Thin-layer chromatographic enantiomeric resolution via ligand exchange

A thin-layer chromatographic technique for the separation of proteinogenic and non-proteinogenic amino acids, dipeptides and alpha-hydroxy acids is described. Other examples are given from the field of alpha-methyl, N-alkyl and halogenated amino acids. The separation of the enantiomers is achieved, without derivatization, by means of ligand exchange on a reversed-phase silica gel as stationary phase, which is covered with a chiral selector (proline derivative). The resolution is so good that the respective enantiomers can be determined at trace levels (greater than or equal to 0.25%). The proposed method is simple, inexpensive and needs no sophisticated instruments.     

Reductive deamination of aryl- and heteroaryl-amines via pyridinium fluorides

The corresponding “pseudobase” Δ² -1,5-diketones (8) and (14) afford dihydrochromenylium (9b) and tetrahydro-xanthylium monofluorides (15). These convert aryl- and heteroarylamines into dihydroquinolinium (10) and tetrahydro-acridinium (16) monofluorides which at 130–250° give the deaminated arenes and heteroarenes (average overall yield 60%).     

Synthesis of cationic quantum dots via a two-step ligand exchange process

A new class of quaternary ammonium derivatives has been used to synthesize cationic CdSe/ZnS quantum dots with exceptional stability in water as well as in biological media.     

Highly sensitive and selective cyanide detection via Cu2+ complex ligand exchange

A new type of fluorescent probe (1) with two triazole groups that are conjugated with a carbazole moiety was synthesized by a Cu(I)-catalyzed alkyne-azide click reaction for the selective and sensitive detection of cyanide via fluorescence enhancement by ligand exchange and metal ion removal.     

Ligand customization and DNA functionalization of gold nanorods via round-trip phase transfer ligand exchange

Customizable ligand exchange of gold nanorods (NRs) is described. NRs are synthesized with the cationic surfactant cetyltrimethylammonium bromide (CTAB) which is exchanged with thiolated ligands that enable suspension in buffer. Exchange is achieved by a two phase extraction. First, CTAB is removed from the NR-CTAB by extracting the NRs into an organic phase via the ligand dodecanethiol (DDT). The NR-DDT are then extracted into an aqueous phase by mercaptocarboxylic acids (MCA), HS-(CH 2)n -COOH (n = 5, 10, and 15). Ligands can be further customized to thiolated poly(ethylene glycol), PEG MW (MW = 356, 5000, and 1000). Ligand-exchanged NRs (NR-MCA and NR-PEG(MW)) are stable in buffer, do not aggregate, and do not change size upon ligand exchange. They can be run in agarose gel electrophoresis with narrow bands, indicating uniform charge distribution and enabling quantitative analysis. DNA functionalization of NR-MCA is straightforward and quantifiable, with minimal nonspecific adsorption.     

Thiol-functionalized, 1.5-nm gold nanoparticles through ligand exchange reactions: scope and mechanism of ligand exchange

Ligand exchange reactions of 1.5-nm triphenylphosphine-stabilized nanoparticles with omega-functionalized thiols provides a versatile approach to functionalized, 1.5-nm gold nanoparticles from a single precursor. We describe the broad scope of this method and the first mechanistic investigation of thiol-for-phosphine ligand exchanges. The method is convenient and practical and tolerates a surprisingly wide variety of technologically important functional groups while producing very stable nanoparticles that essentially preserve the small core size and size dispersity of the precursor particle. The mechanistic studies reveal a novel three-stage mechanism that can be used to control the extent of ligand exchange. During the first stage of the exchange, AuCl(PPh3) is liberated, followed by replacement of the remaining phosphine ligands as PPh3 (assisted by gold complexes in solution). The final stage involves completion and reorganization of the thiol-based ligand shell.     

Separation of amines by ligand exchange: Part IV ligand exchange with chelating resins and cellulosic exchangers

Chelating, sulfonic and cellulosic exchangers were compared in ligand exchange chromatography. Chelating resins retain metal ions the best, but have a low ligand binding capacity. Cellulosic exchangers show excessive metal leakage. Sulfonated polystyrene resins loaded with nickel ions give best results in most cases. Data are presented on ligand exchange chromatography of simple aliphatic amines, hydrazine and substituted hydrazines, purine and pyrimidine bases.     

