Cobalt(II) alkyl complexes of aliphatic PNP pincer ligands have been synthesized and characterized. The cationic cobalt(II) alkyl complex (PNHPCy)Co(CH2SiMe3)BArF 4 (4) (PNHPCy = ...bis(2-dicyclohexylphosphino)ethylamine) is an active precatalyst for the hydrogenation of olefins and ketones and the acceptorless dehydrogenation of alcohols. To elucidate the possible involvement of the N–H group on the pincer ligand in the catalysis via a metal–ligand cooperative interaction, the reactivities of 4 and (PNMePCy)Co(CH2SiMe3)BArF 4 (7) were compared. Complex 7 was found to be an active precatalyst for the hydrogenation of olefins. In contrast, no catalytic activity was observed using 7 as a precatalyst for the hydrogenation of acetophenone under mild conditions. For the acceptorless dehydrogenation of 1-phenylethanol, complex 7 displayed similar activity to complex 4, affording acetophenone in high yield. When the acceptorless dehydrogenation of 1-phenylethanol with precatalyst 4 was monitored by NMR spectroscopy, the formation of the cobalt(III) acetylphenyl hydride complex (PNHPCy)CoIII(κ2-O,C-C6H4C(O)CH3)(H)BArF 4 (13) was detected. Isolated complex 13 was found to be an effective catalyst for the acceptorless dehydrogenation of alcohols, implicating 13 as a catalyst resting state during the alcohol dehydrogenation reaction. Complex 13 catalyzed the hydrogenation of styrene but showed no catalytic activity for the room temperature hydrogenation of acetophenone. These results support the involvement of metal–ligand cooperativity in the room temperature hydrogenation of ketones but not the hydrogenation of olefins or the acceptorless dehydrogenation of alcohols. Mechanisms consistent with these observations are presented for the cobalt-catalyzed hydrogenation of olefins and ketones and the acceptorless dehydrogenation of alcohols.
The present work details a material sparing approach that combines material profiling with Instron uniaxial die-punch tester and use of a roller compaction mathematical model to guide both ...formulation and process development of a roller-compacted drug product. True density, compression profiling, and frictional properties of the pre-blend powders are used as inputs for the predictive roller compaction model, while flow properties, particle size distribution, and assay uniformity of roller compaction granules are used to select formulation composition and ribbon solid fraction. Using less than 10 g of a model drug compound for material profiling, roller compacted blend in capsule formulations with appropriate excipient ratios were developed at both 1.4% and 14.4% drug loadings. Subsequently, scale-up batches were successfully manufactured based on the roller compaction process parameters obtained from predictive modeling. The measured solid fractions of roller compaction ribbon samples from the scale-up batches were in good agreement with the target solid fraction of the modeling. This approach demonstrated considerable advantages through savings in both materials and number of batches in the development of a roller-compacted drug product, which is of particular value at early development stages when drug substance is often limited and timelines are aggressive.
Three new binuclear lanthanide complexes of general formula Ln2(L)6(H2O)4 (Ln = Tb (1), Eu (2), and Gd (3)) supported by the novel aromatic carboxylate ligand 4-(dibenzylamino)benzoic acid (HL) have ...been synthesized. Complexes 1 and 2 were structurally characterized by single-crystal X-ray diffraction. Both 1 and 2 crystallize in the triclinic space group P 1̅, and their molecular structures consist of homodinuclear species that are bridged by two oxygen atoms from two carboxylate ligands via different coordination modes. The discrete bridged dimer of 1 is centrosymmetric and features 8-coordinate terbium atoms, each of which adopts a distorted square-antiprismatic geometry. Both coordination spheres comprise two η2-chelating benzoates, two μ-η1:η1 -carboxylate interactions from the bridging benzoates, and two water molecules. By contrast, in complex 2, the Eu3+ ion coordination environment is best described as a distorted tricapped-trigonal prism, each europium ion being coordinated to three η2-chelating benzoate ligands and two water molecules. One of the η2-carboxylate ligands is involved in a further interaction with an adjacent metal, thus rendering the overall binding mode bridging tridentate, μ-η2:η1. Scrutiny of the packing diagrams for 1 and 2 revealed the existence of a one-dimensional molecular array that is held together by intermolecular hydrogen-bonding interactions. The Tb3+ complex 1 exhibits high green luminescence efficiency in the solid state with a quantum yield of 82%. On the other hand, poor luminescence efficiency has been noted for the Eu3+−4-(dibenzylamino)benzoate complex.
