Efficient synthesis of 2-aminoindane-2-carboxylic acid via dialkylation of nucleophilic glycine equivalent

An efficient, easy to scale-up method for preparing 2-aminoindane-2-carboxylic acid via two-step alkylation of a Ni(II)-complex of glycine Schiff base with 2-[N-(alpha-picolyl)amino]benzophenone (PAAP) (2b) with o-dibromoxylylene (3) is reported. The first step, monoalkylation of 2b with 3, conducted under phase-transfer conditions, gave the corresponding complex 6 in excellent chemical yield (97.2%). Without any purification the intermediate 6 was cyclized under homogeneous conditions (DMF, NaO-t-Bu) to give the product 7 in high chemical yield (93.1%). Decomposition of prepared 7 afforded the target amino acid 2-aminoindane-2-carboxylic acid (1) in 97.9% yield, along with recovery of ligand 8, which was converted back to the starting glycine complex 2b. Operationally convenient experimental procedures, mild reaction conditions, as well as high chemical and volume yields render the method practical for preparing amino acid 1 and its analogues.     

Azidotetrakis(diarylformamidinate)diruthenium(II,III) Compounds: Synthesis,Molecular Structures and Voltammetric Properties; Linear Free Energy Relationships in Dinuclear Compounds VII*<Superscript>,</Superscript>†

A series of Ru₂(DArF)₄(N₃) compounds have been prepared from the metathesis reaction between Ru₂(DArF)₄Cl and NaN₃, where DArF is diarylformamidinate, and aryl is X–Ph with X as 4-MeO (1), 4-Me (2), H (3), 3-MeO (4), 4-Cl (5), 3-Cl (6), 3-CF₃ (7), 4-CF₃ (8), 3,4-Cl₂ (9) and 3,5-Cl₂ (10). Single crystal X-ray diffraction studies of 3 and 10 revealed the expected paddlewheel motif for the first coordination sphere of Ru₂ and axial ligation of azide. Voltammetric studies revealed a (quasi)reversible oxidation (A) and a irreversible reduction (B) for all compounds, and a second (quasi)reduction (C) for compounds 6–10. The half-wave potentials of couple A span a remarkable range of 640 mV, and they correlate linearly with the Hammett constant (σ) of the aryl substituent.¹Dedicated to Professor F. Al Cotton, mentor, friend, and pioneer, on the occasion of his 75th birthday. ²For part VI, see C. Lin, T. Ren, E.J. Valente, and J.D. Zubkowski (1999). J. Organomet. Chem. 579, 114.     

Mapping polypeptide self-recognition through (1)H off-resonance relaxation

1H NMR relaxation rates provide a readily available and sensitive probe ideally suited to investigate the weak (KD approximately micromolar to millimolar range) interactions that frequently mediate polypeptide oligomerization in the early steps of amyloid fibrillogenesis. However, the measurement of transverse and longitudinal 1H relaxation rates is experimentally challenging due to J-transfer and selectivity problems in CPMG and inversion-recovery experiments, respectively. We show here that these problems are effectively circumvented by measuring nonselective off-resonance relaxation rates using an effective field tilted by 35.5 degrees . When applied to the Halpha spins of the Abeta (12-28) peptide, the proposed experiment provides a residue-resolution self-recognition map which is fully consistent with previous independent mutational studies. The method is anticipated to be widely applicable not only to the fast growing family of amyloidogenic peptides but also to the screening and mapping of protein-ligand interactions in general.     

Molecular motions and the structure ofβ-cyclodextrin inclusion complexes with ferrocene, [3]-ferrocenophane-1,3-dione and ruthenocene

Spin-lattice relaxation time measurements in laboratory and rotating frames as well as proton second moment analysis have been used to investigate molecular motions in -cyclodextrin (CD) and its solid inclusion complexes with the title organometallic compounds. Different dynamical processes have been identified in the host lattice along with high mobility of the ferrocene and ruthenocene guest molecules. The Arrhenius parameters of all motions were obtained. The assumption based on the second moment measurements was made about the axial structure of the ferrocene complex and the equatorial one of the ruthenocene complex at low temperatures. The bridged ferrocenophane molecule was shown to be rigid on the NMR time scale. The ternary inclusion complex of -CD with ruthenocene and iodine was also studied and no evidence of redox reactions was observed.     