Synthesis of aryl- and heteroaryl-substituted 3-benzyloxyisothiazoles via Suzuki and Negishi cross-coupling reactions

Introduction of aryl and heteroaryl substituents into the 5-position of 3-benzyloxyisothiazole (1) using palladium-catalyzed Suzuki and Negishi cross-coupling reactions was investigated. Attempts to generate synthetically viable nucleophilic species from 1 for Suzuki- or Negishi-type cross-couplings were unsuccessful. However, using 3-benzyloxy-5-iodoisothiazole 2 as an intermediate, a range of aromatic and heteroaromatic substituents were successfully introduced under Suzuki or Negishi cross-coupling conditions in good to excellent yields.     

Structural and magnetic studies of two-dimensional solvent-free manganeseII complexes prepared via ligand exchange reaction under solvothermal conditions

Systematic investigation of the ligand exchange reactions between manganese(II) acetate and benzoic acid under solvothermal conditions led to the isolation of crystalline complexes {Mn5(OC(O)CH3)6(OC(O)C6H5)4}(infinity) ( 1) and {Mn5(OC(O)CH3)4(OC(O)C6H5)6}}(infinity) ( 2) in high (i.e., >90%) yields. The complexes are characterized structurally as 2-D honeycomb-like sheets comprised of edge-shared Mn 12 loops with some noteworthy differences as follows. First, buckling of the 2-D sheet in 1 is not observed for 2, presumably as a consequence of additional intersheet phenyl groups in the latter. Second, complex 1 is comprised of only six-coordinate MnII, while 2 has both pseudo-octahedral and distorted trigonal bipyramidal coordinate metal ions. Third, while complex 2 exhibits pi-stacking interactions with intersheet phenyl-phenyl contacts of 3.285 and 3.369 A, 1 exhibits no such bonding. Antiferromagnetic exchange is observed with Weiss constants (theta) of -28 and -56 K and Neel temperatures of 2.2 and 8.2 K for complexes 1 and 2, respectively. The paramagnetic transition at higher temperatures for complex 2 may be attributed to pi-pi exchange through phenyl groups in adjacent layers. Preliminary gas sorption studies (76 K) indidate preferential adsorption of H2 versus N2 for complex 1 only.     

Large-scale synthesis of thiolated Au25 clusters via ligand exchange reactions of phosphine-stabilized Au11 clusters

Phosphine-stabilized Au11 clusters in chloroform were reacted with glutathione (GSH) in water under a nitrogen atmosphere. The resulting Au:SG clusters exhibit an optical absorption spectrum similar to that of Au25(SG)18, which was isolated as one of the major products from chemically prepared Au:SG clusters (Negishi, Y. et al. J. Am. Chem. Soc. 2005, 127, 5261). Rigorous characterization by optical spectroscopy, electrospray ionization mass spectrometry, and polyacrylamide gel electrophoresis confirms that the Au25(SG)18 clusters were selectively obtained on the sub-100 mg scale by ligand exchange reaction under aerobic conditions. The ligand exchange strategy offers a practical and convenient method of synthesizing thiolated Au25 clusters on a large scale.     

Unusual equilibria involving group 4 amides, silyl complexes, and silyl anions via ligand exchange reactions

