Multinuclear NMR Studies Research Articles

Stable and Inert Yttrium(III) Complexes with Pyclen-Based Ligands Bearing Pendant Picolinate Arms: Toward New Pharmaceuticals for β-Radiotherapy.

We report the synthesis of two azaligands based on the pyclen macrocyclic platform containing two picolinate and one acetate pendant arms. The two ligands differ in the relative positions of the pendant functions, which are arranged either in a symmetrical (L3) or nonsymmetrical (L4) fashion. The complexation properties of the ligands toward natY3+ and 90Y3+ were investigated to assess their potential as chelating units for radiopharmaceutical applications. The X-ray structures of the YL3 and YL4 complexes show nonadentate binding of the ligand to the metal ions. A multinuclear 1H, 13C, and 89Y NMR study shows that the complexes present a structure in solution similar to that observed in the solid state. The two complexes present very high thermodynamic stability constants (log KYL = 23.36(2) and 23.07(2) for YL3 and YL4, respectively). The complexes also show a remarkable inertness with respect to their proton-assisted dissociation, especially YL4. 90Y radiolabeling was proved to be efficient under mild conditions. The 90YL3 and 90YL4 radiochelates were found to be more stable than 90Y(DOTA).

Mechanistic Studies on the Catalytic Synthesis of BN Heterocycles (1H-2,1-Benzazaboroles) at Ruthenium

We had recently disclosed a catalyzed transformation toward the synthesis of BN molecules under an H2 atmosphere under mild conditions. We now report an in-depth mechanistic study to understand how a substrate featuring two different functional groups, C≡N and B–H, namely the 2-cyanophenyl(amino)borane HB(NiPr2)C6H4(CN) (2), can be transformed into the BN heterocycle 1H-2,1-benzazaborole (3). Such a complex transformation has direct links with three key important processes: hydrogenation of nitriles, hydroboration of polar bonds, and B–N bond formation. A combination of in situ monitoring of the catalytic reaction, stoichiometric experiments, and variable-temperature multinuclear NMR and DFT studies allowed us to decipher the catalytic cycle. We show that the catalyst precursor [RuH2(η2-H2)2(PCy3)2] (1) is regenerated at the end of the transformation. We intercepted the transformation of the starting substrate 2, in the form of a 1H-2,1-benzazaborolyl ligand coordinated to the metal center by the formed B...

Multinuclear (Sn/Pd) complexes with disodium 2,2′-(dithiocarboxyazanediyl)diacetate hydrate; Synthesis, characterization and biological activities

Bimetallic chlorodi-/triorganotin(IV) derivatives of general formulas R2(H2O)SnLCSSSn(Cl)R2 (R=Me: 1; Ph: 2) and R3Sn(Na)LCSSSnR3·H2O (R=Bu: 3; Ph: 4) were prepared by reaction of iminodiacetic acid disodium salt hydrate (Na2LH) with CS2 and R2SnCl2/R3SnCl in methanol. The reaction between Na2LH, CS2, and PdCl2 produced [Na2LCSS]2Pd·2H2O (5) which was treated with R3SnCl to synthesize the heterobimetallic derivatives [R3Sn(Na)LCSS]2Pd·2H2O (R=Me: 6; Ph: 7). The complexes were characterized by microanalysis, spectroscopic, and thermogravimetric analyses. Elemental analysis data, mass fragmentation, and thermal degradation patterns supported the molecular composition of the complexes. FT-IR data indicated monodentate binding of carboxylate while a chelating coordination mode of the dithiocarboxylate was verified in the solid state. A five-coordinate tin(IV) was demonstrated in the solid state. In solution, a tetrahedral/trigonal bipyramidal configuration around Sn(IV) and a square planar geometry of Pd(II) was indicated by multinuclear NMR (1H and 13C) and UV-visible studies. The Pd(II) derivatives showed interaction with salmon sperm-DNA and caused an inhibition of alkaline phosphatase (ALPs). The antibacterial/antifungal potential of the coordination products varied with the nature of incorporated metal and a substitution pattern at tin(IV); the palladium metallation decreased the antimicrobial activities. The triorganotin(IV) products exhibited more powerful action against bacteria/fungi as compared to their diorganotin(IV) counterparts. The complexes displayed sufficiently lower hemolytic effects in vitro as compared to triton X-100 and slightly higher than PBS.

