Methyl Ligands Research Articles

Synthesis, Structure, and Reactivity of a Terminal Cadmium Hydride Compound, [κ3-TismPriBenz]CdH.

The terminal cadmium hydride compound, [κ3-TismPriBenz]CdH, which features the tris[(1-isopropylbenzimidazol-2-yl)dimethylsilyl]methyl ligand, may be obtained via the reactions of either [κ3-TismPriBenz]CdN(SiMe3)2 or [TismPriBenz]CdOSiPh3 with PhSiH3. The Cd-H bond of [κ3-TismPriBenz]CdH undergoes (a) metathesis reactions with MeI, Me3SiX (X = Cl, Br, I, NCO), and Me3SnX (X = Cl, Br, I) to afford the corresponding [TismPriBenz]CdX derivative, (b) insertion with CO2 and CS2 to afford respectively [TismPriBenz]Cd(κ1-O2CH) and [TismPriBenz]Cd(κ1-S2CH), and (c) hydride abstraction with B(C6F5)3 to afford {[TismPriBenz]Cd}[HB(C6F5)3] that possesses a rare trigonal monopyramidal geometry for cadmium.

Synthesis, characterization and electrochemistry of [Pd(PP)MeCl] compounds with 1,1′-bis(phosphino)ferrocene ligands

Three new [Pd(κ2-PP)MeCl] (PP = 1,1′-bis(dicyclohexylphosphino)ferrocene (dcpf), 1-diphenylphosphino-1′-ditert-butylphosphinoferrocene (dppdtbpf) or 1,1ʹ-bis(5-methyl-2-furanylphosphino)ferrocene (dfurpf)) compounds were prepared and characterized. The X-ray crystal structure of [Pd(dppdtbpf)MeCl] was obtained which allowed for unambiguous determination of the cis/trans- relationship between the methyl and chloride ligands with respect to the different phosphine groups. The oxidative electrochemistry of the three new compounds as well as that of the reported [Pd(κ2-PP)MeCl] (PP = 1,1′-bis(diphenylphosphino)ferrocene (dppf), or 1,1′-bis(diiso-propylphosphino)ferrocene (dippf)) and [Pd(κ3-dtbpf)Me]Cl (dtbpf = 1,1′- bis(ditert-butylphosphino)ferrocene) was examined. The compounds with the κ2-bis(phosphino)ferrocene ligands react with sodium tetrakis(3,5-bis(trifluoromethyl)phenylborate) to lose a chloride ligand and the catalytic activity of these compounds was investigated for the polymerization of phenylacetylene.

Ligand Field Inversion as a Mechanism to Gate Bioorganometallic Reactivity: Investigating a Biochemical Model of Acetyl CoA Synthase Using Spectroscopy and Computation.

The biological global carbon cycle is largely regulated through microbial nickel enzymes, including carbon monoxide dehydrogenase (CODH), acetyl coenzyme A synthase (ACS), and methyl coenzyme M reductase (MCR). These systems are suggested to utilize organometallic intermediates during catalysis, though characterization of these species has remained challenging. We have established a mutant of nickel-substituted azurin as a scaffold upon which to develop protein-based models of enzymatic intermediates, including the organometallic states of ACS. In this work, we report the comprehensive investigation of the S = 1/2 Ni-CO and Ni-CH3 states using pulsed EPR spectroscopy and computational techniques. While the Ni-CO state shows conventional metal-ligand interactions and a classical ligand field, the Ni-CH3 hyperfine interactions between the methyl protons and the nickel indicate a closer distance than would be expected for an anionic methyl ligand. Structural analysis instead suggests a near-planar methyl ligand that can be best described as cationic. Consistent with this conclusion, the frontier molecular orbitals of the Ni-CH3 species indicate a ligand-centered LUMO, with a d9 population on the metal center, rather than the d7 population expected for a typical metal-alkyl species generated by oxidative addition. Collectively, these data support the presence of an inverted ligand field configuration for the Ni-CH3 Az species, in which the lowest unoccupied orbital is centered on the ligands rather than the more electropositive metal. These analyses provide the first evidence for an inverted ligand field within a biological system. The functional relevance of the electronic structures of both the Ni-CO and Ni-CH3 species are discussed in the context of native ACS, and an inverted ligand field is proposed as a mechanism by which to gate reactivity both within ACS and in other thiolate-containing metalloenzymes.

