Mixed Amide Research Articles

Liposomal MRI probes containing encapsulated or amphiphilic Fe(III) coordination complexes.

Liposomes containing high-spin Fe(III) coordination complexes were prepared towards the production of T1 MRI probes with improved relaxivity. The amphiphilic Fe(III) complexes were anchored into the liposome with two alkyl chains to give a coordination sphere containing mixed amide and hydroxypropyl pendant groups. The encapsulated complex contains a macrocyclic ligand with three phosphonate pendants, [Fe(NOTP)]3-, which was chosen for its good aqueous solubility. Four types of MRI probes were prepared including those with intraliposomal Fe(III) complex (LipoA) alone, amphiphilic Fe(III) complex (LipoB), both intraliposomal and amphiphilic complex (LipoC) or micelles formed with amphiphilic complex. Water proton relaxivities r1 and r2 were measured and compared to a small molecule macrocyclic Fe(III) complex containing similar donor groups. Micelles of the amphiphilic Fe(III) complex had proton relaxivity values (r1 = 2.6 mM-1 s-1) that were four times higher than the small hydrophilic analog. Liposomes with amphiphilic Fe(III) complex (LipoB) have a per iron relaxivity of 2.6 mM-1 s-1 at pH 7.2, 34 °C at 1.4 T whereas liposomes containing both amphiphilic and intraliposomal Fe(III) complexes (lipoC) have r1 of 0.58 mM-1 s-1 on a per iron basis consistent with quenching of the interior Fe(III) complex relaxivity. Liposomes containing only encapsulated [Fe(NOTP)]3- have a lowered r1 of 0.65 mM-1 s-1 per iron complex. Studies show that the biodistribution and clearance of the different types liposomal nanoparticles differ greatly. LipoB is a blood pool agent with a long circulation time whereas lipoC is cleared more rapidly through both renal and hepatobiliary pathways. These clearance differences are consistent with lower stability of LipoC compared to LipoB.

Study of Mixed Amide Coordination Compounds of Copper (II) Nicotinate

Complexes of copper (II) nicotinate with acid amides were synthesized to vary the composition and the individual properties of the compounds obtained through coordination of the nicotinate group to acetamide, carbamide, thiocarbamide and nicotinamide (L1, L2). The coordination of the organic ligands, the environment of the central ion and the thermal behaviour of the synthesized compounds were elucidated by vibrational spectroscopy and thermal analysis. The relative intensities and the spatial structures of copper (II) nicotinate and the synthesized complexes showed that the new coordination compounds differ from each other and the original components, as they have unique crystal lattices. X-ray diffraction (XRD) analysis was used to obtain diffraction patterns of free molecules of ligands, copper nicotinate, and synthesized coordination compounds. The thermal behaviour of the synthesized compounds was investigated and the thermolysis products were identified. The stepwise decomposition of the synthesized compounds was found with several endo - and exo effects correspond to the decomposition of the constituent parts of the complexes. Based on the intensity of the electronic spectrum of diffuse reflection and the values of the bands, the six-coordination environment of Cu (II) the synthesized complexes was proven.

Compositional characterization of complex protopeptide libraries via triboelectric nanogenerator Orbitrap mass spectrometry.

