Evidence for complexes of different stoichiometries between organic solvents and cyclodextrins

The influence of the organic solvent on the acid and basic hydrolysis of N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) in the presence of alpha- and beta-cyclodextrins has been studied. The observed rate constant was found to decrease through the formation of an unreactive complex between MNTS and the cyclodextrins. In the presence of dioxane, acetonitrile or DMSO, the inhibitory effect of beta-CD decreased on increasing the proportion of organic cosolvent as a result of a competitive reaction involving the formation of an inclusion complex between beta-CD and the cosolvent. The disparate size of the organic solvent molecules resulted in stoichiometric differences between the complexes; the beta-CD-dioxane and beta-CD-DMSO complexes were 1 : 1 whereas the beta-CD-acetonitrile complex was 1 : 2. The basic and acid hydrolysis of MNTS in the presence of alpha-CD showed a different behavior; thus, the reaction gave both 1 : 1 and 2 : 1 alpha-CD-MNTS complexes, of which only the former was reactive. This result was due to the smaller cavity size of alpha-CD and the consequent decreased penetration of MNTS into the cavity in comparison to beta-CD. The acid hydrolysis of MNTS in the presence of alpha-CD also revealed decreased penetration of MNTS into the cyclodextrin cavity, as evidenced by the bound substrate undergoing acid hydrolysis. In addition, the acid hydrolysis of MNTS in the presence of acetonitrile containing alpha-CD gave 1 : 1 alpha-CD-acetonitrile inclusion complexes, which is consistent with a both a reduced cavity size and previously reported data.     

On-line capillary electrophoresis-mass spectrometry for the analysis of biomolecules

Mass spectrometry (MS) has become a key tool for the characterization of biologically relevant molecules in the last decade. Due to the complexity of most biological samples an upstream separation is essential. Capillary electrophoresis (CE) has gained much interest due to its high separation efficiency, speed, and often complementary selectivity to liquid chromatography. We describe the state-of-the-art of on-line CE-MS for the analysis of molecules of biological origin. The characterization of peptides, including the study of post-translational modifications, intact proteins, oligonucleotides, and related interaction studies are reviewed. Relevant publications are summarized in tables, including some important method parameters. Key applications are discussed with respect to the advantages and limitations of CE-MS. Coupling interfaces, preconcentration techniques, capillary coatings, and the different CE techniques, e.g., capillary zone electrophoresis, capillary isoelectric focusing, capillary gel electrophoresis, etc. are briefly discussed against the background of their bioanalytical applications.     

Photo and electroluminescence of lanthanide(III) complexes

Major classes of coordination compounds used as electroluminescent materials are surveyed, and their advantages and disadvantages are discussed. The strategy of the directed synthesis of lanthanide(III) complexes promising for use as electroluminescent materials is formulated. The results of studies dealing with the design of electroluminescent devices based on europium(III), terbium(III), and thulium(III) complexes are considered.     

Recent applications of capillary electrophoresis-mass spectrometry (CE-MS): CE performing functions beyond separation

Capillary electrophoresis is one of the separation tools commonly used in conjugation with mass spectrometry. Its primary purpose is to resolve the components in a sample mixture prior to mass spectral identification. Moreover, an increasing number of applications reported in the literature involve the use of CE for additional purposes, such as sample preparation and derivatization, and the study of biochemical properties. This review provides an overview on the various roles of CE beyond that of a simple separation tool. While the scope focuses on the area of interest rather than a predefined time period, the majority of the references highlighted were initially published within the past five years.     

Highly-sensitive simultaneous detection of lanthanide(III) ions as kinetically stable aromatic polyaminocarboxylato complexes via capillary electrophoresis using resolution enhancement with carbonate ion

An aromatic polyaminocarboxylate ligand, 1-(4-aminobenzyl)ethylenediamine-N,N,N,N-tetraacetate (ABEDTA), is proposed as a complexing reagent in the pre-capillary mode so as to form kinetically inert Ln(III) complexes, meaning that no added ligand is necessary in alkaline carrier buffer solutions. In addition, highly-sensitive detection is possible through a light-absorbing moiety of an aminobenzyl group in the ligand. The fine-tuning of the electrophoretic mobilities of the Ln-abedta complexes is successfully achieved by adding an auxiliary carbonate ion ligand which alters the charge-to-size ratio of the complexes through fast exchange equilibria in a carrier buffer. In fact, all of the complexes are detectable with very similar analytical sensitivity and acceptable resolution (except for Ln=Sm, Eu, Gd) by using NaOH-borate carrier buffer solution at pH 12.35 with 20 mM of Na₂CO₃. A typical detection limit for Tb(III) ion (to 3) is as low as 0.94 M, which translates to an absolute amount of 9.4 fmol in a 1.0×10^–8 dm^-3 (10 nL) injection.     

