and thoroughly discussed. This is because advancements in computing power have led to the wide use of CADD approaches for drug discovery, development and analysis to shorten the time and reduce the costs associated with drug discovery.

Metallomics as an Essential Analytical Tool for the Development of Potential Metallodrugs

Metallomics as an Essential Analytical Tool for the Development of Potential Metallodrugs

Recent Advances in Bioconjugated Transition Metal Complexes for Cancer Therapy

The introduction of biologically relevant organic moieties in the coordination sphere of transition metal complexes has recently become a well-established strategy to increase the selectivity and biocompatibility of metallodrugs. In this review, the major advances achieved in this area of research in the last three years are described in detail. Particular attention is given to the metal complexes bearing the main biomolecules of life: carbohydrates, lipids, nucleotides, proteins and vitamins. Each paragraph summarizes the synthetic strategy employed to obtain the complexes of interest as well as the most interesting biological results obtained with these potential metallodrugs. Moreover, the structure–activity relationships observed by the different research groups are described and discussed, with the goal of suggesting to the reader the ligand/metal centre combinations that provide the most promising results in the fight against cancer. Some of the compounds examined in this review as well as other bioconjugated metal complexes published in recent decades exhibit interesting selectivity towards cancer cells over normal ones and a specific mode of action. These latter aspects are the basis of what is commonly known as anticancer target therapy.

Antibacterial, antifungal, and anti-biofilm effects of sulfamethoxazole-complexes against pulmonary infection agents.

Antibiotic resistance associated with pulmonary infection agents has become a public health problem, being considered one of the main priorities for immediate resolution. Thus, to increase the therapeutic options in the fight against resistant microorganisms, the synthesis of molecules from pre-existing drugs has shown to be a promising alternative. In this sense, the present work reports the synthesis, characterization, and biological evaluation (against fungal and bacterial agents that cause lung infections) of potential metallodrugs based on sulfamethoxazole complexed with AuI, AgI, HgII, CdII, NiII, and CuII. The minimal inhibitory concentration (MIC) value was used to evaluate the antifungal and antibacterial properties of the compounds. In addition, it was also evaluated the antibiofilm capacity in Pseudomonas aeruginosa, through the quantification of its biomass and visualization using atomic force microscopy. For each case, molecular docking calculations were carried out to suggest the possible biological target of the assayed inorganic complexes. Our results indicated that the novel inorganic complexes are better antibacterial and antifungal than the commercial antibiotic sulfamethoxazole, highlighting the AgI-complex, which was able to inhibit the growth of microorganisms that cause lung diseases with concentrations in the 2-8μgmL-1 range, probably at targeting dihydropteroate synthetase - a key enzyme involved in the folate synthesis. Furthermore, sulfamethoxazole complexes were able to inhibit the formation of bacterial biofilms at significantly lower concentrations than free sulfamethoxazole, probably mainly targeting the active site of LysR-type transcriptional regulator (PqsR). Overall, the present study reports preliminary results that demonstrate the derivatization of sulfamethoxazole with transition metal cations to obtain potential metallodrugs with applications as antimicrobial and antifungal against pulmonary infections, being an alternative for drug-resistant strains.

Interaction of copper potential metallodrugs with TMPRSS2: A comparative study of docking tools and its implications on COVID-19.

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. For the virus to enter the host cell, its spike (S) protein binds to the ACE2 receptor, and the transmembrane protease serine 2 (TMPRSS2) cleaves the binding for the fusion. As part of the research on COVID-19 treatments, several Casiopeina-analogs presented here were looked at as TMPRSS2 inhibitors. Using the DFT and conceptual-DFT methods, it was found that the global reactivity indices of the optimized molecular structures of the inhibitors could be used to predict their pharmacological activity. In addition, molecular docking programs (AutoDock4, Molegro Virtual Docker, and GOLD) were used to find the best potential inhibitors by looking at how they interact with key amino acid residues (His296, Asp 345, and Ser441) in the catalytic triad. The results show that in many cases, at least one of the amino acids in the triad is involved in the interaction. In the best cases, Asp435 interacts with the terminal nitrogen atoms of the side chains in a similar way to inhibitors such as nafamostat, camostat, and gabexate. Since the copper compounds localize just above the catalytic triad, they could stop substrates from getting into it. The binding energies are in the range of other synthetic drugs already on the market. Because serine protease could be an excellent target to stop the virus from getting inside the cell, the analyzed complexes are an excellent place to start looking for new drugs to treat COVID-19.

Mo(VI) Potential Metallodrugs: Explaining the Transport and Cytotoxicity by Chemical Transformations.