Understanding of the molecular processes that led to the first biomolecules on Earth is one of the key aspects of origins-of-life research. Depsipeptides, or polymers with mixed amide and ester backbones, have been proposed as plausible prebiotic precursors for peptide formation. Chemical characterization of depsipeptides in complex prebiotic-like mixtures should benefit from more efficient ion sources and ultrahigh-resolution mass spectrometry (UHR-MS) for elemental composition elucidation. A sliding freestanding (SF) Triboelectric Nanogenerator (TENG) was coupled to glass nanoelectrospray emitters for the analysis of a depsipeptide library created using 11 amino acids and 3 alpha-hydroxy acids subjected to environmentally driven polymerization. The TENG nanoelectrospray ionization (nanoESI) source was coupled to an UHR Orbitrap mass spectrometer operated at 1,000,000 resolution for detecting depsipeptides and oligoesters in such libraries. Tandem mass spectrometry (MS/MS) experiments were performed on an Orbitrap Q-Exactive mass spectrometer. Our previous proteomics-like approach to depsipeptide library characterization showed the enormous complexity of these dynamic combinatorial systems. Here, direct infusion UHR-MS along with de novo sequencing enabled the identification of 524 sequences corresponding to 320 different depsipeptide compositions. Van Krevelen and mass defect diagrams enabled better visualization of the chemical diversity in these synthetic libraries. TENG nanoESI coupled to UHR-MS is a powerful method for depsipeptide library characterization in an origins-of-life context.

Lewis acidic alkaline earth metal complexes with a perfluorinated diphenylamide ligand.

Alkaline earth metal (Ae) chemistry with the anion [N(C6F5)2]- has been explored. Deprotonation of the amine (C6F5)2NH, abbreviated in here as NFH, with 0.5 equivalent of AeN''2 (N'' = N(SiMe3)2) is fast and gave, dependent on the solvent, the complexes AeNF2, AeNF2·(THF)2 and AeNF2·(Et2O)2 (Ae = Mg, Ca, Sr). Using a 1/1 ratio, mixed amide complexes were obtained: NFAeN'' (Ae = Mg, Ca, Sr). Crystal structures of the monomers AeNF2·(THF)2 (Ae = Mg, Ca, Sr) and AeNF2·(Et2O)2 (Ae = Mg, Ca) are presented and compared with those of AeN''2·(THF)2. In addition, crystal structures of the homoleptic dimer (MgNF2)2 and the heteroleptic dimers (NFAeN'')2 (Ae = Mg, Ca, Sr) are discussed. All structures are strongly influenced by very short AeF contacts down to circa 2.11 Å (Mg), 2.50 Å (Ca) and 2.73 Å (Sr). AIM analysis illustrates that, although AeF contacts are short, there is no bond-critical-point along this axis, indicating an essentially electrostatic interaction. The monomeric complexes feature strong C6F5C6F5π-stacking, resulting in unusually acute NF-Ae-NF angles as small as 95°. Heteroleptic (NFAeN'')2 complexes retain their dimeric structure in C6D6 solution and there is no indication of ligand scrambling by the Schlenk equilibrium, suggesting that an electron withdrawing ligand may stabilize heteroleptic complexes. According to DFT calculations, the heteroleptic arrangement is 70 kJ mol-1 more stable than the homoleptic dimers. The Lewis acidity of MgNF2 has been quantified with the Gutmann-Beckett method and by calculation of the Fluoride-Ion-Affinity. The latter calculations show that the Lewis acidity of MgNF2 and CaNF2 is comparable to that of B(C6F5)3. Dimeric (MgNF2)2 fully abstracts Et3PO from Et3PO·B(C6F5)3 and may have potential in Lewis acid catalysis.

Improved overall hydrogen storage properties of a CsH and KH co-doped Mg(NH2)2/2LiH system by forming mixed amides of Li–K and Cs–Mg

Further improved overall hydrogen storage properties of a Mg(NH2)2/2LiH system is achieved by codoping CsH and KH.

Dispersion of single-walled carbon nanotubes in dimethylacetamide and a dimethylacetamide–cholic acid mixture

A way of dispersing single-walled carbon nanotubes in preparing stable suspensions with high concentrations of individual nanotubes in amide solvents is described. The obtained suspensions are studied via Raman spectroscopy. The dependence of the degree of single-walled carbon nanotube (SWNT) dispersion in individual and mixed amide solvents on the type of solvent, the mass of nanotubes, and the concentration of cholic acid is established. A technique for processing spectral data to estimate the diameters and chiralities of individual nanotubes in suspension is described in detail.