Trivalent lanthanide lacunary phosphomolybdate complexes: a structural and spectroscopic study across the series [Ln(PMo11O39)2]11-

We report the syntheses and crystal structures of (NH4)11[Ln(III)(PMo11O39)2.xH2O (where Ln = every trivalent lanthanide cation except promethium) in which two lacunary [PMo11O39]7- anions sandwich an 8-coordinate Ln(III) cation to yield the complex anion, [LnIII(PMo11O39)2]11-. The 14 salts crystallise in two different space groups, C2/c or P1, but the LnIII containing anions are isostructural across the whole series, a very rare example of such a complete study. Solid state and solution 31P NMR, Raman and IR spectroscopies have been used to prove the stability of [Ln(PMo11O39)2]11- in aqueous solution. As expected, the LnIII cation contracts across the series and the Ln-O bond distances decrease uniformly. Interestingly, the splitting in the nu(P-O) mode within the [PMo11O39]7- unit increases uniformly across the series, which we attribute to the stronger interaction with the smaller, higher charge density LnIII cation as the series is traversed. For the 31P NMR measurements a direct comparison of Lanthanide Induced (paramagnetic) Shift could be made with the analogous [P(W11O39)2]11- complexes.     

Dual-emissive complexes: Visible and near-infrared luminescence from bis-pyrenyl lanthanide(III) complexes

The syntheses and photophysical attributes of a range of dual-emissive lanthanide complexes are described. The simple ligand architecture is based upon a diethylenetriaminepentaacetic acid (DTPA) core and appended with two aminopyrenyl chromophores to yield the fluorescent free ligand L^pyr. Reaction of the ligand with Ln(tris-trifluoromethanosulfate) gave the mononuclear complexes Ln · L^pyr (Ln = Nd, Er, Yb). Luminescence studies revealed that the complexes were emissive in both the near-IR and UV–Vis, the latter resulting from pyrene localised emission (λ_em = 390 nm), the former from pyrene-sensitised emission of the lanthanide ion (λ_ex = 337 nm). Time-resolved measurements in the near-IR indicated that the number of coordinated solvent molecules for Nd and Yb was <1, confirming the proposed coordination mode of the octadentate L^pyr. The suitability of pyrene as a sensitiser for near-IR emitting lanthanides was further demonstrated in the rare observation of Er^III emission in a non-deuteriated protic medium.     

Structural analysis of nine-coordinate lanthanide complexes: steric control of the metal-water distance across the series

The structures of 10 isomorphous lanthanide (Ln) complexes of a chiral DOTA tetra-amide ligand (L(1)), [LnL(1)(H(2)O)](CF(3)SO(3))(3).3H(2)O, crystallizing in space group P2(1), have been studied by single-crystal X-ray diffraction. The Ln coordination is a O(4)N(4) square antiprism, the O(4) base of which is capped by an aqua ligand. The sterically demanding position of the latter results in the lengthening of the Ln-OH(2) distance along the Pr to Lu series by 0.06 A (after allowing for the lanthanide contraction). In parallel, the distance between the bound water oxygen and the second-sphere water oxygen is reduced from 3.17 A (Pr) to 3.04 A (Lu), consistent with the enhanced hydrogen bond acceptor ability of the coordinated water oxygen across the series. A Cambridge Structural Database survey of [Ln(H(2)O)(9)](CF(3)SO(3))(3) salts (space group P6(3)/m) and of six reported isostructural complexes of DOTA [L(2)] revealed a similar trend. The implications of the resultant destabilization of the ground state structure for the water interchange process are discussed.     

Non-template synthesis and electrospray mass spectrometric study of some lanthanide(III) complexes

A new cryptand H₃L was synthesized by the direct condensation of tris(2-aminoethyl)amine (tren) with 2,6-diformyl-4-methoxyphenol (dmp) in the absence of a template ion. The complexes [M(H₃L)(NO₃)](NO₃)₂·xH₂O·yMeOH (M=Y, Sm, Nd; x=1–3, y=1,2) were characterized by several physical methods. The behaviours of the ligand and Nd(III) complex were investigated by electrospray mass spectrometry. The Nd(III) cryptate exhibits high thermodynamic and kinetic stability in solution for no cryptate fragmentation peaks were observed. A complex peak formed by the overlap of two species is also observed. The isotopic distributions of peak clusters in the mass spectrum of the Nd(III) cryptate were calculated.     