The development of novel cytochrome P450 2J2 (CYP2J2) inhibitor and the underlying interaction between inhibitor and CYP2J2

Human Cytochrome P450 2J2 (CYP2J2) as an important metabolic enzyme, plays a crucial role in metabolism of polyunsaturated fatty acids (PUFAs). Elevated levels of CYP2J2 have been associated with various types of cancer, and therefore it serves as a potential drug target. Herein, using a high-throughput screening approach based on enzymic activity of CYP2J2, we rapidly and effectively identified a novel natural inhibitor (Piperine, 9a) with IC50 value of 0.44 μM from 108 common herbal medicines. Next, a series of its derivatives were designed and synthesised based on the underlying interactions of Piperine with CYP2J2. As expected, the much stronger inhibitors 9k and 9l were developed and their inhibition activities increased about 10 folds than Piperine with the IC50 values of 40 and 50 nM, respectively. Additionally, the inhibition kinetics illustrated the competitive inhibition types of 9k and 9l towards CYP2J2, and K i were calculated to be 0.11 and 0.074 μM, respectively. Furthermore, the detailed interaction mechanism towards CYP2J2 was explicated by docking and molecular dynamics, and our results revealed the residue Thr114 and Thr 315 of CYP2J2 were the critical sites of action, moreover the spatial distance between the carbon atom of ligand methylene and Fe atom of iron porphyrin coenzyme was the vital interaction factor towards human CYP2J2.

Half-sandwich organometallic Ru and Rh complexes of (N,N) donor compounds: effect of ligand methylation on solution speciation and anticancer activity

A series of half-sandwich polypyridyl complexes was synthesized and compared focusing on structural, cytotoxic and aqueous solution behaviour. The formula of the synthesized complexes is [M(arene)(N,N)Cl]Cl, where M: Ru or Rh, arene: p-cymene, toluene or C5Me5-, (N,N): 2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (dmb), 1,10-phenanthroline (phen) or 2,9-dimethyl-1,10-phenanthroline (neo). The structures of five half-sandwich complexes were determined by X-ray crystallography. It was found that introducing methyl groups next to the coordinating nitrogen atoms of the bidentate ligand causes steric congestion around the metal centre which changes the angle between ligand planes. The ligands and the Rh complexes showed significant cytotoxicity in A2780 and MES-SA cancer cell lines (IC50 = 0.1-56 μM) and in the cisplatin-resistant A2780cis cells. Paradoxically, phen and dmb as well as their half-sandwich Rh complexes showed increased toxicity against multidrug resistant MES-SA/Dx5 cells. In contrast, coordination to Ru caused loss of toxicity. Solution equilibrium constants showed that the studied metal complexes have high stability, and no dissociation was found for Ru and Rh complexes even at micromolar concentrations in a wide pH range. However, in the case of Ru complexes a slow and irreversible decomposition, namely arene loss, was also observed, which was more pronounced in light exposure in aqueous solution. In the case of neo, the methyl groups next to the nitrogen atoms significantly decrease the stability of complexes. For Rh complexes, the order of the stability constants corrected with ligand basicity (log K*): 9.78 (phen) > 9.01 (dmb) > 8.89 (bpy) > 3.93 (neo). The coordinated neo resulted in an enormous decrease in the chloride ion affinity of Ru compounds. Based on the results, a universal model was introduced for the prediction of chloride ion capability of half-sandwich Rh and Ru complexes. It combines the effects of the bidentate ligand and the M(arene) part using only two terms, performing multilinear regression procedure.