Syntheses and Characterization of Tantalum Alkyl Imides and Amide Imides. DFT Studies of Unusual α-SiMe3 Abstraction by an Amide Ligand

Reaction of TaCl2(═NSiMe3)[N(SiMe3)2] (1) with alkylating reagents form the alkyl amide imide complexes TaR2(═NSiMe3)[N(SiMe3)2] (R = Me (2), CH2Ph (3)) and mixed amide imide compounds Ta(NR′2)2(═NSiMe3)[N(SiMe3)2] (R′ = Me (4), Et (5)). The reaction of 2 and 0.5 equiv of O2 leads to preferential oxygen insertion into one Ta–Me bond, yielding the alkoxy-bridged alkyl dimer Ta2(μ-OMe)2Me2(═NSiMe3)2[N(SiMe3)2]2 (6) as cis and trans isomers. Crystallization of the cis-6 and trans-6 mixture gave only crystals of trans-6. When the crystals of trans-6 were dissolved in benzene-d6, conversion of trans-6 to cis-6 occurred until the trans-6 ⇌ cis-6 equilibrium was reached with Keq = 0.79(0.02) at 25.0(0.1) °C. Kinetic studies of the exchange gave the rate constants k = 0.018(0.002) min–1 for the trans-6 → cis-6 conversion and k′ = 0.022(0.002) min–1 for the reverse cis-6 → trans-6 conversion at 25.0(0.1) °C. Complex 6 reacts with additional O2, forming the dialkoxy dimer Ta2(μ-OMe)2(OMe)2(═NSiMe3)2[N(SiMe3)2]2 (7)...

UTILIZAÇÃO DE DIFERENTES DILUENTES NA CRIOPRESERVAÇÃO DE ESPERMATOZOIDES DE GARANHÕES MANGALARGA MARCHADOR

The techniques applied to animal reproduction such as artificial insemination, transfer and in vitro production of embryos, heat synchronization and induction, and gametes cryopreservation have been more utilized in veterinary practice each day. Nevertheless, some techniques have not achieved their full technical capacity within the equine reproduction field, such as semen cryopreservation. The aim of this study was to evaluate the characteristics of post-thawing semen (total motility, strength, plasmatic and acrosomal membrane integrity) of Mangalarga Marchador breed stallions, using three different extenders (Botucrio, FR5 and FR6). Ejaculates from five stallions were collected and the gel-free semen was diluted in a 1:1 dilution in skim milk extender, and centrifuged at 600 g for 10 minutes. After the centrifugation the supernatant was removed and sperm pellet was divided and re-suspended using three different extenders to a concentration of 200 x 10 6 cells/mL. The samples were packed into 0.5 mL straws, placed in a stainless steel support and kept inside the refrigerator (5 o C) for one hour. Subsequently, these straws were kept at a height of 6 cm from liquid nitrogen for 15 minutes in an isotherm box and, after that, plunged into liquid nitrogen (-196 o C) and stored in a liquid nitrogen holding tank. There were no differences in the parameters evaluated when extenders using mixed amides and glycerol (Botucrio and FR6) were used (P > 0.05). All parameters evaluated were lower for the extender containing only glycerol (P<0.05). The use of cryoprotectants (methylformamide and dimethylformamide) in association with glycerol concentrations around 1 to 2% is an alternative for semen cryopreservation of Mangalarga Marchador breed stallions. Keywords : amides; cryoprotectant; equine; frozen semen; glycerol.