Investigations of LiP(SiMe2CH2SiMe3)–PtBu2, the Surprising Byproduct in the Metalation of (Me3Si)2P–PtBu2

During the metalation reaction of (Me3Si)2P–PtBu2 with nBuLi, a byproduct with the sum formula Li(thf)nP(SiMe2CH2SiMe3)–PtBu2 (2, n = 2.7–1) was detected. The formation of the unexpected substituent SiMe2CH2SiMe3 was investigated, a possible reaction mechanism based on DFT calculations established, and the compound synthesized following an independent route. Compound 2 eliminated thf in vacuo to yield the dimeric [Li(thf)P(SiMe2CH2SiMe3)–PtBu2]2 (2a). Exchange of thf with tmeda [Me2N(CH2)2NMe2] in 2 led to the solvent‐separated ion pair [Li(tmeda)2]+[(SiMe2CH2SiMe3)P–PtBu2]– (4). The solid‐state structures of 2a, 4, and the contact ion pair Li(thf)(tmeda)P(SiMe2CH2SiMe3)–PtBu2 (5) were determined by single‐crystal X‐ray diffraction analysis. Extensive variable‐temperature multinuclear NMR studies were carried out to elucidate the structures of these compounds in solution and to compare them with the solid‐state structures.

Multinuclear NMR and diffusion studies of quaternary amine-based ionic liquids.

Multinuclear NMR and diffusion studies of quaternary amine-based ionic liquids.

Gallium(III) chelates of mixed phosphonate-carboxylate triazamacrocyclic ligands relevant to nuclear medicine: Structural, stability and in vivo studies

Three triaza macrocyclic ligands, H6NOTP (1,4,7-triazacyclononane-N,N′,N″-trimethylene phosphonic acid), H4NO2AP (1,4,7-triazacyclononane-N-methylenephosphonic acid-N′,N″-dimethylenecarboxylic acid), and H5NOA2P (1,4,7-triazacyclononane-N,N′-bis(methylenephosphonic acid)-N″-methylene carboxylic acid), and their gallium(III) chelates were studied in view of their potential interest as scintigraphic and PET (Positron Emission Tomography) imaging agents. A 1H, 31P and 71Ga multinuclear NMR study gave an insight on the structure, internal dynamics and stability of the chelates in aqueous solution. In particular, the analysis of 71Ga NMR spectra gave information on the symmetry of the Ga3+ coordination sphere and the stability of the chelates towards hydrolysis. The 31P NMR spectra afforded information on the protonation of the non-coordinated oxygen atoms from the pendant phosphonate groups and on the number of species in solution. The 1H NMR spectra allowed the analysis of the structure and the number of species in solution.31P and 1H NMR titrations combined with potentiometry afforded the measurement of the protonation constants (log KHi) and the microscopic protonation scheme of the triaza macrocyclic ligands. The remarkably high thermodynamic stability constant (log KGaL=34.44 (0.04) and stepwise protonation constants of Ga(NOA2P)2− were determined by potentiometry and 69Ga and 31P NMR titrations. Biodistribution and gamma imaging studies have been performed on Wistar rats using the radiolabeled 67Ga(NO2AP)− and 67Ga(NOA2P)2−chelates, having both demonstrated to have renal excretion. The correlation of the molecular properties of the chelates with their pharmacokinetic properties has been analysed.