Preparation and crystallographic studies of a new mercuric salicylaldimine complex for fabrication of microscaled and nanoscaled mercuric sulfide as antimicrobial agents against human pathogenic yeasts and filamentous fungi

The new mercuric complex [Hg(HL)2Cl2] incorporating salicylaldimine ligand (HL = 2‐((pyridin‐3‐ylimino)methyl)phenol) was fabricated where the ligand molecules behaved in a monodentate manner via their pyridine nitrogen atoms. In addition to elemental characterization, X‐ray crystallographic studies of the complex revealed its packing in a monoclinic crystal system (space group:I2/a,a= 13.4276(2) Å,b= 6.20950(10) Å,c= 27.7530 (4) Å,α=γ= 90°, andβ= 98.1610(10)°). Hydrothermal treatment of [Hg(HL)2Cl2] with thioacetamide afforded HgS microparticles (HgS μPs; Brunauer–Emmett–Teller [BET] surface area = 6.205 m2/g, diameter = 196.53–259.13 nm, and average size = 213.27 nm), whereas these microparticles were transformed to nanoscaled HgS particles (HgS NPs; BET surface area = 14.380 m2/g, diameter = 58.87–90.56 nm, and average size = 72.78 nm) by the action of ultrasonication. The as‐prepared HgS, HgS NPs in particular, afforded remarkable microbicidal activity against eight strains of filamentous and unicellular human pathogenic fungi and yeasts in comparison with cycloheximide. Remarkably,Aspergillus terreusgrew up to 34.7 ± 1.88 mm in the absence of any fungicide, but HgS μPs, HgS NPs, and cycloheximide limited the fungal growth to 26 ± 0.94, 12.33 ± 1.6, and 28.3 ± 1.7 mm after incubation for 6 days. Besides, inhibition ofRhodotorula glutiniswas of 7.6 ± 0.01 × 107CFU/ml in control sample, but experiments included HgS μPs, HgS NPs, and cycloheximide limited the colony‐forming units ofR. glutinisto 4.2 ± 0.01 × 107, 3.5 ± 0.02 × 107, and 5.9 ± 0.05 × 107CFU/ml.

Preclinical Evaluation of a Novel 99mTc-Labeled CB86 for Rheumatoid Arthritis Imaging.

Early diagnosis and therapy are crucial to control disease progression optimally and achieve a good prognosis in rheumatoid arthritis (RA). Previous study showed that a technetium-99m (99mTc)-labeled TSPO ligand (99mTc-CB256 [2-(8-(2-(bis(pyridin-2-yl)methyl)amino)acetamido)-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide] composed of a translocator protein (TSPO) ligand CB86 [[2-(4-chlorophenyl)-8-amino-imidazo[1,2-a]-pyridin-3-yl]-N,N-di-n-propylacetamide] and di-(2-picolyl)amine, a bifunctional chelate agent, was used to image a TSPO-rich cancer cell in vitro; however, few 99mTc-CB256 in vivo evaluation has been reported so far probably due to the cytotoxicity of CB256 (ca. 75 times more than analogous CB86). Herein, we describe a novel TSPO targeting radiopharmaceutical consisting of CB86 and diethylenetriaminepentaacetic acid (DTPA), a conventional bifunctional chelating ligand in clinical trials used to prepare 99mTc-labeled CB86, and its evaluation as a 99mTc-single-photon emission computed tomography (SPECT) probe. The radiosynthesis and characterization of 99mTc-DPTA-CB86 including hydrophilicity and stability tests were determined. Additionally, the binding affinity and specificity of 99mTc-DTPA-CB86 to TSPO were evaluated using RAW264.7 macrophage cells. Biodistribution and 99mTc-SPECT studies were conducted on rheumatoid arthritis (RA) rat models after the injection of 99mTc-DTPA-CB86 with or without co-injection of unlabeled DTPA-CB86. The radiosynthesis of 99mTc-DTPA-CB86 was completed successfully with the labeling yields and radiochemical purity of 95.86 ± 2.45 and 97.45 ± 0.69%, respectively. The probe displayed good stability in vitro and binding specificity to RAW264.7 macrophage cells. In the biodistribution studies, 99mTc-DTPA-CB86 exhibited rapid inflammatory ankle accumulation. At 180 min after administration, 99mTc-DTPA-CB86 uptakes of the left inflammatory ankle were 2.35 ± 0.10 percentage of the injected radioactivity per gram of tissue (% ID/g), significantly higher than those of the normal tissues. 99mTc-SPECT imaging studies revealed that 99mTc-DTPA-CB86 could clearly identify the left inflammatory ankle with good contrast at 30–180 min after injection. Therefore, 99mTc-DTPA-CB86 may be a promising probe for arthritis 99mTc-SPECT imaging.