The transport and cytotoxicity of molybdenum-based drugs have been explained with the concept of chemical transformation, a very important idea in inorganic medicinal chemistry that is often overlooked in the interpretation of the biological activity of metal-containing systems. Two monomeric, [MoO2(L1)(MeOH)] (1) and [MoO2(L2)(EtOH)] (2), and two mixed-ligand dimeric MoVIO2 species, [{MoO2(L1-2)}2(μ-4,4'-bipy)] (3-4), were synthesized and characterized. The structures of the solid complexes were solved through SC-XRD, while their transformation in water was clarified by UV-vis, ESI-MS, and DFT. In aqueous solution, 1-4 lead to the penta-coordinated [MoO2(L1-2)] active species after the release of the solvent molecule (1 and 2) or removal of the 4,4'-bipy bridge (3 and 4). [MoO2(L1-2)] are stable in solution and react with neither serum bioligand nor cellular reductants. The binding affinity of 1-4 toward HSA and DNA were evaluated through analytical and computational methods and in both cases a non-covalent interaction is expected. Furthermore, the in vitro cytotoxicity of the complexes was also determined and flow cytometry analysis showed the apoptotic death of the cancer cells. Interestingly, μ-4,4'-bipy bridged complexes 3 and 4 were found to be more active than monomeric 1 and 2, due to the mixture of species generated, that is [MoO2(L1-2)] and the cytotoxic 4,4'-bipy released after their dissociation. Since in the cytosol neither the reduction of MoVI to MoV/IV takes place nor the production of reactive oxygen species (ROS) through Fenton-like reactions of 1-4 with H2O2 occurs, the mechanism of cytotoxicity should be attributable to the direct interaction with DNA that happens with a minor-groove binding which results in cell death through an apoptotic mechanism.

Na, K-ATPase as a Biological Target for Gold(III) Complexes: A Theoretical and Experimental Approach.

Gold-based complexes represent a new class of potential metallodrugs. Although their action mechanism is not entirely understood, it was shown that gold complexes inhibit some enzymes' activities. Among them, Na,K-ATPase is emerging as an essential target for various anticancer drugs. The functionalization of nanoparticles by gold(III) complexes could facilitate their delivery into the cells and enable the following of their distribution in the target tissues. The paper presents an overview of Na,K-ATPase interaction with representative and structurally related cytotoxic gold(III) complexes. The results obtained by the employment of theoretical methods (DFT and docking studies) combined with the experimental approach involving a variety of nanotechnology-base techniques (UV/Vis, Raman and fluorescence spectroscopy, CD, AFM, DLS) are discussed. Detailed information was obtained on the enzyme's conformational and structural changes upon binding the gold(III) complexes. The experimentally determined reaction parameters (constants of dissociation and the reaction stoichiometry) were predicted theoretically. The presented results offer further support to the view that Na,K-ATPase may be a relevant biomolecular target for cytotoxic gold(III) compounds of medicinal interest.

Unveiling VIV O2+ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic-Computational Approach.

Human serum albumin (HSA) is involved in the transport of metal ions and potential metallodrugs. Depending on the metal, several sites are available, among which are N-terminal (NTS) and multi-metal binding sites (MBS). Despite the large number of X-ray determinations for albumins, only one structure with Zn2+ is available. In this work, the binding to HSA of the VIV O2+ ion was studied by an integrated approach based on spectroscopic and computational methods, which allowed the systems to be characterized even in the absence of X-ray analysis. The behavior depends on the type of albumin, defatted (HSAd ) or fatted (HSAf ). With HSAd 'primary' and 'secondary' sites were revealed, NTS with (His3, His9, Asp13, Asp255) and MBS with (His67, His247, Asp249, Asn99 or H2 O); with increasing the ratio VIV O2+ /HSAd , 'tertiary' sites, with one His-N and other donors (Asp/Glu-O or carbonyl-O) are populated. With HSAf , fatty acids (FAs) cause a rotation of the subdomains IA and IIA, which results in the formation of a dinuclear ferromagnetic adduct (VIV O)2 D (HSAf ) with a μ1,1 -Asp249 and the binding of His247, Glu100, Glu252, and His67 or Asn99. FAs hinder also the binding of VIV O2+ to the MBS.

Ruthenacarborane-Phenanthroline Derivatives as Potential Metallodrugs.

Ruthenium-based complexes have received much interest as potential metallodrugs. In this work, four RuII complexes bearing a dicarbollide moiety, a carbonyl ligand, and a phenanthroline-based ligand were synthesized and characterized, including single crystal diffraction analysis of compounds 2, 4, and 5 and an observed side product SP1. Complexes 2–5 are air and moisture stable under ambient conditions. They show excellent solubility in organic solvents, but low solubility in water.

Regulation of the aggregation behavior of human islet amyloid polypeptide fragment by titanocene complexes.