Silyl anion SiButPh2- (2) was found to substitute an amide ligand in Zr(NMe2)4 (3) to give the disilyl complex Zr(NMe2)3(SiButPh2)2- (1a) and Zr(NMe2)5- (1b) in THF. The reaction is reversible, and nucleophilic amide NMe2- attacks the Zr-SiButPh2 bonds in 1a or Zr(NMe2)3(SiButPh2) in the reverse reaction, leading to an unusual ligand exchange equilibrium 2 3 + 2 2 right harpoon over left harpoon 1a + 1b (eq 1). The silyl anion 2 selectively attacks the -N(SiMe3)2 ligand in Zr(NMe2)3[N(SiMe3)2] (6) to give 1a and N(SiMe3)2- (7). Reversible reaction occurs as well, where 7 selectively substitutes the silyl ligand in Zr(NMe2)3(SiButPh2)2- (1a) or Zr(NMe2)3(SiButPh2), giving the equilibrium 6 + 2 2 right harpoon over left harpoon 1a + 7 (eq 3). The thermodynamics of these equilibria has been studied: For eq 1, DeltaH degrees = -8.3(0.2) kcal/mol, DeltaS degrees = -23.3(0.9) eu, and DeltaG degrees 298K = -1.4(0.5) kcal/mol at 298 K; for eq 3, DeltaH degrees = -1.61(0.12) kcal/mol, DeltaS degrees = -2.6(0.5) eu, and DeltaG degrees 298K = -0.8(0.3) kcal/mol. In both equilibria, the enthalpy changes for the forward reactions outweigh the entropy changes, and therefore the substitutions of amide ligands in Zr(NMe2)4 (3) and Zr(NMe2)3[N(SiMe3)2] (6) to afford the disilyl complex 1a are thermodynamically favored. The following equilibria were also observed and studied: Zr(NMe2)3[N(SiMe3)2] (6) + Si(SiMe3)3- (9) right harpoon over left harpoon Zr(NMe2)3[Si(SiMe3)3] (10) + N(SiMe3)2- (7) and Zr(NMe2)4 (3) + 9 right harpoon over left harpoon 10 + Zr(NMe2)5- (1b).     

Coordination complexes of the dimethyl-thio-phosphonium cation and ligand exchange

The quantitative exchange of a 4-(dimethylamino)pyridine ligand on the dimethyl-thio-phosphonium cation by Me3P demonstrates the coordinative nature of the N-P and P-P bond and diversifies a fundamentally important new direction in the coordination chemistry of phosphorus as an acceptor.     

Synthesis of aryl- and hetarylphosphonates

The reaction of tris(trimethylsilyl) phosphite with aryl or hetaryl halides under homogeneous catalysis conditions gave bis(trimethylsilyl)phosphonates. Treatment of these products with methanol gave the corresponding arylor hetarylphosphonic acids in quantitative yield.M. V. Lomonosov Moscow State University, 119899 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 10, pp. 2432–2435, October, 1992.     

Coordination and ligand exchange dynamics of solvated metal ions

Recent developments in computer speed and capacity have opened the access to highly accurate molecular dynamics simulations based on quantum mechanically calculated forces for the chemically relevant region around ions in solution (QM/MM formalism). This accuracy, although still extremely consuming (30-300 days of CP time per simulation), is needed for reliable structural details and ligand exchange rates. A large number of main group and transition metal ions have been investigated by this approach, giving very detailed insight into the properties of these ions in solution and allowing to classify the ions by various characteristics. Most first-row transition metal ions have a very stable first hexa-coordinated solvation shell, whose vibrational distortions, however, strongly influence the dynamics of the second shell. The dynamical Jahn-Teller effect - shown to be a femto- and picosecond phenomenon - can strongly influence ligand coordination and exchange dynamics. A large number of ions with very labile solvation shell such as most main group ions, but also transition metal ions, e.g. Ag(I) and Hg(II), can change their coordination within the picosecond scale, leading to an almost simultaneous presence of several species hardly accessible by present experimental techniques. Among these ions, the structure breakers are of particular interest, and it could be shown that there are two types of them, one with a large and very labile first coordination shell such as Cs(I), the other characterised by a small first but an unusually large second solvation shell such as Au(I). Investigations of metal ions coordinated to ammonia ligands have shown that coordination to hetero-atoms can accelerate the ligand exchange reaction rates by several orders of magnitude, e.g. for Cu(II) and Ni(II). Simulations of ions in aqueous ammonia gave a very detailed picture of the complexity of species almost simultaneously present and illustrate the enormous difficulties encountered when trying to fit X-ray or neutron diffraction data for such systems. In general, ligand exchange rates situated in the picosecond range are far below the NMR scale, and as femtosecond laser pulse spectroscopy could not be applied so far to ionic solutions, accurate simulations have become a very important tool to access structure and dynamics of solvated ions. A number of VIDEO clips supplied on the Web as supporting material illustrates the processes occurring in solutions of the metal ions.     

Synthesis of aryl- and hetarylpyrazoles

Hetaryldieneamines (1) react with sulfonyl azides to give 3-hetarylpyrazoles (5). Similarly, N,N-dimethyl-4-phenyldieneamine-2-carboxylic acid methyl ester (6) affords 3-phenylpyrazole-5-carboxylic acid methyl ester (7).

