Conformational characterization of lanthanide(III)-DOTA complexes by ab initio investigation in vacuo and in aqueous solution

The conformational behavior of four [Ln(DOTA)(H(2)O)](-) systems (Ln = La, Gd, Ho, and Lu) has been characterized by means of ab initio calculations performed in vacuo and in aqueous solution, the latter by using the polarizable continuum model (PCM). Calculated molecular geometries and conformational energies of the [Ln(DOTA)(H(2)O)](-) systems, and interconversion mechanisms, barriers, and (13)C NMR spectra of the [Lu(DOTA)](-) complex are compared with experimental values. For each system, geometry optimizations, performed in vacuo and in solution at the HF/3-21G level and using a 46+4f(n) core electron effective core potential (ECP) for lanthanides, provide two minima corresponding to a square antiprismatic (A) and an inverted antiprismatic (IA) coordination geometry. All the systems are nonacoordinated, with the exception of the IA isomer of the Lu complex that, from in solution calculations, is octacoordinated, in agreement with experimental data. On comparing the in vacuo relative free energies calculated at different theory levels it can be seen that the nonacoordinated species dominates at the beginning of the lanthanide series while the octacoordinated one does so at the end. Furthermore, on passing along the series the IA isomer becomes less and less favored with respect to A and for the Lu complex a stabilization of the IAisomer is observed in solution (but not in vacuo), in agreement with the experimental data. Investigation of the A<-->IA isomerization process in the [Lu(DOTA)](-) system provides two different interconversion mechanisms: a single-step process, involving the simultaneous rotation of the acetate arms, and a multistep path, involving the inversion of the cyclen cycle configuration. While in vacuo the energy barrier for the acetate arm rotation is higher than that involved in the ring inversion (23.1 and 13.1 kcal mol(-)(1) at the B3LYP/6-311G level, respectively), in solution the two mechanisms present comparable barriers (14.7 and 13.5 kcal mol(-)(1)), in fairly good agreement with the experimental values. The NMR shielding constants for the two isomers of the [Lu(DOTA)](-) complex have been calculated by means of the ab initio GIAO and CSGT methods, and using a 46-core-electron ECP for Lu. The calculated (13)C NMR chemical shifts are in close agreement with the experimental values (rms 3.3 ppm, at the HF/6-311G level) and confirm the structural assignment of the two isomers based on experimental NMR spectra in solution. The results demonstrate that our computational approach is able to predict several physicochemical properties of lanthanide complexes, allowing a better characterization of this class of compounds for their application as contrast agents in medical magnetic resonance imaging (MRI).     

Diaryl-2-pyrrolidinemethanols catalyzed enantioselective epoxidation of α,β-enones: new insight into the effect of structural modification of the catalyst on reaction efficiency

Catalytic enantioselective epoxidation of α,β-unsaturated ketones promoted by diaryl-2-pyrrolidinemethanols and tert-butyl hydroperoxide (TBHP) is described. Investigation on structural modifications of the diaryl-2-pyrrolidinemethanols showed that fine tuning of the stereoelectronics of the substituents on the aryl moiety is important to achieve high efficiency. By employing a structurally optimized organocatalyst, significantly reduced loading (10 mol %) can be used to produce the epoxides in high yield and up to 90% ee at room temperature.     

Development of an integrated capillary electrophoresis/sensor for L-ascorbic acid detection

A CE/biosensor for measuring ascorbic acid was developed by coupling a polyaniline optical sensor and capillary electrophoresis (CE). The capillary column was partially modified with a thin film of polyaniline redox sensitive material. Ascorbic acid was detected by monitoring the changes in optical absorbance occurring to the polyaniline film upon the reduction reaction. The sensor response (change in optical absorbance at 650 nm) is proportional to the concentration of ascorbic acid over a range of 2.5-250 mg/L and the response range has shown a clear dependence on the characteristics of the polymerized film. High specificity and sensitivity of the present method, low sample consumption, short times of response (ca. 2 min) and the reproducibility of the results demonstrate that the CE/polyaniline-sensor could be further employed in the study of the relation between the content of L-ascorbic acid in body fluids and clinical parameters, e.g., cell ageing.     