Characterization of Cr-Hydrocarbyl Species via Pulse EPR in the Study of Ethylene Tetramerization Catalysis

The characterization of complexes involved in chromium catalysis is challenging due to the paramagnetism of Cr in its common oxidation states. Here, we demonstrate the utility of pulse electron paramagnetic resonance (pulse EPR) techniques in assigning structural features of Cr organometallic complexes relevant to ethylene tetramerization. An S = 3/2, Cr(III) bisaryl-methyl ethylene tetramerization precatalyst (1) has been selected for characterization by CW and pulse EPR spectroscopies. Using an isotopically labeled Cr-CD3 complex (1-d3), the methyl ligand was confirmed to remain bound to Cr in solution by detection of 2H couplings in X-band hyperfine sublevel correlation (HYSCORE) spectroscopy. Protonolysis of 1-d3 led to an S = 3/2, Cr(III) product (2-d3) that maintained spectroscopic features in HYSCORE for the CD3 group, indicative of retention of the Cr-alkyl bond. Following protonolysis of 1-h3 and subsequent reaction with ethylene, an S = 1/2 Cr(I) species with an ethylene-derived ligand was generated, supporting a mechanism involving this Cr oxidation state. Additionally, the pulse EPR characterization of a Cr(I) allyl-diene complex was performed for comparison. This is the first direct observation of hydrocarbyl ligands on Cr using pulse EPR methods. The methods described here are broadly applicable to Cr, first-row transition metals and other open-shell organometallic catalytic systems.

Improving the Stability of EGFR Inhibitor Cobalt(III) Prodrugs.

Although tyrosine kinase inhibitors (TKIs) have revolutionized cancer therapy in the past two decades, severe drawbacks such as strong adverse effects and drug resistance limit their clinical application. Prodrugs represent a valuable approach to overcoming these disadvantages by administration of an inactive drug with tumor-specific activation. We have recently shown that hypoxic prodrug activation is a promising strategy for a cobalt(III) complex bearing a TKI of the epidermal growth factor receptor (EGFR). The aim of this study was the optimization of the physicochemical properties and enhancement of the stability of this compound class. Therefore, we synthesized a series of novel derivatives to investigate the influence of the electron-donating properties of methyl substituents at the metal-chelating moiety of the EGFR inhibitor and/or the ancillary acetylacetonate (acac) ligand. To understand the effect of the different methylations on the redox properties, the newly synthesized complexes were analyzed by cyclic voltammetry and their behavior was studied in the presence of natural low-molecular weight reducing agents. Furthermore, it was proven that reduction to cobalt(II) resulted in a lower stability of the complexes and subsequent release of the coordinated TKI ligand. Moreover, the stability of the cobalt(III) prodrugs was investigated in blood serum as well as in cell culture by diverse cell and molecular biological methods. These analyses revealed that the complexes bearing the methylated acac ligand are characterized by distinctly enhanced stability. Finally, the cytotoxic activity of all new compounds was tested in cell culture under normoxic and various hypoxic conditions, and their prodrug nature could be correlated convincingly with the stability data. In summary, the performed chemical modifications resulted in new cobalt(III) prodrugs with strongly improved stabilities together with retained hypoxia-activatable properties.

One new copper iodide coordination polymer directed by 4-pyridyl dithioether ligand: Syntheses, structures, and photocatalysis

One new compound consisting of 1,1-bis(4-pyridylthio)methylene ([Bpytm]) ligand, namely [Bpytm]CuI (1), has been prepared and characterized by IR spectroscopy, solid Uv-visible diffuse reflectance spectrum, and X-ray Powder Diffraction (PXRD). Compound 1 is a 2D MOF and ligand [Bpytm] coordinate with metal ions to form tetrahedral configuration. For compound 1: Crystal system: Monoclinic, Space group: C2/c, a = 13.6671(11), b = 11.6075(11), c = 17.1225(12), α= 90°, β= 93.707(3)°, γ= 90°, V = 2710.6(4) Å3, Z = 8, Dcalc = 2.082 g cm–3. The photocatalytic properties and thermal stability have been researched.