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Synthese von Aryl- und Hetarylpyrazolen (Kurze Mitteilung)

Zusammenfassung Reaktion von Hetaryldienaminen (1) mit Sulfonylaziden führt zu 3-Hetarylpyrazolen (5). N,-N-Dimethyl-4-phenyldienamin-2-carbonsäure-methylester liefert dabei 3-Phenylpyrazol-5-carbonsäure-methylester.

     

Chiral chromatographic separations based on ligand exchange

Taking ligand-exchange chromatographic systems as an example, the effect of the stoichiometry of the solute-chiral selector interaction on the efficiency, selectivity and solute peak profile is discussed. Recent achievements and practical applications of chiral ligand-exchange chromatography are also briefly reviewed.     

Theoretical and experimental investigations of ligand exchange in guanidinate ligand systems for group 13 metals

The ligand exchange of guanidinate ligands between metal centres can play an important role in guanidinate chemistry, and ligand exchange between aluminium centres will form a dimeric intermediate. The synthesis and characterization of the dimer [Me(2)NC(N(i)Pr)(2)](2)Al(2)Cl(4) is reported here: compound crystallizes with a twisted boat conformation of its dimer ring. This compound decomposes to monomers at room temperature over four days, or within 18 hours at 90 degrees C. We undertook a detailed computational characterization of the reaction pathway, which supported the dimer structure and subsequent monomer formation. The ligand exchange route was also exploited for the synthesis of [MeC(N(i)Pr)(2)](2)AlCl, [EtC(N(i)Pr)(2)](2)AlCl, [MeC(N(i)Pr)(2)](2)GaCl, and [Me(2)NC(N(i)Pr)(2)](2)GaCl.     

Enantioselective ligand exchange in modern separation techniques

As a follow-up to a series of review articles on enantioselective ligand exchange chromatography, the present contribution critically evaluates achievements in this area of active and successful research which have been reported in the scientific literature since 1992. Also discussed is enantioselective ligand exchange in electromigration techniques which have developed especially fruitfully during the last decade.     

Mechanistic aspects of ligand exchange in Au nanoparticles

Ligand exchange reaction is a very important and useful tool for preparing functionalised metal nanoparticles. Understanding the mechanism of this process is essential for rational design of nanoparticle-based devices. However the underlying chemistry was found to be very rich. In this article, we summarise the research efforts of several groups to unravel the mechanisms of ligand exchange reaction, and discuss implications for future developments.     

Reaction chemistry and ligand exchange at cadmium-selenide nanocrystal surfaces

The surface chemistry of cadmium selenide nanocrystals, prepared from tri-n-octylphosphine selenide and cadmium octadecylphosphonate in tri-n-octylphosphine oxide, was studied with 1H and {1H}31P NMR spectroscopy as well as ESI-MS and XPS. The identity of the surface ligands was inferred from reaction of nanocrystals with Me3Si-X (X = -S-SiMe3, -Se-SiMe3, -Cl and -S-(CH2CH2O)4OCH3)) and unambiguous assignment of the organic byproducts, O,O'-bis(trimethylsilyl)octadecylphosphonic acid ester and O,O'-bis(trimethylsilyl)ocatdecylphosphonic acid anhydride ester. Nanocrystals isolated from these reactions have undergone exchange of the octadecylphosphonate ligands for -X as was shown by 1H NMR (X = -S-(CH2CH2O)4OCH3) and XPS (X = -Cl). Addition of free thiols to as prepared nanocrystals results in binding of the thiol to the particle surface and quenching of the nanocrystal fluorescence. Isolation of the thiol-ligated nanocrystals shows this chemisorption proceeds without displacement of the octadecylphosphonate ligands, suggesting the presence of unoccupied Lewis-acidic sites on the particle surface. In the presence of added triethylamine, however, the octadecylphosphonate ligands are readily displaced from the particle surface as was shown with 1H and {1H}31P NMR. These results, in conjunction with previous literature reports, indicate that as-prepared nanocrystal surfaces are terminated by X-type binding of octadecylphosphonate moieties to a layer of excess cadmium ions.