The crucial role of the diphosphine heteroatom X in the stereochemistry and stabilization of the substitution-inert [M(N)(PXP)]2+ metal fragments (M = Tc, Re; PXP = diphosphine ligand)

The nature of the heteroatom X incorporated in the five-membered PXP-diphosphine bridging chain was found to play a primary unit role both in the overall stability and in the stereochemical arrangement of nitrido-containing [M(N)(PXP)](2+) metal fragments (M = Tc, Re). Thus, by mixing PXP ligands with labile [Re(N)Cl(4)](-) and Tc(N)Cl(2)(PPh(3))(2) nitrido precursors in CH(2)Cl(2)/MeOH mixtures, a series of neutral M(N)Cl(2)(PXP) complexes (M = Tc, 1-5; M = Re, 8, 9) was collected. In the resulting distorted octahedrons, PXP adopted facial or meridional coordination, and combination with halide co-ligands produced three different stereochemical arrangements, that is, fac,cis, mer,cis, and mer,trans, depending primarily on the nature of the diphosphine heteroatom X. When X = NH, mer,cis-Tc(N)Cl(2)(PNP1), 1, was the only isomer formed. Alternatively, when a tertiary amine nitrogen (X = NR; R = CH(3), CH(2)CH(2)OCH(3)) was introduced in the bridging chain, fac,cis-M(N)Cl(2)(PN(R)P) complexes (M = Tc, 2, 3; M = Re, 8f) were obtained. Isomerization into the mer,cis-Re(N)Cl(2)(PN(R)P), 8m, species was observed only in the case of rhenium when the tertiary amine group carried the less encumbering methyl substituent. fac,cis-Tc(N)Cl(2)(PSP), 4f, was isolated in the solid state when X = S, but a mixture of fac,cis-Tc(N)Cl(2)(PSP) and mer,trans-Tc(N)Cl(2)(PSP), 4m, isomers was found in equilibrium in the solution state. A similar equilibrium between fac,cis-M(N)Cl(2)(POP) (M = Tc, 5f; M = Re, 9f) and mer,trans-M(N)Cl(2)(POP) (M = Tc, 5m; M = Re, 9m) species was detected in POP-containing complexes. The molecular structure of all of these complexes was assessed by means of conventional physicochemical techniques including multinuclear NMR spectroscopy and X-ray diffraction analysis of representative mer,cis-Tc(N)Cl(2)(PN(H)P), 1, fac,cis-Tc(N)Cl(2)(PSP), 4f, and mer,cis-Re(N)Cl(2)(PN(Me)P), 8m, compounds.     

The experimental electron density distribution in the complex of (E)-1,2-bis(4-pyridyl)ethylene with 1,4-diiodotetrafluorobenzene at 90 K

The experimental electron density of the donor-acceptor complex of (E)-1,2-bis(4-pyridyl)ethylene (bpe) with 1,4-diiodotetrafluorobenzene (F(4)DIB) at 90 K has been determined with the aspherical atom formalism and analyzed by means of the topological theory of molecular structure. The bpe and F(4)DIB molecules are connected by intermolecular I.N bonds into infinite 1D chains. F.H bonds link these chains together to form the crystal assembly. The topological analysis reveals that the Cbond;I bond is of the "closed shell" type. Its bond-critical properties run parallel to those found in metal-metal and metal-ligand bonds of organometallic compounds. The integrated net charges show that the I.N halogen bond has an essentially electrostatic nature. F.F, F.C, and C.C intermolecular interactions, for which a bond path was found, contribute to reinforce the crystal structure.     