The aggregation of human islet amyloid polypeptide (hIAPP) is associated with type II diabetes. The misfolding of hIAPP induces amyloid deposition and causes β-cell dysfunction. Metal complexes are potential metallodrugs that may reverse the aggregation of amyloid peptides. hIAPP19-37 is a crucial fragment of the full-length hIAPP1-37 and contains typical aromatic residues and a core hydrophobic region. In this work, we studied the effects of titanocene complexes titanocene dichloride (1), titanocene salicylic acid complex (2), and titanocene methionine complex (3) on the aggregation behavior of hIAPP19-37. We also explored the possible interactions of these complexes with hIAPP19-37. Results demonstrated that the titanocene complexes could effectively inhibit the aggregation of hIAPP19-37. The complexes bound with hIAPP19-37 in a spontaneous and exothermic process through hydrophobic interaction. Moreover, complex 3 could significantly decrease the cytotoxicity of hIAPP19-37 and improve cell survival. These data provide a basis for the use of titanocene complexes as potential agents against amyloidosis.

Disaggregation of human islet amyloid polypeptide fibril formation by ruthenium polypyridyl complexes

The toxicity of amyloid proteins is associated with many degenerative and systematic diseases. The aggregation of human islet amyloid polypeptide may induce pancreatic β-cell death, which is linked to type II diabetes. Ruthenium complexes are inhibitors of various proteins and potential anticancer metallodrugs, which can also be used to disaggregate amyloid proteins. This work reported that several ruthenium polypyridyl complexes remarkably affected the peptide aggregation by predominant hydrophobic interaction and metal coordination, as reflected by thermodynamic parameters and mass spectrometry analysis. Morphology and particle size analysis showed that the amyloid fibrils were disaggregated from long fibrils into small nano particles. Addition of these complexes also decreased the cytotoxicity induced by the peptide. The results indicated that ruthenium polypyridyl complexes may be potential metallodrugs to treat amyloidosis.

Zinc complexes of diflunisal: Synthesis, characterization, structure, antioxidant activity, and in vitro and in silico study of the interaction with DNA and albumins

From the reaction of ZnCl2 with the non-steroidal anti-inflammatory drug diflunisal (Hdifl), complex [Zn(difl-O)2(MeOH)4], 1 was formed, while in the presence of a N,N′-donor heterocyclic ligand 2,2′-bipyridylamine (bipyam), 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen) and 2,2′-dipyridylketone oxime (Hpko), the complexes [Zn(difl-O,O')2(bipyam)], 2, [Zn(difl-O,O′)2(bipy)], 3, [Zn(difl-O,O′)2(phen)], 4 and [Zn(difl-O)2(Hpko)2], 5 were isolated, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes 2, 3 and 5 were determined by X-ray crystallography. The ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals and to inhibit soybean lipoxygenase was studied and the complexes were more active than free Hdifl. The interaction of the complexes with serum albumins was monitored by fluorescence emission spectroscopy and the corresponding binding constants were calculated. UV–vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide were employed to investigate the interaction of the complexes with calf-thymus DNA and revealed intercalation as the most possible DNA-binding mode. Computational techniques were used to identify possible binding sites of albumins and DNA, and determine the druggability of human and bovine serum albumins with the five novel complexes. The majority of the complexes are stronger binders than the free Hdifl. This is the first study incorporating experimental and computational results to explore the binding activity of metal-NSAID complexes with DNA and serum albumins, suggesting their application as potential metallodrugs.

Effects of ruthenium complexes on prion amyloid peptide PrP115-135 aggregation and their interaction mechanism