Modeling lanthanide complexes: sparkle/AM1 parameters for ytterbium (III)

The Sparkle/AM1 model is extended to ytterbium (III) complexes. Thus, a set of 15 complexes, with various representative ligands, chosen to be representative of all complexes of high crystallographic quality (R-factor <0.05 A) in the Cambridge Crystallographic Database, and which possess oxygen and/or nitrogen as coordinating atoms, was used as the training set. In the validation procedure we added 32 more high quality crystallographic structures. For the 47 complexes, the Sparkle/AM1 unsigned mean error for all interatomic distances between the Yb(III) ion and the ligand atoms of the first sphere of coordination is 0.07 A, similar to present-day ab initio/ECP geometry prediction accuracies, and potentially useful for luminescent complex design while being hundreds of times faster.     

Overview on advances in capillary electrophoresis-mass spectrometry of carbohydrates: a tabulated review

The increasing interest for carbohydrates as holder of essential bioinformations has boosted their full characterization through analytical techniques. The intent of this review is to summarize the recent trends regarding on-line and off-line CE-MS coupling for carbohydrate analysis. A statistical survey on the articles that use derivatizing agents as well as on the analyzer and type of instrument coupling (i.e. on- or off-line) is depicted. From a general overview it can be concluded that, whereas derivatization might be useful for the detection of neutral carbohydrates improving separation selectivity with volatile buffers and increasing sensitivity of the MS detection, relatively few works with derivatized carbohydrates were found; this was noticed in particular for glycosides and saccharides carrying ionizable groups, which are normally analyzed without any chemical modification. The most applied coupling is the on-line sheath-liquid interface; for on-line applications, ESI is the sole source used, whilst the most common analyzer is the IT. MS(n) is often exploited, as fragmentation increases the achieved structural information. CE-MS turned out to be mainly used for the analysis of carbohydrates in drug development (i.e. study of oligosaccharides from pathogens, carbohydrate-based drugs and drug metabolites), in nutrition and for characterization of glycans from glycoproteins. The reader will find elucidating tables regarding these recent CE-MS applications, including the main information on the analysis conditions. Comments are meant to help the immediate focus on the usefulness of the analytical technique and predict the difficulties found during analysis and, in case, their overcoming.     

Thermodynamic study of lanthanide(III) complexes with bifunctional monophosphinic acid analogues of H4dota and comparative kinetic study of yttrium(III) complexes

New bifunctional H(4)dota-like ligands with three acetic acid and one phosphinic acid pendant arms and propionate (H(5)do3ap(PrA)) or 4-aminobenzyl (H(4)do3ap(ABn)) reactive groups bound to the phosphorus atom were investigated. Potentiometric studies showed that the ligands have a similar basicity to the parent H(4)dota and the stability constants of their complexes with sodium(i) and selected lanthanide(III) ions are also similar. Formation and acid-assisted decomplexation kinetics of yttrium(III) complexes with a series of H(4)dota-like ligands (H(4)dota and its phosphinic/phosphonic acid analogues) were studied and the reactions are sensitive to a slight modification of the ligand structure. The (2-carboxyethyl)phosphinic acid derivative H(5)do3ap(PrA) and the phosphonic acid ligand H(5)do3ap form complexes faster than H(4)dota. The most kinetically inert complex is that with H(4)do3ap(ABn). Rates of complexation and decomplexation can depend on the ability to transfer proton(s) outside/inside the complex cavity and, therefore, on the hydrophobicity of the ligands. The results demonstrate that the new bifunctional ligands are suitable for labelling biomolecules with yttrium(iii) radioisotopes for utilization in nuclear medicine.     

Density-functional theory structures of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complexes for ions across the lanthanide series

The use of organically chelated lanthanides in diagnosis and treatment is a rapidly growing field in medicine. In order to gain a deeper understanding into the properties of these chelates, particularly spectroscopic, density-functional calculations have been performed on a series of lanthanide ions chelated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. Based on the results of these calculations, it has been concluded that the local symmetry experienced by the chelated lanthanide ion may be treated as being axial, which will make the interpretation of their spectroscopic properties greatly simplified. It has also been suggested that the so-called "capping" water molecule at the ninth coordination position of the lanthanide is hydrogen bonded to the acetate oxygens of the sidearms, rather than coordinated as the ninth ligand of the lanthanide.     