Synthesis and evaluation of ligands with mixed amide and phosphonate, phosphinoxide, and phosphonothioate sites for An(iii)/Ln(iii) extraction

Various organophosphorus ligands with a combination of different donor sites were synthesized and evaluated by solvent extraction studies for the complexation of Am(III)/Eu(III). Among the ligands with a glycolamide backbone, those with mixed amide and PO donor sites and a central oxygen or nitrogen atom showed a reasonable extraction of Am(III) and Eu(III). Ligands with a central oxygen atom exhibited selectivity towards Eu(III), and those with a central nitrogen atom towards Am(III). Ligands with PS donor sites and a glycolamide backbone did not show any reasonable extraction. Amongst the ligands with a malonamide backbone, high extraction efficiency was observed for the ligand with electron-rich substituents on phosphorus, however, with almost no discrimination between Am(III) and Eu(III). The extraction efficiency of different ligands towards Eu(III) was confirmed by microcalorimetry.

Monocyanomethylated thiacalix[4]arenes: synthesis and lower rim modification

The selective monocyanomethylation of p-R-thiacalix[4]arenes (R = H, tert-Bu) with chloroacetonitrile in the presence of Na2CO3 in DMF is described. Monocyanomethylated p-tertbutylthiacalix[4]arene has been synthetically exploited in the Ritter reaction with 1-adamantanol for the transformation to the corresponding amide. A thiacalix[4]arene having mixed amide and ester functionalities at the lower rim was synthesized by alkylation of 25-N-(1adamantyl)carbamoylmethoxy-p-tert-butylthiacalix[4]arene with ethyl bromoacetate.

CMPO-calix[4]arenes and the influence of structural modifications on the Eu(III), Am(III), Cm(III) separation

The syntheses of new calix[4]arenes featuring CMPO groups on the wide rim are reported and the extraction of Am(III) and Eu(III) from concentrated HNO3 aqueous phases are discussed with reference to the properties of the symmetric tetra-CMPO derivative 1 . All extraction studies were conducted in the same experimental conditions which allows to directly compare the dependence of the distribution coefficients of various calixarenes on the acid concentration (0.1 M &lt; [HNO3] &lt; 5 M). Calix[4]arene 1 becomes a very poor extractant if the length of the aliphatic chain between the amide and phosphine oxide groups of CMPO is increased, if the bridging methylene groups are replaced by sulfur atoms or if the macrocyclic cavity size is increased. By contrast, mixed amide — CMPO calix[4]arenes are nearly as effective than 1 . Moreover, Am(III)/Cm(III) separation coefficients between 1.5 and 3 have been obtained with unsymmetrical calix[4]arenes of type 1 with different aliphatic chains grafted on the narrow rim. Guidelines to anticipate the extraction ability of calix[4]arenes remain elusive because of the intricate solution behavior of these compounds.

Structuring in mixed solvents: Study by polarized light scattering

The structure of mixed amide solvents used for the preparation of polyimide Langmuir-Blodgett films and the structural organization of water, on which nanofilms are formed, have been studied by polarized light scattering. Fluctuation supramolecular structures are found to exist in water and in its mixtures with amide solvents, and the dimensions of the structures are comparable with the light wavelength. When a mixture contains more than 20 vol % water, associates show microanisotropic properties. In snowmelt water, the dimensions of associates are larger than those in distilled water. In the DMAA-water mixture, the dimensions of supramolecular structures are virtually independent of composition.

Mixed amide–malonate compound of hafnium as a novel monomeric precursor for MOCVD of HfO2thin films

The concept of introducing malonates as chelating ligands in combination with metal amides has yielded a new class of compounds which enable growth of HfO2 thin films at low deposition temperatures by liquid injection metalorganic chemical vapour deposition.

Alkali Metal Complexation. Binding Properties of cone and partial-cone Calix[4]arenes Bearing a Mixed (O2, O2') Donor Set (O = Phosphine Oxide; O' = Amide or Ester)