Activity of anchored human matrix metalloproteinase-1 catalytic domain on Au (111) surfaces monitored by ESI-MS

Matrix metalloproteinases (MMPs) are a family of Zn-dependent endo-peptidases known for their ability to cleave several components of the extracellular matrix, but which can also cleave many non-matrix proteins. There are many evidences that MMPs are involved in physiological and pathological processes, and a huge effort has been put in the development of possible inhibitors that could reduce the activity of MMPs, as it is clear that the ability to monitor and control such activity plays a pivotal role in the search for potential drugs aimed at finding a cure for several diseases such as pulmonary emphysema, rheumatoid arthritis, fibrotic disorders and cancer.A powerful method currently available to study enzyme-inhibitor interactions is based on the use of the surface plasmon resonance (SPR) technique. When MMP interactions are studied, a procedure by which inhibitors are normally anchored on sensor chips and SPR technique is used in order to study their interaction with MMPs molecules is usually followed. This is because it is currently believed that MMPs cannot be anchored on the sensor-chip surface without losing their activity. However, this approach gives rise to problems, as the anchoring of low-molecular-weight inhibitors on gold surfaces easily affects their ability to interact with MMPs. For this reason, the anchoring of MMPs is highly desirable.A new experimental protocol that couples the Fourier transform-SPR (FT-SPR) technique with electrospray ionization-mass spectroscopy (ESI-MS) is described here for the evaluation of the activity of MMP-1 catalytic domain (cdMMP-1) anchored on gold surfaces. The cdMMP-1 surface coverage is calculated by using FT-SPR and the enzyme activity is estimated by ESI-MS. The proposed method is label-free.     

X-Ray Structure of an Inclusion Compound of 5,5'-Biscalix[4]arene-hexabenzoate with Toluene

The structure of the 1:3 complex between 5,5'-biscalix[4]arene-hexabenzoateand toluene has been determined by a single crystal X-ray diffraction study. Thetwo calix[4]arene subunits of the 5,5'-biscalix[4]arene system are related by aninversion center and are joined by an eclipsed biphenyl para-para linkage. Each calix[4]arene moiety displays a 1,3-alternate conformation and includes a toluene molecule within two opposite benzoate groups, while a third toluene molecule lies close to a crystallographic inversion center.     

New mu-oxo octanuclear complexes of 3d elements stabilized by dialkylcarbamato ligands. Synthesis and X-ray crystal and molecular structures

The octanuclear aggregates M(8)(mu(4)-O)(2)(O(2)CN(i)()Pr(2))(12) [M = Mn(II) 1, Co(II) 2, Ni(II) 3] have been prepared in good yields by controlled hydrolysis of the corresponding metal carbamate precursors [M(O(2)CN(i)()Pr(2))(2)](n)(). X-ray analysis has shown compounds 1-3 to be isostructural. The core of 2 contains two distorted [M(4)O] tetrahedra related by an inversion center. The hexanuclear carbamates M(6)(O(2)CNEt(2))(12) in toluene undergo a metal redistribution process with formation of the hexanuclear carbamates M'(x)M' '(6-x)(O(2)CNEt(2))(12), M' = Co, M' ' = Mn, as evidenced by mass-spectrometric data. In the presence of moisture, the mixed octanuclear carbamates Co(x)Mn(6-x)(MnO)(CoO)(O(2)CNEt(2))(12) were promptly formed and detected by DCI/MS measurements. Mass spectral data of Co(8)(mu(4)-O)(2)(O(2)CN(i)Pr(2))(12) are also reported.     

Mirror-image packing in enantiomer discrimination molecular basis for the enantioselectivity of B.cepacia lipase toward 2-methyl-3-phenyl-1-propanol

Synthetic chemists often exploit the high enantioselectivity of lipases to prepare pure enantiomers of primary alcohols, but the molecular basis for this enantioselectivity is unknown. The crystal structures of two phosphonate transition-state analogs bound to Burkholderia cepacia lipase reveal this molecular basis for a typical primary alcohol: 2-methyl-3-phenyl-1-propanol. The enantiomeric alcohol moieties adopt surprisingly similar orientations, with only subtle differences that make it difficult to predict how to alter enantioselectivity. These structures, along with a survey of previous structures of enzyme bound enantiomers, reveal that binding of enantiomers does not involve an exchange of two substituent positions as most researchers assumed. Instead, the enantiomers adopt mirror-image packing, where three of the four substituents at the stereocenter lie in similar positions. The fourth substituent, hydrogen, points in opposite directions.