Water soluble Cu(II) and Zn(II) complexes of bidentate-morpholine based ligand: synthesis, spectral, DFT calculation, biological activities and molecular docking studies

Copper(II) and zinc(II) complexes of the type [ML(AcO)2.H2O] were synthesized from bidentate-morpholine based Schiff base ligand (L - morpholinopropylimino)methyl)-6-methoxyphenol). The prepared ligand, copper(II) and zinc(II) complexes were characterized by elemental analysis, ESI-MS, 1H-NMR, FT-IR, UV-Visible, ESR and spectrometric methods. The elemental and ESI-MS results have been established that the prepared ligand and complexes possess 1:1 stoichiometric ratio. 1H-NMR and FT-IR results have been suggested that azomethine nitrogen and morpholine ring nitrogen atoms are coordinated with Cu(II) and Zn(II) metal ions. UV-Visible, ESI-MS and ESR spectroscopic results have been supported that the proposed structure of Cu(II) and Zn(II) complexes possess square pyramidal geometry. In order to confirm the proposed square pyramidal geometry of prepared complexes by DFT calculation has been studied. DNA binding ability of Cu(II) and Zn(II) complexes have been studied by electronic absorption and viscometric methods. These results reveal that Cu(II) and Zn(II) complexes interact with CT-DNA by the way of groove binding mode. Molecular docking studies result shows that synthesized compounds has better binding ability. The in vitro antioxidant activities of ligand, Cu(II) and Zn(II) complexes have been investigated by using the DPPH assay. The result shows that synthesized compounds have good radical scavenging activity against DPPH radical. Antimicrobial activities of synthesized ligand and its complexes have been tested against selected bacterial (gram positive & gram negative) and fungal species. The results reveal that Cu(II) and Zn(II) have good antimicrobial activity than ligand. Communicated by Ramaswamy H. Sarma

Dynamics and allostery of Zika virus non-structural protein 5 methyltransferase

The methyltransferase (MTase) domain of non-structural protein 5 (NS5) plays a fundamental role in flaviviruses replication, and its inhibition is a strategy for antiviral development. MTase methylates viral RNA cap at guanine N-7 and the ribose 2'OH of the first adenosine. Many structures of Zika virus (ZIKV) and other flaviviruses MTases bound to cofactors, substrates and inhibitor candidates have been solved. Still, the dynamical modulation of MTase binding and catalytic activity yet needs to be clarified. Here, we investigated the structural dynamics of ZIKV NS5 MTase domain free and bound to Guanosine-5'-triphosphate (GTP) and S-Adenosyl-Lmethionine (SAM), to identify the molecular dynamics changes related to ligand binding and methyl transfer reaction. We have observed that the binding of the GTP and SAM individually and GTP-SAM in the ternary complex has induced allostery in the RNA binding site, showing the complexity of ZIKV MTase conformational equilibrium and its impact on viral RNA recognition. We also mapped in molecular dynamics trajectories, conformations of GTP guanine moiety that mimics guanine orientations visualized in human-specific N-methyltransferase structures solved by X-ray crystallography. It is the first time that N-7 methylation-prone guanine orientation has been proposed and modeled in flavivirus MTase. Communicated by Ramaswamy H. Sarma

P-N and N-Mo Bond Formation Processes in the Reactions of a Pyramidal Phosphinidene-Bridged Dimolybdenum Complex with Diazoalkanes and Organic Azides.