Employing a neutral “PN3P” pincer to access mer-Re(I) tricarbonyl complexes: Autoionization of a halo ligand and the role of an N-R (R = H, Me) substituent

A series of monovalent Re complexes, mer-[Re{κ3-2,6-(Ph2PNH)2NC5H3}(CO)3]+, cis-[Re{κ3-2,6-(Ph2PNMe)2NC5H3}(CO)2Cl], and mer-[Re{κ3-2,6-(Ph2PNMe)2NC5H3}(CO)3]+ supported by neutral “PN3P” ligands have been synthesized by addition of pincer ligand to Re(CO)5X (X=Cl, Br). The products were characterized by multinuclear NMR and single crystal X-ray diffraction studies and showed a dependence on the identity of the halo ligand in starting material and on the substitution pattern of the pincer ligand. The formation of the mer-Re(CO)3 core geometry and the autoionization of halide ligand in the majority of these species is in marked contrast to the bulk of the literature on the substitution chemistry of Re(I) carbonyl halides.

Synthesis and characterisation of new perfluoropropenyl complexes of gold, platinum, palladium, and titanium

The new stable perfluoropropenyl organometallic complexes [(Ph3P)Au(E-CF=CFCF3)], trans-[(Ph3P)2Pt(Z-CF=CFCF3)Cl], trans-[(Ph3P)2Pd(E-CF=CFCF3)Cl], [(COD)Pt(E-CF=CFCF3)2] and [Cp2Ti(E-CF=CFCF3)Cl] have been obtained from the reaction of LiCF=CFCF3–derived from Z-CFH=CFCF3 (HFC-1225ye) – with appropriate transition-metal starting materials. The complexes have been characterized by multinuclear NMR studies (19F,1H, 31P and 13C) and single-crystal structure determinations. Based on the X-ray derived data a comparison is made between σ-bound perfluoropropenyl and perfluorovinyl ligands; whilst they are found to be electronically quite similar on the basis of their trans-influence the perfluoropropenyl group is significantly more sterically-demanding, and it is suggested that this accounts for the predominance of mono-perfluoropropenyl-substituted complexes with enhanced stabilities.

Speciation and Multinuclear NMR Spectroscopic Studies of Di- and Trimethyltin(IV) Moieties with MESNA in Aqueous Medium

The interaction of Me2Sn(IV)2+ and Me3Sn(IV)+ with a prodrug, sodium 2-mercaptoethane sulfonate (HSCH2CH2SO3Na, MESNA) abbreviated as (HL), has been studied potentiometrically in aqueous solution (I = 0.1 mol·L−1 KNO3, 298 K). The concentration distribution of various species formed in the solution was studied with changes in pH (~3–11). A strong coordination of MESNA with metal through the S atom of thiol group has been found. In the Me2Sn(IV)–HL system, the species [Me2Sn(L)]+ (53.1–75.6%) is predominant at acidic pH (3.73 ± 0.02) and the species [Me2Sn(L)2OH]− (29.4–38.5%) is predominant at basic pH (10.32 ± 0.08). In contrast, for the Me3Sn(IV)+ system, [Me3SnL] (37.0–57.4%) is the major species at pH 7.65 ± 0.03 and [Me3Sn(OH)] (49.9–67.2%) and [Me3Sn(L)(OH)]− (30.2–46.5%) are the major species at pH 11.05 ± 0.01. However, at physiological pH (7.01 ± 0.32), in both (1:1) and (1:2) Me2Sn(IV)–HL systems, the species [Me2Sn(L)(OH)] (67.2–89.9%) is predominant, whereas for Me3Sn(IV)–HL (1:1) and (1:2) systems, [Me3Sn(OH)] (53.5%) and [Me3SnL] (56.8%) are the respective predominant species. In order to characterize the possible geometry of the proposed complex species, multinuclear (1H, 13C and 119Sn) NMR studies were carried out at different pHs. No polymeric species were detected in the experimental pH range.

Multinuclear NMR Study of the Solid Electrolyte Interface Formed in Lithium Metal Batteries.