Three new 4-benzyloxy benzoic acid derivatives 4-benzyloxy benzoic acid = HL1; 3-methoxy-4-benzyloxy benzoic acid = HL2; 3-nitro-4-benzyloxy benzoic acid = HL3 have been employed as ligands for the ...support of six lanthanide coordination compounds Tb(3+) = 1-3; Eu(3+) = 4-6 with the aim of testing the influence of electron releasing (-OMe) or electron withdrawing (-NO(2)) substituents on the photophysical properties. The new complexes have been characterized by a variety of spectroscopic techniques and two of the Tb(3+) complexes 1 and 2 have been structurally authenticated by single-crystal X-ray diffraction. Compounds 1 and 2 crystallize in the monoclinic space group P21/n. The molecular structure of 1 consists of homodinuclear species that are bridged by two oxygen atoms from two benzoate ligands corrected.In the case of 1, the carboxylate ligands coordinate to the central Tb(3+) ion in bidentate chelating and bidentate bridging modes. By contrast, the X-ray structure of 2 reveals that each Tb3+ ion is connected to two neighboring ions by four methoxy substituted benzoates via the carboxylate groups in bridging mode to form an infinite one-dimensional coordination polymer corrected. Examination of the packing diagrams for 1 and 2 revealed the presence of a one-dimensional molecular array that is held together by intermolecular hydrogen-bonding interactions. The incorporation of an electron-releasing substituent on position 3 of 4-benzyloxy benzoic acid increases the electron density of the ligand and consequently improves the photoluminescence of the Tb(3+) complexes. On the other hand, the presence of an electron-withdrawing group at this position dramatically decreases the overall sensitization efficiency of the Tb(3+)-centered luminescence due to dissipation of the excitation energy by means of a pi*-n transition of the NO(2) substituent along with the participation of the ILCT bands. The weaker photoluminescence of the Eu(3+) complexes is attributable to the poor match of the triplet energy levels of the 4-benzyloxy benzoic acid derivatives with that of the emitting level of the central metal ion.
Three new lanthanide heterocyclic β-diketonate complexes having the general formula Ln(PBI)3(DPEPO) HPBI = 3-phenyl-4-benzoyl-5-isoxazolone, DPEPO = bis(2-(diphenylphosphino)phenyl) ether oxide and ...Ln3+ = Eu3+ (1), Tb3+ (2), and Gd3+ (3) have been synthesized. Compounds 1 and 2 were characterized by single-crystal X-ray diffraction. The single-crystal X-ray diffraction analyses of 1 and 2 revealed that these complexes are mononuclear, and that the central Ln3+ ion is coordinated by six oxygen atoms furnished by three bidentate β-diketonate ligands and two oxygen atoms from the bidentate DPEPO ligand. The overall molecular geometry is distorted square prismatic. Examination of the packing diagrams for 1 and 2 revealed the presence of interesting molecular ladder structures held together by π···π and intermolecular hydrogen-bonding interactions. The effect of the chelating ancillary phosphine oxide ligand DPEPO on the sensitized luminescence of Eu3+ and Tb3+ luminescence in these heterocyclic β-diketonate complexes has been investigated. The ancillary ligand increases considerably the luminescence efficiency of Eu(PBI)3(DPEPO) (overall quantum yield 2−30%; 5D0 lifetime 250−1056 μs) compared to Eu(PBI)3(C2H5OH)(H2O), through the formation of intraligand states, while it is detrimental to Tb3+ luminescence in Tb(PBI)3(DPEPO) (overall quantum yield 11 to 0.5%; 5D4 lifetime 400 to 168 μs).