Protein conformational change and amyloid fibrils deposition are associated with severe diseases. Those proteins include amyloid- β protein (A β , Alzheimer’s disease), human islet amyloid polypeptide (hIAPP, type 2 diabetes mellitus, T2DM), and prion protein (PrP, transmissible spongiform encephalopathies). Scientists have focused on studying these amyloid proteins to develop potential drugs against the diseases. Prion disease is a type of chronic progressive fatal neurodegenerative disease, whose pathogenic mechanism is the conformational conversion of normal prion protein PrPC to a pathogenic type PrPSc. The transition produces amyloid deposition and consequent neurotoxicity. PrP115-135 (115-AAAAGAVVGGLGGYMLGSAMS-135) is an N-terminal fragment of PrP with self-aggregation and cytotoxicity. Metal complexes act as traditional antitumor agents, and non-platinum-based metallodrugs are developed to improve clinical effectiveness in terms of their general toxicity and spectral activity. Besides, they interact with various proteins, enzymes and bioactive peptides. Ruthenium complexes can effectively bind to proteins, such as apotransferrin, apolactoferrin, and serum albumin, resulting in the altered protein structure and binding ability toward other molecules. They are also considered as potential inhibitors of amyloid proteins because of their low cytotoxicity and disaggregation ability to amyloid fibrils. This work studied the interactions of PrP115-135 with two ruthenium complexes NAMI-A and KP418 in order to compare the action mechanisms between different prion neuropeptides and ruthenium complexes. The intrinsic fluorescence method and cyclic voltammetry (CV) were used to study the binding mode and binding affinity of the two complexes to PrP15-135. In addition, we used Thioflavin T fluorescence assay to display the effects of ruthenium complexes on amyloid peptide aggregation. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to reveal the effects of ruthenium complexes on amyloid peptide-induced cytotoxicity. The change in peptide fluorescence upon metal complex addition could be assumed to reflect the amounts of peptide–ruthenium complex produced and the conformational change of the peptide. The dissociation constant K d values were (6.2±1.4) and (6.4±1.1) μ mol/L for KP418 and NAMI-A respectively, indicating a strong binding affinity between the peptide and ruthenium complexes. CV method showed that, the reduction potential of the complexes changed with the addition of the peptide, reducing the peak current as well. The change of reduction potential indicated that the interaction between them was attributed to electrostatic interaction, and the decrease of the reduction peak current implied that there were other binding forces, such as hydrophobic interaction existed. ThT assay showed that, after incubating ruthenium complexes with aggregated PrP115-135, the fluorescence intensity decreased dramatically. It suggested that the two complexes effectively inhibited the aggregation of peptide. The aggregation kinetics indicated that the complex could significantly prolong the nucleation period and aggregation time of amyloid peptide. Ruthenium complexes could bind to PrP115-135 and inhibit their aggregation, forming oligomers or monomers, thereby reducing the cytotoxicity of PrP115-135 and improving the survival rate of cells. The inhibitory effect of the two complexes on the aggregation of PrP115-135, and their rescue of peptide induced cytotoxicity make it possible for them to be inhibitors of peptide aggregation and potential drugs against amyloidosis. Exploring metal complexes with low toxicity, better disaggregation ability and good water solubility that can penetrate the blood-brain barrier is a principal research direction in this field. So our next step will keep on configuration design of the complexes so as to find potential metallodrugs against prion disease.

Platinum(ii) O,S complexes as potential metallodrugs against Cisplatin resistance.

We report on platinum(ii) complexes with different cinnamic acid derivatives as ligands with cytotoxic activity against Cisplatin resistant ovarian cancer cell line subcultures of SKOV3 and A2780. A typical mechanism of action for platinum(ii) complexes as Cisplatin itself is binding to the DNA and inducing double-strand breaks. We examined the biological behavior of these potential drugs with 9-methylguanine using NMR spectroscopic methods and their DNA damage potential including γH2AX-foci analyses. X-ray diffraction methods have been used to elucidate the molecular structures of the platinum(ii) complexes. Interactions with the model protein lysozyme have been evaluated by different techniques including UV-Vis absorption spectroscopy, fluorescence and X-ray crystallography.

Organometallic complexes of (thio)allomaltol-based Mannich-products: Synthesis, stability and preliminary biological investigations

Organometallic complexes with (thio)pyrone-based ligands have been shown to possess promising cytotoxic properties. To extend the class of potential metallodrugs, the (thio)pyrone backbone was modified via Mannich reaction with morpholine, N-methylpiperazine and piperidine as cyclic amine. The ligands and organometallic complexes were characterized by means of 1D and 2D NMR, ESI MS and also in one case by X-ray diffraction analysis. Due to the high aqueous solubility, the behavior and stability in aqueous solution of the synthesized complexes was studied by 1H NMR spectroscopy. In addition, the influence of these modifications on cytotoxicity in human cancer cell lines was investigated by means of the MTT assay.

Microwave-assisted synthesis of N-heterocycle-based organometallics

A series of 15 different metal-arene-complexes of the general formula [M(arene)(azole)2Cl]Cl and [M(arene)(azole)Cl2], where M = Ru (1–4), Os (5–8), Rh (9–12) or Ir (13–15), arene = η6-p-cymene or 1,2,3,4,5-pentamethylcyclopentadienyl and azole = 1-Me-imidazole, 1H-pyrazole, 1H-benzimidazole or morpholine, has been synthesized under microwave conditions. The reaction time was dramatically reduced from several hours to a few minutes, accompanied by smaller solvent amounts and - in some cases - an increased yield. The organometallic complexes have been characterized by standard analytical methods, the reaction conditions have been optimized and the solid state structures of several examples are reported. The obtained organometallic complexes can be utilized as building blocks for potential metallodrugs or catalysts.