The composition of the solid electrolyte interphase (SEI) layers formed in Cu|Li cells using lithium bis(fluorosulfonyi)imide (LiFSI) and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in 1,2-dimethoxyethane (DME) electrolytes is determined by a multinuclear solid-state MAS NMR study at high magnetic field. It is found that the "dead" metallic Li is largely reduced in the SEI layers formed in a 4 M LiFSI-DME electrolyte system compared with those formed in a 1 M LiFSI-DME electrolyte system. This finding relates directly to the safety of Li metal batteries, as one of the main safety concerns for these batteries is associated with the "dead" metallic Li formed after long-term cycling. It is also found that a large amount of LiF, which exhibits superior mechanical strength and good Li+ ionic conductivity, is observed in the SEI layer formed in the concentrated 4 M LiFSI-DME and 3 M LiTFSI-DME systems but not in the diluted 1 M LiFSI-DME system. Quantitative 6Li MAS NMR results indicate that the SEI associated with the 4 M LiFSI-DME electrolyte is denser than those formed in the 1 M LiFSI-DME and 3 M LiTFSI-DME systems. These studies reveal the fundamental mechanisms behind the excellent electrochemical performance associated with higher concentration LiFSI-DME electrolyte systems.

A Multinuclear NMR Study of Six Forms of AlPO-34: Structure and Motional Broadening

We report a study of the CHA-type aluminophosphate AlPO-34, prepared with six different structure-directing agents (SDAs): piperidine (pip), morpholine (mor), pyridine (pyr), 1,4,8,11-tetraazacyclotetradecane (cyclam), 1,3-dimethylimidazolium (dmim) chloride, and 1-ethyl-3-methylimidazolium (emim) bromide. Using a combination of solid-state NMR spectroscopy, periodic density functional theory (DFT) calculations, and synchrotron X-ray diffraction, we show that, even in crystallographically well-ordered materials such as AlPO-34 with dmim as the SDA, local disorder may be present. For such disordered structures, where it is challenging to use DFT to assign NMR spectra, we show that the 31P isotropic chemical shift can be predicted accurately using the mean P–O bond length and P–O–Al bond angle, in an extension of previous work. Variable-temperature 27Al NMR reveals the presence of microsecond-time scale dynamics in all forms of AlPO-34, with two different motional regimes observed, depending on whether stru...

Study on the Acid-Induced Ring-Expansion of an Oxaphosphirane Complex with an Electron-Withdrawing C-Substituent

A study on the acid-induced ring-expansion reaction of the first oxaphosphirane complexes bearing an electron-withdrawing C-substituent is described. The stereoselectively obtained 1,3,4-dioxaphospholane complexes 4a–c, representing the first examples of such fluorinated ligands, were unambiguously characterized by multinuclear NMR, elemental analysis, mass spectrometry, and single-crystal X-ray diffraction studies.

Trimethylsilyl imide complexes of tantalum: Can the silyl group be eliminated?

We report the synthesis and structure of a series of tantalum(V) complexes having the trimethylsilylimide moiety and using as ancillary support the pincer ligand PNP (PNP−=N[2-PiPr2-4-methylphenyl]2). Via transmetallation of Li(PNP) with Cl3(py)2TaN{SiMe3} (py=pyridine), the precursor complex (PNP)TaN{SiMe3}Cl2 (1) could be prepared in 94% isolated yield. Attempts to promote FSiMe3 elimination when 1 was treated with FSnMe3 resulted in mixtures from which the salt-like product [{(PNP)TaN{SiMe3}}2(μ2-F)3][Me3ClSn(μ2-X)SnClMe3] (2) (X−=F or Cl) was structurally identified. However, conducting the reaction with NaOAr (Ar=2,6-iPr2C6H3) resulted in clean formation to (PNP)TaN{SiMe3}(OAr)Cl (3) in 79% isolated yield, and when 3 was mixed with FSnMe3, the fluoride-imide complex (PNP)TaN{SiMe3}(OAr)F (4) and ClSnMe3 were formed cleanly. Attempts to promote FSiMe3 elimination in 4 thermally and photochemically did not yield the desired nitride (PNP)TaN(OAr). Complexes 1–4 were characterized by single-crystal X-ray diffraction studies and in the case of complexes 1, 3 and 4 a variety of multinuclear NMR studies are presented and discussed.