The bis(imino)acenaphthene-supported N-heterocyclic carbene IPr(BIAN) has been prepared by deprotonation of the precursor imidazolium chloride. Treatment of IPr(BIAN) imidazolium chloride with Ag(2)O ...afforded the silver complex IPr(BIAN)AgCl which can be converted into the corresponding gold complex IPr(BIAN)AuCl by reaction with (tht)AuCl (tht = tetrahydrothiophene). The iridium complex IPr(BIAN)Ir(COD)Cl was prepared by reaction of the imidazolium chloride with KO(t)Bu and Ir(COD)Cl(2) and subsequently converted to the carbonyl complex IPr(BIAN)Ir(CO)(2)Cl by exposure to an atmosphere of CO. All new compounds were characterized by single-crystal X-ray diffraction, multinuclear NMR, MS and HRMS data.
A hot tip: Bifunctional tetrakis(imino)pyracene (tip) ligands undergo one‐electron reduction at both diimine functionalities when treated with potassium metal, germanium dichloride, or ...decamethyleuropocene (see scheme, Cp*=C5Me5). The transferred electrons pair up in an orbital that is delocalized over both diazabutadiene moieties and the naphthalene bridge.
We report the crystallization of a metastable small-molecule solvate and the effect of the isolation method on the physical and material properties of the resulting anhydrous material. The anhydrous ...crystalline products obtained from two different isolation routes using either a temperature-driven form change or a solvent-wash-mediated form change were analyzed by a suite of material-sparing characterization methods probing both physical form and material properties such as particle size distribution and powder flow behavior. The temperature-driven desolvation method was found to be time-consuming and undesirable. A relatively rapid desolvation approach was obtained using an ethyl acetate wash-mediated process. However, this method leads to powder with a broader particle size distribution, poorer flowability, higher interparticulate friction, and lower bulk density compared with the powder obtained by the temperature-driven desolvation process. The direct impact of the method of isolation on the material properties of the drug substance highlights the importance of not only understanding the crystallization process and form landscape but also the ability to implement systematic characterization to identify key powder properties of drug candidates early in the drug development process.
The first two examples of a new class of bifunctional BIAN-type ligand have been prepared, and the reactions of one such ligand with CuBr(2) and BCl(3) have been explored.
A new aromatic carboxylate ligand, 4-4-(9H-carbazol-9-yl)butoxybenzoic acid (HL), has been synthesized by the replacement of the hydroxyl hydrogen of 4-hydroxy benzoic acid with a ...9-butyl-9H-carbazole moiety. The anion derived from HL has been used for the support of a series of lanthanide coordination compounds Ln = Eu (1), Gd (2) and Tb (3). The new lanthanide complexes have been characterized by a variety of spectroscopic techniques. Complex 3 was structurally authenticated by single-crystal X-ray diffraction and found to exist as a solvent-free 1D coordination polymer with the formula Tb(L)(3)(n). The structural data reveal that the terbium atoms in compound 3 reside in an octahedral ligand environment that is somewhat unusual for a lanthanide. It is interesting to note that each carboxylate group exhibits only a bridging-bidentate mode, with a complete lack of more complex connectivities that are commonly observed for extended lanthanide-containing solid-state structures. Examination of the packing diagram for revealed the existence of two-dimensional molecular arrays held together by means of CH-π interactions. Aromatic carboxylates of the lanthanides are known to exhibit highly efficient luminescence, thus offering the promise of applicability as optical devices. However, due to difficulties that arise on account of their polymeric nature, their practical application is somewhat limited. Accordingly, synthetic routes to discrete molecular species are highly desirable. For this purpose, a series of ternary lanthanide complexes was designed, synthesized and characterized, namely Eu(L)(3)(phen) (4), Eu(L)(3)(tmphen) (5), Tb(L)(3)(phen) (6) and Tb(L)(3)(tmphen) (7) (phen = 1,10-phenanthroline and tmphen = 3,4,7,8-tetramethyl-1,10-phenanthroline). The photophysical properties of the foregoing complexes in the solid state at room temperature have been investigated. The quantum yields of the ternary complexes 4 (9.65%), 5 (21.00%), 6 (14.07%) and 7 (32.42%), were found to be significantly enhanced in the presence of bidentate nitrogen donors when compared with those of the corresponding binary compounds 1 (0.11%) and 3 (1.45%). Presumably this is due to effective energy transfer from the ancillary ligands.
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