Synthesis and characterization of (octaaryltetraazaporphyrinato)indium(III) complexes for optical limiting

The preparation of (octaaryltetraazaporphyrinato)indium(III) chlorides [aryl = phenyl (5a), p-tert-butylphenyl (6a), p-(trifluoromethyl)phenyl (7a), m-(trifluoromethyl)phenyl (8a)] and their reactions with aryl Grignard reagents XMgBr to give 5b-8b [X = p-(trifluoromethyl)phenyl] and 5c (R = 3,5-difluorophenyl) are described. The characterization of all compounds by UV-vis, FT-IR, and (1)H and (13)C NMR spectroscopy was performed. The hypsochromic shift of all bands in the absorption spectra of complexes 5a-8a is observed in the sequence 6a < 5a < 7a approximately 8a. This is associated with the increasing electron-withdrawing character of the aryl substituents in the periphery of the tetraazaporphyrin macrocycle. Compounds 8a,b are very good soluble in organic solvents with 8a exhibiting the higher photochemical stability among the various synthesized species. The optical limiting (OL) properties of the complexes have been studied and correlated with the structure of the (tetraazaporphyrinato)indium(III) complexes and the electronic nature of the different substituents. In particular, the OL effect at 532 nm increases on going from the series of compounds 5 to the series 8.     

Multinuclear NMR study of lanthanide(III) complexes of 1,2-PDTA in aqueous solution

The complexation of lanthanide(III) cations with 1,2-propanediaminetetraacetate (1,2-PDTA) in aqueous solution has been investigated by ¹⁰Na, ³⁵Cl, ²H and ¹¹O NMR shift measurements. It has been shown that the contact shifts are dominant for ¹⁷O, ¹⁶Cl and ²H (only for the heavier lanthanide series) and the pseudocontact shifts are dominant for ²⁵Na. It is suggested that the 1,2-PDTA ligand is bound pentadentately via the two nitrogens and the three carboxylates for the lighter lanthanide complexes, hexdentately via the two nitrogens and the four carboxylates for the heavier ones. The numbers of the water coordinated were determined. The small amount of chloride anion in inner coordination sphere was observed.     

Ion-pair interactions of lanthanide(III) complexes in aqueous solutions

The formation of ion-pair adducts between the cationic complex La(THP)3+ (THP = 1,4,7,10-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane) and the anionic complexes Tm(DOTA)- (DOTA = 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetate), Tm(DTPA)2- (DTPA = diethylenetriamine-N,N,N',N",N"-pentaacetate), Tm(TTHA)3- (TTHA = triethylenetetraamine-N,N,N',N",N"',N"'-hexaacetate), and Tm(DOTP)5- (DOTP = 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetrakis(methylenephosphonate)) is examined by 13C NMR spectroscopy. The induced 13C shifts of the La(THP)3+ complex are followed by titration of the Tm(III) complexes of DOTA, DTPA, and TTHA at pH 7. From these data, the stability constants are calculated to be beta 1 = 64 M-1 (1:1), beta 1 = 296 M-1 (1:1), and beta 2 = 26,000 M-2 (2:1) for the ion pairs of La(THP)3+, with Tm(DOTA)-, Tm(DTPA)2-, and Tm(TTHA)3-, respectively. The La(THP)3+,Tm(DOTP)5- system elicits chiral resolution of the rapidly interconverting Tm(DOTP)5- isomers.     

No-alignment-strategies for exploring a set of two-way data tables obtained from capillary electrophoresis-mass spectrometry

Hyphenated techniques such as capillary electrophoresis-mass spectrometry (CE-MS) or high-performance liquid chromatography with diode array detection (HPLC-DAD), etc., are known to produce a huge amount of data since each sample is characterized by a two-way data table. In this paper different ways of obtaining sample-related information from a set of such tables are discussed. Working with original data requires alignment techniques due to time shifts caused by unavoidable variations in separation conditions. Other pre-processing techniques have been suggested to facilitate comparison among samples without prior peak alignment, for example, 'binning' and/or 'blurring' the data along the time dimension. All these techniques, however, require optimization of some parameters, and in this paper an alternative parameter-free method is proposed. The individual data tables (X) are represented as Gram matrices (XXT), where the summation is taken over the time dimension. Hence the possible variations in time scale are eliminated, while the time information is at least partly preserved by the correlation structure between the detection channels. For comparison among samples, a similarity matrix is constructed and explored by principal component analysis and hierarchical clustering. The Gram matrix approach was tested and compared to some other methods using 'binned' and 'blurred' data for a data set with CE-MS runs on urine samples. In addition to data exploration by principal component analysis and hierarchical clustering, a discriminant partial least squares model was constructed to discriminate between the samples that were taken with and without the prior intake of a drug. The result showed that the proposed method is at least as good as the others with respect to cluster identification and class prediction. A distinct advantage is that there is no need for parameter optimization, while a potential drawback is the large size of the Gram matrices for data with high mass resolution.     