Tandem ethylene dimerization and Friedel-Crafts alkylation of toluene catalyzed by homo- and heterogeneous nickel(II) and palladium(II) pre-catalysts

Palladium(II) and nickel(II) complexes (1–4) of the Schiff base ligands, N-(2-pyridinylmethylene)-3-(triethoxysilyl)-1-propanamine (L1) and N-(1-(pyridin-2-yl)ethylidene)-3-(triethoxysilyl)-1-propanamine (L2), have been synthesized and characterized by FT-IR and elemental analysis. The palladium complexes were also characterized by multinuclear NMR studies and the molecular structure of one of palladium complex, 1, was authenticated by X-ray crystallography. Complex 1 and the two nickel complexes, 3 and 4, were evaluated as pre-catalysts for ethylene oligomerization reactions using EtAlCl2 as co-catalyst. On activation with EtAlCl2, the complexes form active catalysts which dimerize ethylene to mainly butenes and subsequently, and these butenes undergo Friedel-Crafts alkylation of toluene (the solvent used for the ethylene reactions); leading to the formation of regioisomers of mono-, di- and tri-butyltoluenes. The nickel complexes, 3 and 4, were also immobilized on silica support to give the nickel pre-catalysts m1 and m2, which are also active for ethylene dimerization and subsequent Friedel-Crafts alkylation of toluene.

A Highly Chemoselective Cobalt Catalyst for the Hydrosilylation of Alkenes using Tertiary Silanes and Hydrosiloxanes

The hydrosilylation of alkene substrates bearing additional functionalities is difficult to achieve using earth-abundant catalysts and has not been extensively realized with both earth-abundant transition metals and tertiary silanes or hydrosiloxanes. Reported herein is a well-defined bis(carbene) cobalt(I)-dinitrogen complex for the efficient, catalytic anti-Markovnikov hydrosilylation of terminal alkenes, featuring a broad substrate scope. Alkenes containing hydroxyl, amino, ester, epoxide, ketone, formyl, and nitrile groups are selectively hydrosilylated in this reaction sequence. Multinuclear NMR studies of reactive intermediates gave insights into the mechanism.

A Ni0(η2-(Si–H))(η2-H2) Complex That Mediates Facile H Atom Exchange between Two σ-Ligands

σ-adduct complexes of low-valent, late first-row metal complexes are highly unusual, and this is particularly true of d10 systems. We have discovered a nickel/phosphine/silyl system that undergoes reaction with H2 in solution to generate a species best described as Ni0(η2-(Si–H))(η2-H2) on the basis of multinuclear NMR studies. Theoretical calculations suggest that the Ni center facilitates H atom exchange between the η2-(Si–H) and η2-H2 ligands via interconversion with a higher valent NiII isomer. This exchange is exploited in the selective, catalytic deuteration of exogenous silanes.

Equilibrium and Multinuclear NMR Spectroscopic Studies of Di- and Trimethyltin(IV) Moieties with Hydroxycarboxylic Acids in Aqueous Medium