The reactivity of the complex [Mo2Cp(μ-κ1:κ1,η5-PC5H4)(CO)2(η6-HMes*)(PMe3)] (1) toward different diazoalkanes and organic azides was investigated. The pyramidal phosphinidene ligand in 1 displayed a strong nucleophilicity, enabling these reactions to proceed rapidly even below room temperature. Thus, 1 reacted rapidly at 253 K with different diazoalkanes N2CRR' (R,R' = H,H, Ph,Ph, H,CO2Et) to give the corresponding P:P-bridged phosphadiazadiene derivatives as major products which, however, could not be isolated. Reaction of the latter with [H(OEt2)2](BAr'4) yielded the corresponding cationic derivatives [Mo2Cp{μ-κ1P:κ1P,η5-P(NHNCRR')C5H4}(η6-HMes*)(CO)2(PMe3)](BAr'4), which were isolated in ca. 70% yield. The related species [Mo2Cp{μ-κ1P:κ1P,η5-P(NMeNCHCO2Et)C5H4}(η6-HMes*)(CO)2(PMe3)](BAr'4) was isolated upon reaction of the ethyl diazoacetate derivative with MeI and subsequent anion exchange with Na(BAr'4). Reaction of 1 with aryl azides (4-C6H4Me)N3 and (4-C6H4F)N3 proceeded rapidly at low temperature to give possibly the corresponding P:P-bridged phosphaimine derivatives as major products, which could be neither isolated. Protonation of these products with [H(OEt2)2](BAr'4) gave the corresponding aminophosphanyl complexes [Mo2Cp{μ-κ1P:κ1P,η5-P(NHR)C5H4}(η6-HMes*)(CO)2(PMe3)](BAr'4), isolated in ca. 75% yield. In contrast, the result of reactions of 1 with benzyl azide was strongly dependent on temperature, including the temperature in the subsequent methylation step that gave isolable cationic derivatives. By a careful choice of experimental conditions, different complexes having methylated phosphatriazadiene ligands were isolated, such as [Mo2Cp{μ-κ1P:κ1P,η5-P(NNNMeCH2Ph)C5H4}(η6-HMes*)(CO)2(PMe3)](BAr'4) and the metallacyclic derivatives syn- and anti-[Mo2Cp{μ-κ2P,N:κ1P,η5-P(NMeNNCH2Ph)C5H4}(η6-HMes*)(CO)(PMe3)](BAr'4). Density functional theory calculations, along with NMR monitoring experiments, revealed that the formation of the latter products stemmed from different and kinetically favored phosphatriazadiene intermediates, thermodynamically disfavored with respect to the denitrogenation process, otherwise yielding phosphaimine derivatives.

New Serotoninergic Ligands Containing Indolic and Methyl Indolic Nuclei: Synthesis and In Vitro Pharmacological Evaluation.

Serotonin is an important biogenic amine and is implicated in wideranging physiological and physiopathological processes. Pharmacological manipulation of the serotoninergic system is believed to have a great therapeutic potential. In order to identify selective ligands for 5-HT1A, 5-HT2A and 5-HT2C receptors two series of 4-substituted piperazine derivatives, bearing indolic or methyl indolic nuclei, were synthesized. All the compounds, synthesized by standard solution methods, were evaluated for 5- HT1A, 5-HT2A and 5-HT2C receptors. The highest affine and selective compounds have been evaluated also on dopaminergic (D1 and D2) and adrenergic (α1A and α2A) receptors. Several of the newly synthesized molecules showed affinity in the nanomolar range for 5- HT1A, 5-HT2A and 5-HT2C receptors and moderate to no affinity for other relevant receptors (D1, D2, α1A and α2A). Compounds 7f and 10a showed a nanomolar affinity towards 5-HT1A with an in vitro pharmacologic profile compatible with antipsychotic drugs.

Stacking interactions of the methylated cyclopentadienyl ligands in the crystal structures of transition metal complexes

In the crystal structures of methylated cyclopentadienyl (Cp) complexes (MeCp, Me4Cp and Me5Cp) deposited in the Cambridge Structural Database, certain orientation types of stacked contacts can be noted as the most frequent. These orientation preferences can be well explained by the matching of oppositely charged regions of electrostatic potential. Parallel displaced stacking, large offset stacking and C-H...π interactions are the dominant interaction types that are responsible for the arrangement in the crystal structures of stacked methylated Cp complexes.