Protein binding to lanthanide(III) complexes can reduce the water exchange rate at the lanthanide

The GdIII-based magnetic resonance imaging contrast agent MS-325 targets the blood protein serum albumin, resulting in an increased efficacy (relaxivity) as a relaxation agent. MS-325 showed different relaxivities when bound to serum albumin from different species, e.g., r1=30.5 mM-1 s-1 (rabbit) vs 46.3 mM-1 s-1 (human) at 35 degrees C and 0.47 T. To investigate the mechanism for this difference, surrogate complexes were prepared where the GdIII ion was replaced by other LnIII ions. Fluorescence lifetime measurements of the EuIII analogue indicated that the hydration number was q=1 and did not change when bound to either human, rat, rabbit, pig, or dog serum albumin. The YbIII analogue, YbL1, was prepared and characterized by 1H NMR. Line-shape analysis of the paramagnetic-shifted 1H NMR resonances in the presence of increasing amounts of human (HSA) or rabbit (RSA) serum albumin allowed estimation of the transverse relaxation rate, R2, of these resonances for the protein-bound YbL1. The rotational correlation time of YbL1 was calculated from R2, and the Yb-H distance and was tauR=8+/-1 ns when bound to HSA and 13+/-2 ns when bound to RSA. The water exchange rate at the DyIII analogue, DyL1, was determined from variable-temperature R2 measurements at 9.4 T when DyL1 was bound to either HSA or RSA. At 37 degrees C, water exchange at DyL1 was (31+/-5)x10(6) s-1 when bound to HSA but (3.8+/-0.2)x10(6) s-1 when bound to RSA. Slower water exchange upon RSA binding explains the differences in relaxivity observed. The approach of using surrogate lanthanides to identify specific molecular parameters influencing relaxivity is applicable to other protein-targeted GdIII contrast agents.     

Sparkle model for the calculation of lanthanide complexes: AM1 parameters for Eu(III), Gd(III), and Tb(III)

Our previously defined Sparkle model (Inorg. Chem. 2004, 43, 2346) has been reparameterized for Eu(III) as well as newly parameterized for Gd(III) and Tb(III). The parameterizations have been carried out in a much more extensive manner, aimed at producing a new, more accurate model called Sparkle/AM1, mainly for the vast majority of all Eu(III), Gd(III), and Tb(III) complexes, which possess oxygen or nitrogen as coordinating atoms. All such complexes, which comprise 80% of all geometries present in the Cambridge Structural Database for each of the three ions, were classified into seven groups. These were regarded as a "basis" of chemical ambiance around a lanthanide, which could span the various types of ligand environments the lanthanide ion could be subjected to in any arbitrary complex where the lanthanide ion is coordinated to nitrogen or oxygen atoms. From these seven groups, 15 complexes were selected, which were defined as the parameterization set and then were used with a numerical multidimensional nonlinear optimization to find the best parameter set for reproducing chemical properties. The new parameterizations yielded an unsigned mean error for all interatomic distances between the Eu(III) ion and the ligand atoms of the first sphere of coordination (for the 96 complexes considered in the present paper) of 0.09 A, an improvement over the value of 0.28 A for the previous model and the value of 0.68 A for the first model (Chem. Phys. Lett. 1994, 227, 349). Similar accuracies have been achieved for Gd(III) (0.07 A, 70 complexes) and Tb(III) (0.07 A, 42 complexes). Qualitative improvements have been obtained as well; nitrates now coordinate correctly as bidentate ligands. The results, therefore, indicate that Eu(III), Gd(III), and Tb(III) Sparkle/AM1 calculations possess geometry prediction accuracies for lanthanide complexes with oxygen or nitrogen atoms in the coordination polyhedron that are competitive with present day ab initio/effective core potential calculations, while being hundreds of times faster.