The complex formation of [Me2Sn]2+/[Me3Sn]+ with glucuronic [(HL-1)], mandelic [(HL-2)] and gallic [(HL-3)] acids has been studied potentiometrically in aqueous solution (I = 1.0 mol·dm−3 KNO3, 298 ± 0.1 K) and the speciation of various complex species has been evaluated as a function of pH. The results show that these hydroxycarboxylic acid ligands (HL) coordinate via the deprotonated oxygen atom of the carboxylate group resulting in the formation of mixed hydroxo species [Me2Sn(L)(OH)] (12.6–46.2 % in 1:1, 18.3–64.0 % in 1:2) along with [Me2Sn(L)]+ (9.2–18.0 % in 1:1, 14.8–27.8 % in 1:2) in Me2Sn(IV)–(HL) systems and single 1:1 species [Me3Sn(L)] (7.1–12.2 % in 1:1, 13.2–21.7 % in 1:2) in Me3Sn(IV)–(HL) systems at acidic pHs. At physiological pH ~7.0, the major species is [Me2Sn(OH)2] (96.0–97.5 % in 1:1, 92.4–97.2 % in 1:2) with minor amount of [Me2Sn(L)(OH)] (0.4–2.5 % in 1:1, 1.0–5.8 % in 1:2) in Me2Sn(IV)–(HL) systems. Similarly, in Me3Sn(IV)–(HL) systems the major species formed is [Me3Sn(OH)] (86.6–91.5 % in 1:1, 84.7–89.3 % in 1:2) with a very small amount of [Me3Sn(L)] (1.0–1.4 % in 1:1, 1.7–3.0 % in 1:2). At pH >8.0, only hydroxo species are formed, viz. [Me2Sn(OH)2], [Me2Sn(OH)3]− and [Me3Sn(OH)]. In all of the systems, no polymeric species were observed in the studied pH range. Multinuclear (1H, 13C and 119Sn) NMR studies, carried out at different pHs, confirmed the species formation and led us to propose their possible geometries in aqueous solution.

Studying metal ion binding properties of a three-way junction RNA by heteronuclear NMR.

Self-splicing group II introns are highly structured RNA molecules, containing a characteristic secondary and catalytically active tertiary structure, which is formed only in the presence of Mg(II). Mg(II) initiates the first folding step governed by the κζ element within domain 1 (D1κζ). We recently solved the NMR structure of D1κζ derived from the mitochondrial group II intron ribozyme Sc.ai5γ and demonstrated that Mg(II) is essential for its stabilization. Here, we performed a detailed multinuclear NMR study of metal ion interactions with D1κζ, using Cd(II) and cobalt(III)hexammine to probe inner- and outer-sphere coordination of Mg(II) and thus to better characterize its binding sites. Accordingly, we mapped (1)H, (15)N, (13)C, and (31)P spectral changes upon addition of different amounts of the metal ions. Our NMR data reveal a Cd(II)-assisted macrochelate formation at the 5'-end triphosphate, a preferential Cd(II) binding to guanines in a helical context, an electrostatic interaction in the ζ tetraloop receptor and various metal ion interactions in the GAAA tetraloop and κ element. These results together with our recently published data on Mg(II) interaction provide a much better understanding of Mg(II) binding to D1κζ, and reveal how intricate and complex metal ion interactions can be.

Diferrocenophosphaborin: A Planar-Chiral, Redox-Active and Anion-Responsive Ambiphilic Ligand.

A new class of Janus-like ambiphilic ligands is introduced. The rigid diferrocene backbone in heterocycles 4-SnP and 4-BP creates an unprecedented chiral environment as demonstrated by multinuclear NMR and single-crystal X-ray studies. In addition, the ligands are redox-responsive and the Lewis acidic borane moiety in 4-BP can be exploited to further tune the properties: a clear decrease in the CO stretching frequency of a Vaska-type Rh(I) complex 5-BP is observed upon addition of fluoride ions. Thus, the Lewis acid and Lewis base sites influence each other and their strength can be modulated by redox chemistry and anion binding.

Rapid one-pot synthesis of cycloheptatriene-phosphonium derivatives

The direct combination reaction of tropylium tetrafluoroborate with a range of mono- and bi-dentate phosphines in chlorinated solvents leads to the formation of a series of cycloheptatriene-phosphonium derivatives in excellent yields. Multi-nuclear NMR and single-crystal X-ray diffraction studies confirm the addition of the tropylium ligand to the phosphorous centre to form cycloheptatriene derivatives.