Synthesis, characterization, structures and in vitro antitumor activity of platinum(II) complexes bearing adeninato or methylated adeninato ligands

Reactions of the carbonato platinum(II) complexes [Pt(CO3)(PPh3)2]·CH2Cl2 (1) and [Pt(CO3)(dppe)] (dppe = 1,2-bis(diphenylphosphino)ethane; 2) with adenine (3a) and its N6-methylated derivatives (N6-MeAde, 3b; N6,N6-Me2Ade, 3c) resulted under splitting off carbon dioxide in formation of bis(adeninato)platinum complexes [Pt(N6,N6-RR’Ade–H-κN9)2(PPh3)2] (4a–4c) and [Pt(N6,N6-RR’Ade–H-κN9)2(dppe)] (5a–5c) R/R’ = H, Me, respectively. Analogous reactions with adenines methylated at the N9 or N3 position (9-MeAde, 3d; N6,9-Me2Ade, 3e; 3-MeAde, 3f) gave cationic complexes which could be isolated as hexafluorophosphate salts: [Pt(9-MeAde–H-κ2N6,N7)(PPh3)2][PF6] (6a), [Pt(N6,9-Me2Ade–H-κ2N6,N7)(dppe)][PF6] (6b), and [Pt(3-MeAde–H-κ2N6,N7)(PPh3)2][PF6] (7). The deprotonation of the less acidic exocyclic N6HR (R = H, Me) group and the chelating κ2N6,N7 coordination in complexes 6/7 could unambiguously clarified by 1H,15N HMBC NMR spectroscopy and additionally by DFT calculations. All complexes were fully characterized especially by NMR (1H, 13C, 31P) and single-crystal X-ray structural investigations (4b∙2i-PrOH, 4c, 5a∙MeOH, and 5c∙1.5 MeOH). In vitro antitumoral activity was investigated against five tumor cell lines (A549 lung, A2780 ovarian, DLD-1 colon, FaDu head and neck, and SW1736 anaplastic thyroid). The most active compound 4b was found more active than cisplatin against cisplatin resistant DLD-1 (IC50 = 4.1 ± 0.5 µM) and SW1736 cell lines (IC50 = 1.5 ± 0.4 µM).

Atomic Layer Deposition of Aluminum Phosphate Using AlMe3, PO(OMe)3, and O2 Plasma: Film Growth and Surface Reactions

High purity, uniform, and conformal aluminum phosphate (AlPxOy) thin films were deposited by atomic layer deposition (ALD) between 25 and 300 °C using supercycles consisting of (i) PO(OMe)3 dosing combined with O2 plasma exposure and (ii) AlMe3 dosing followed by O2 plasma exposure. In situ spectroscopic ellipsometry and mass spectrometry were applied to demonstrate the ALD self-limiting behavior and to gain insight into the surface reactions during the precursor and coreactant exposures, respectively. Compared to earlier reported AlPxOy ALD studies using H2O and O3 as coreactants or without using coreactans, the use of an oxygen plasma generally leads to higher growth per cycle values and promotes phosphorus incorporation in the film. Specifically, when using a 1:1 POx:Al2O3 cycle ratio and a substrate temperature of 150 °C, the growth per supercycle is found to be 1.8 A. The [P]:[Al] atomic ratio for this process is approximately 0.5 (∼AlP0.5O2.9) and can be tailored by changing the ratio between the two cycles or the substrate temperature. In literature reports where the same aluminum precursor was used, the [P]:[Al] atomic ratio was limited to 0.2 or a very high number of phosphorus cycles was needed in order to increase the phosphorus content. Instead, we demonstrate deposition of films with a composition close to AlPO4 by using a 2:1 POx:Al2O3 cycle ratio. The limited incorporation of P in the film is suspected to derive from the steric hindrance of the relatively bulky phosphorus precursor. Mass spectrometry suggests that the PO(OMe)3 precursor chemisorbs on the surface without the release of reaction products into the gas phase, whereas Al(Me)3 already undergoes methyl ligand abstraction upon chemisorption.

Co(I) complexes with a tetradentate phenanthroline-based PNNP ligand as a potent new metal-ligand cooperation platform.

A series of low spin cobalt(i) complexes bearing a tetradentate phenanthroline-based PNNP ligand (2,9-bis((diphenylphosphanyl)methyl)-1,10-phenanthroline), [CoCl(PNNP)] (1), [CoMe(PNNP)] (2) and [Co(CH2SiMe3)(PNNP)] (3), were synthesized and structurally identified. Complex 3 underwent a structural rearrangement of the PNNP skeleton upon heating to form [Co(PNNP')] (4), which is supported by an asymmetrical PNNP' ligand with a dearomatized phenanthroline backbone. Mechanistic studies supported that the transformation from 3 to 4 was initiated by the homolysis of either a Co-CH2SiMe3 bond or a benzylic C-H bond. Complex 4 achieved H-H bond cleavage of H2 (1 atm) at ambient temperature, to form [Co(PNNP'')] (6), in which two H atoms were incorporated into the endocyclic double bond of the PNNP'' ligand backbone.