The stability constants of alkali metal complexes obtained from the followingO-substituted calix[4]arenes were determined by UV/Vis spectroscopy inmethanol at 20°C: 5,11,17,23-tetra-tert-butyl-25,27-bis(diethylcarbamoylmethoxy)-26,28-bis(diphenylphosphinoylmethoxy)calix[4]arene(cone-1), 25,27-syn-26,28-anti-5,11,17,23-tetra-tert-butyl-25,27-bis(diethylcarbamoylmethoxy)-26,28-bis(diphenylphosphinoylmethoxy)calix[4]arene (paco-1),5,11,17,23-tetra-tert-butyl-25,27-diethoxycarbonylmethoxy-26,28-bis(diphenylphosphinoylmethoxy)calix[4]arene(cone-2) and25,27-syn-26,28-anti-5,11,17,23-tetra-tert-butyl-25,27-diethoxycarbonylmethoxy-26,28-bis(diphenylphosphinoylmethoxy)calix[4]arene(paco-2). All ligands form 1:1 complexes with alkali metal cations. The amide-containing calixarenes were found to be more efficient for alkali metalcomplexation than those bearing ester substituents. While sodium ions are selectivelycomplexed by the two mixed amide-(phosphine oxide) calixarenes, the twoester-containing isomers cone-2 and paco-2 turned out to be selective towards potassium and rubidium ions, respectively. With allfour ligands the lowest stability constants were found for the lithium andcesium ions.

Dicaffeoyltartaric acid analogues inhibit human immunodeficiency virus type 1 (HIV-1) integrase and HIV-1 replication at nontoxic concentrations.

The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues of L-chicoric acid, a potent inhibitor of HIV integrase, were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less than 10 microM were identified. Six demonstrated greater than 10-fold selectivity for HIV replication over cellular toxicity. Ten analogues inhibited HIV replication at nontoxic concentrations. Alteration of the linkages between the two bis-catechol rings, including the use of amides, mixed amide esters, cholate, and alkyl bridges, was explored. Amides were as active as esters but were more toxic in tissue culture. Alkyl and cholate bridges were significantly less potent against HIV-1 integrase in vitro and were inactive against HIV-1 replication. Two amino acid derivates and one digalloylderivative of L-chicoric acid (L-CA) showed improved selectivity over L-CA against integration in cell culture. These data suggest that in addition to the bis-catechols and free carboxylic acid groups reported previously, polar linkages are important constituents for optimal activity against HIV-1 integrase and that new derivatives can be developed with increased specificity for integration over HIV entry in vivo.

Solution-Phase Synthesis of Mixed Amide Libraries by Simultaneous Addition of Functionalities (SPSAF) to a Diketopiperazine Tetracarboxylic Acid Scaffold Monitored by GC Analysis of Isobutyl Alcohol

A symmetric diketopiperazine scaffold 2 has been prepared in a very simple two-step procedure from L-aspartic acid dimethyl ester. This product (a tetracarboxylic acid equally protected at the two symmetric positions) has been employed as a template for the synthesis of mixed amide libraries in the solution phase using the SPSAF (simultaneous addition of functionalities) strategy. By judicious choice of the amines employed, it is possible to prepare parallel libraries containing hundreds of products using just a small number of different amines. We have also developed a simple method for monitoring the required conversion of the acid into amides based on an assay of the amount of iBuOH (determined by GC) formed during the coupling mediated by isobutyl chloroformate. We have observed that a conversion higher than 90% (iBuOH by GC) guarantees correct formation of the desired amides. This indirect method for assessing the conversion in a combinatorial reaction employing mixed reactants (SPSAF) can conveniently be used for the routine determination of libraries prepared in the solution phase. In a broader perspective, the present results contribute as a further step in the development of new and simple systems for monitoring the progress and evolution of combinatorial reactions

Synthesis of the mixed lithium–magnesium, mixed amide (R,R/S,S)-[{LiMg(TMP)[CH2Si(Me)2N(SiMe3)]}2]: a conformationally-locked structure of five fused rings inducing two stereogenic nitrogen centres

Reaction of the magnesium amide Mg(TMP)2 with the lithium amide LiHMDS is accompanied by an unexpected, sterically-promoted hydrogen transfer/amine elimination process, to yield the novel title compound which is the first such heterometallic composition to contain a heteroleptic amide ligand set.