Antioxidant activity of hydroxystilbene derivatives in homogeneous solution

The antioxidant activity of the cis and trans isomers of several analogues of resveratrol and pterostilbene has been investigated, especially with regard to the effect of the stereochemistry about the olefinic double bond. The antioxidant power of these compounds was estimated by measuring the rate constants for their reactions with peroxyl radicals and, with two of them, the bond dissociation enthalpy (BDE) of the phenolic O-H bond which is cleaved in the inhibition reaction. The present data show that in homogeneous solution the various hydroxystilbenes investigated behave as mild antioxidants with the notable exceptions of the trans isomer of 4 and 6, whose activities are only slightly lower than that of alpha-tocopherol (vitamin E). The rate constants of the inhibition reaction show that the antioxidant activity of the cis-hydroxystilbene is in all the examined cases worse, by a factor ranging between 2 and 6, than that of the corresponding trans isomers. This lower reactivity depends on enthalpy factors as it can be inferred by the experimental values of the O-H bond dissociation enthalpy in the two geometric isomers of 3',5'-di-tert-butyl-4'-hydroxy-3,5-dimethoxystilbene showing that the strength of the O-H bond in the cis isomer is larger by 1.8 kcal/mol. DFT calculations provide a rationalization of this result, indicating that, although the cis geometry implies a destabilization with respect to the trans species of both phenoxyl radical and parent hydroxystilbene, the destabilization of the radical is larger because the folding of the structure strongly reduces the delocalization of the unpaired electron on the styryl group. A comparison of these results with previously reported data on the proapoptotic activity of these stilbenoids suggests that these two properties are not correlated.     

Properties of the silica layer during the formation of MCM-41 studied by EPR of a silica-bound spin probe

The properties of the silica layer during the formation of the mesoporous material MCM-41 were investigated by electron paramagnetic resonance (EPR) experiments carried out on a specifically designed, organo(trialkoxy)silane spin probe, SL1SiEt. Minute amounts of the spin probe were co-condensed with the silica source, tetraethyl orthosilicate (TEOS), in the synthesis of MCM-41 with cetyltrimethylammonium bromide (CTAB) under basic conditions. The mobility and location of the spin probe were followed in the CTAB micellar solution before the reaction, in the reaction mixture and in the final ordered material. It was found that the EPR spectra of hydrolyzed SL1SiEt throughout the room temperature part of the reaction are characteristic of a fast tumbling species, indicating that the silica is highly fluid prior to drying. After filtering, a slow motion type spectrum was observed, showing that the spin-label experiences considerable motional hindrance. The liquidlike behavior could be restored upon stirring the material in water. When the reaction is performed with a hydrothermal stage, the spectrum of SL1SiEt in the final product is the same as that of the room temperature synthesized material, but the addition of water did not restore the high mobility, due to a higher degree of silica cross-linking. The location of SL1SiEt throughout the formation process was obtained from electron spin-echo envelope modulation (ESEEM) measurements on MCM-41 prepared with CTAB deuterated either at the N-methyl or the alpha position and in a reaction carried out in D2O. Comparing the deuterium modulation depth, k(2H), induced by CTAB-alpha-d2, CTAB-d9, or D2O in CTAB micellar solutions of a number of reference spin probes with those of SL1SiEt revealed that the hydrolyzed SL1SiEt is located near the polar heads of the surfactant in the absence of base and TEOS. This supports the postulation of charge matching at the interface as a driving force for the formation of the mesostructure. Similar experiments carried out on reaction mixtures containing SL1SiEt showed a decrease of k(2H) from CTAB-alpha-d2 and CTAB-d9 compared to the micellar solution, exhibiting practically no time dependence. This indicates that the spin probe is pulled away from the micelle-water interface into the loosely linked, forming silica network. After drying, the modulation depth induced by CTAB-alpha-d2 and CTAB-d9 increases, showing that, once the water is removed, the silica walls contract around the micelles, pushing the silica-linked spin probe into the organic phase within the mesopores.     