Lanthanides(III) and Silver(I) complex formation with triamines in DMSO: The effect of ligand cyclization

The thermodynamic functions of complexation between lanthanides(III) and 1,4,7-triazacyclononane (TACN) together with those of some of the above metal ions with the TACN-linear-analogue,N′-methyl-N′′-(2-(methylamino)ethyl)ethane-1,2-diamine (DMDIEN), are determined in dimethylsulphoxide (DMSO).The study aims to investigate the effect of ligand cyclization and methylation on the stability and nature of the complexes in non-aqueous solution. The stability constants of Ln3+/TACN complexes were obtained by means of potentiometric titrations at 298 K and I = 0.1 mol dm−3, using Ag+ as competitive ion. Ln3+-ligand complexation enthalpies were obtained by calorimetric titrations, extended also to the silver(I)-TACN system, whose thermodynamic data in DMSO are not published. Calorimetry was applied also to obtain simultaneously enthalpy values and stability constants of the Ln3+/DMDIEN systems, for which the difference in stabilities between Ag+ and Ln3+-DMDIEN complexes did not allow the competitive potentiometric method to work.The Ag+ ion forms mono- and poly-nuclear AgiLji+ complexes with TACN (i:j = 1:1, 1:2 and 2:3), whereas all lanthanide ions form with TACN both 1:1 complexes and 1:2, from Tb3+ to Lu3+. Only 1:1 species were detected for the Ln3+-DMDIEN systems. The 1:1 TACN complexes show an extra stability both with respect to those of DIEN and those of the linear analogue DMDIEN. Negative enthalpies favor the formation of all complexes, while entropies partially counteract the complexation. The results for TACN systems are compared with those here obtained for DMDIEN and for DIEN, reported previously. Density Functional Theory (DFT) calculations, carried out in presence of DMSO introduced as implicit solvent, were performed on some of the Ln3+ complexes with TACN and DIEN to provide insights into the structures and related solvation energies of the species formed in solution. Calculations support a tri-dentate coordination of both ligands. The effects of ligand methylation and cyclization on the stability constants, enthalpies and entropies of complex formation are discussed. The thermodynamic and DFT integrated data indicate that the trends of the thermodynamic functions concerning the complexation reactions of lanthanide ions in DMSO depend on the different solvation of the complexes.

Effect of ligand methylation on the spin-switching properties of surface-supported spin-crossover molecules

X-ray absorption spectroscopy investigations of the spin-state switching of spin-crossover (SCO) complexes adsorbed on a highly-oriented pyrolytic graphite (HOPG) surface have shown so far that HOPG is a promising candidate to realize applications such as spintronic devices because of the stability of SCO complexes on HOPG and the possibility of highly efficient thermal and light-induced spin-state switching. Herein, we present the spin switching of several Fe(II) SCO complexes adsorbed on an HOPG surface with particular emphasis on the thermally induced spin transition behaviour with respect to different structural modifications. The complexes of the type [Fe(bpz)2(L)] (bpz = dihydrobis(pyrazolyl)borate, L = 1,10-phenanthroline, 2,2′-bipyridine) and their methylated derivatives exhibit SCO in the solid state with some differences regarding cooperative effects. However, in the vacuum-deposited thick films on quartz, complete and more gradual spin transition behavior is observable via UV/vis spectroscopy. In contrast to that, all complexes show large differences upon direct contact with HOPG. Whereas the unmodified complexes show thermal and light-induced SCO, the addition of e.g. two or four methyl groups leads to a partial or a complete loss of the SCO on the surface. The angle-dependent measurement of the N K-edge compared to calculations indicates that the complete SCO and HS-locked molecules on the surface exhibit a similar preferential orientation, whereas complexes undergoing an incomplete SCO exhibit a random orientation on the surface. These results are discussed in the light of molecule-substrate interactions.