Synthesis and X-ray crystal structure of trans-dichloro(1-cyano-2,2-dimethylpropane)(1-imino-1-hydroxy-2,2-dimethylpropane)platinum(II)

Nitrile complexes of platinum easily hydrolyze to amidate, amide, and mixed amide–nitrile complexes. The amide ligands generally adopt the enol tautomeric form and coordinate to platinum through nitrogen. A mixed amide–nitrile complex, trans-[PtCl 2{HN=C(OH)C(CH 3) 3}{N≡CC(CH 3) 3}] ( trans- 3), has shown to be the complex previously formulated as a platinum(IV) dichlorobisamidate derivative having the two amidate ligands in different tautomeric forms. The structure of trans- 3 has been solved by single-crystal diffraction. The complex crystallizes in the Pbcn space group. The crystal structure has strong similarities with that previously reported by some of us for trans-[PtCl 2{HN=C(OH)C(CH 3) 3} 2] [R. Cini, F.P. Fanizzi, F.P. Intini, C. Pacifico, G. Natile, Inorg. Chim. Acta 264 (1997) 279]. Triplets of complex molecules are stabilized by intra-molecular hydrogen bonds involving N, Cl and O atoms.

Ortho-substituted aryl diamido complexes of zirconium: observation of rotameric isomers

Zirconium complexes bearing a series of ortho-substituted aryl diamido ligands [2,6-(RNCH 2) 2NC 5H 3] 2− (R = 2-PhC 6H 4 (BPhP); 2- i PrC 6H 4 (BMPP); 2- i BuC 6H 4 (BMBP), 2- i Pr-6-MeC 6H 3 (MPPP)) have been synthesized. The mixed amide complexes [2,6-(RNCH 2) 2NH 5H 3]Zr(NMe 2) 2 are prepared in high yield from 2,6-(RHNCH 2) 2NC 5H 3 and Zr(NMe 2) 4. The mixed amides react with excess ClSiMe 3 to afford the dichlorides [2,6-(RNCH 2) 2NC 5H 3]ZrCl 2 in nearly quantitative yield. Dimethyl complexes are prepared from [2,6-(RNCH 2) 2NC 5H 3]ZrCl 2 and 2 equiv. of MeMgCl. NMR spectroscopy has been used to identify rotameric isomers derived from restricted rotation about the NC ipso bond of the ligand. The aryl groups in (BPhP)ZrX 2 complexes freely rotate at all temperatures (−80 to +80°C) while (BMPP)ZrX 2 (X  NMe 2, Cl, Me) derivatives adopt meso and rac rotamers at low temperatures. In contrast, (BMBP)ZrX 2 and (MPPP)ZrX 2 (X  NMe 2, Cl, Me) compounds are locked at all temperatures. (BMBP)ZrCl 2 is isolated as a single isomer, likely the meso rotamer, while (MPPP)ZrCl 2 is a near statistical mixture of meso and rac isomers.

Synthesis and crystal structure of [U(η-C 5Me 5) 2(OC 4H 8) 2][BPh 4], the first cationic cyclopentadienyl compound of uranium(III)

The mixed amide complexes [U(NEt 2) 2(N{SiMe 3} 2) 2] and [U(η-C 8H 8)(NEt 2)(N{SiMe 3} 2)] reacted in tetrahydrofuran (THF) with NEt 3HBPh 4 to give the cations [U(NEt 2)(N{SiMe 3} 2) 2(THF) x ] + and [U(η-C 8H 8)(N{SiMe 3} 2)(THF) x ] +. The bis(trimethylsilyl) amide complex [U(η-C 5Me 5) 2(N{SiMe 3} 2)] was inert towards NEt 3HBPh 4 but its treatment with NH 4BPh 4 afforded the cationic uranium(III) compound [U(η-C 5Me 5) 2(THF) 2][BPh 4], the crystal structure of which has been determined.