Cavitand-based nanoscale coordination cages

This communication reports design, self-assembly, solution, and solid-state characterization of nanoscale coordination cages formed by tetradentate cavitand ligands and appropriate metal precursors. The preorganization of the cavitand ligand in terms of structural rigidity and relative orientation of the pyridyl units leads to the exclusive formation of coordination cages in a wide temperature and concentration range. Desired features of the cage self-assembly process, such as reversibility in the presence of a competitive ligand and self-recognition of the cavitand components, have been assessed.     

Preparation and structural characterization of polymer-supported methylrhenium trioxide systems as efficient and selective catalysts for the epoxidation of olefins

Novel heterogeneous compounds of methylrhenium trioxide (MTO) were prepared with poly(4-vinylpyridine) and polystyrene as polymeric supports. The wide-angle X-ray diffraction (WAXS.) analysis, performed by the application of the difference method, showed, in a representative case of the poly(4-vinylpyridine)/MTO derivatives, a slightly distorted octahedral conformation on the metal's primary coordination sphere. The Re-O and Re-C bond distances were not influenced by the polymeric nature of the ligand, while the Re-N bond distance was abnormally shorter than those previously observed for homogeneous MTO/L(n) complexes, showing a strong coordination of the rhenium atom to the support. A set of scanning electron microscopy (SEM) photographs showing the morphology of the surface of particles of poly(4-vinylpyridine)/MTO and polystyrene/MTO systems are reported. The reticulation grade of the polymer was a crucial factor for the morphology of the particles surface. Poly(4-vinylpyridine) 2% cross-linked systems were characterized by particles with very irregular shape and surface. Poly(4-vinylpyridine) 25% cross-linked systems showed particles with regular spherical shape, which morphology was similar to microcapsules obtained with polystyrene. All novel MTO compounds were efficient and selective heterogeneous catalysts for the epoxidation of olefins using environmentally friendly H2O2 as oxygen atom donor. The catalyst activity was maintained for at least five recycling experiments.     

Determination by the EPR Radical Equilibration Technique of the O–H Bond Dissociation Enthalpy in 3,5-Dimethylphenol

The O–H bond dissociation enthalpy (BDE) of 3,5-dimethylphenol has been determined, by using the EPR radical equilibration technique, as 362.5 ± 1.5 kJ/mol. This value is 7 kJ/mol smaller than that of phenol, this indicating that alkyl substitution of the meta hydrogens of phenol induces a weakening of the O–H bond, in contrast with what was reported in a recent calorimetric study.     

Luminescent lanthanide ions hosted in a fluorescent polylysin dendrimer. Antenna-like sensitization of visible and near-infrared emission

We have investigated the complexation of the luminescent Nd(3+), Eu(3+), Gd(3+), Tb(3+), Er(3+), and Yb(3+) ions by a polylysin dendrimer containing 21 amide groups in the interior and, in the periphery, 24 chromophoric dansyl units which show an intense fluorescence band in the visible region. Most of the experiments were performed in 5:1 acetonitrile/dichloromethane solution at 298 K. On addition of the lanthanide ions to dendrimer solutions, the fluorescence of the dansyl units is quenched; in Nd(3+), Er(3+), and Yb(3+), a sensitized near-infrared emission of the lanthanide ion is observed. At low metal ion concentrations, each dendrimer hosts only one metal ion and when the hosted metal ion is Nd(3+) or Eu(3+), the fluorescence of all the 24 dansyl units of the dendrimer is quenched with unitary efficiency. Quantitative measurements were performed in a variety of experimental conditions, including protonation of the dansyl units and measurements in rigid matrix at 77 K where a sensitized Eu(3+) emission could also be observed. The results obtained have been interpreted on the basis of the energy levels and redox potentials of dendrimer and metal ions.