Isomeric trimethylene and ethylene pendant-armed cross-bridged tetraazamacrocycles and in vitro/in vivo comparisions of their copper(II) complexes

Ethylene cross-bridged tetraamine macrocycles are useful chelators in coordination, catalytic, medicinal, and radiopharmaceutical chemistry. Springborg and co-workers developed trimethylene cross-bridged analogues, although their pendant-armed derivatives received little attention. We report here the synthesis of a bis-carboxymethyl pendant-armed cyclen with a trimethylene cross-bridge (C3B-DO2A) and its isomeric ethylene-cross-bridged homocyclen ligand (CB-TR2A) as well as their copper(II) complexes. The in vitro and in vivo properties of these complexes are compared with respect to their potential application as (64)Cu-radiopharmaceuticals in positron emission tomography (PET imaging). The inertness of Cu-C3B-DO2A to decomplexation is remarkable, exceeding that of Cu-CB-TE2A. Electrochemical reduction of Cu-CB-TR2A is quasi-reversible, whereas that of Cu-C3B-DO2A is irreversible. The reaction conditions for preparing (64)Cu-C3B-DO2A (microwaving at high temperature) are relatively harsh compared to (64)Cu-CB-TR2A (basic ethanol). The in vivo behavior of the (64)Cu complexes was evaluated in normal rats. Rapid and continual clearance of (64)Cu-CB-TR2A through the blood, liver, and kidneys suggests relatively good in vivo stability, albeit inferior to (64)Cu-CB-TE2A. Although (64)Cu-C3B-DO2A clears continually, the initial uptake is high and only about half is excreted within 22 h, suggesting poor stability and transchelation of (64)Cu to proteins in the blood and/or liver. These data suggest that in vitro inertness of a chelator complex may not always be a good indicator of in vivo stability.     

60]Fullerene-based monolayers as neuroprotective biocompatible hybrid materials

Here we report on the surface immobilization of redox-active [60]fullerene derivatives and the consequent neuroprotective effects toward l-glutamate induced excitotoxicity in human derived undifferentiated neuroblastoma cells.     

Are ring currents still useful to rationalize the benzene proton magnetic shielding?

[structure: see text] The conventional interpretation of proton NMR chemical shifts is supported by large basis set ab initio quantum mechanical calculations. The benzene protons are predicted to lie within the deshielding zone defined in terms of the out-of-plane magnetic shielding domain. However, ring currents by themselves are not sufficient to account quantitatively for the observed benzene proton downfield chemical shift. sigma-Electron contributions must also be taken into account. The conventional explanation for the ethyne proton chemical shift is valid.     

Solid-state (15)N CPMAS NMR and computational analysis of ligand hapticity in rhodium(η-diene) poly(pyrazolyl)borate complexes

Novel [Rh(η-diene)Tp(x)] complexes of sterically encumbered Tp(x) ligands (Tp(x) = Tp(4Bo), diene = cod, 1; nbd, 2; Tp(x) = Tp(4Bo,5Me), diene = cod, 3; nbd, 4; Tp(x) = Tp(a,3Me), diene = cod, 5; nbd, 6; Tp(x) = Tp(a*,3Me), diene = cod, 7; nbd, 8) have been prepared by treatment of [Rh(η-diene)(μ-Cl)](2) with TlTp(x) (Tp(x) in general, in detail: Tp(4Bo) = hydrotris(indazol-1-yl)borate, Tp(4Bo,5Me) = hydrotris(5-methyl-indazol-1-yl)borate, Tp(a,3Me) = hydrotris(3-methyl-2H-benz[g]-4,5-dihydroindazol-2-y1)borate, Tp(a*,3Me) = hydrotris(3-methyl-2H-benz[g]indazol-2-yl)borate), and characterized by analytical and spectral data (IR, (1)H, (11)B, and (13)C NMR solution). The structures adopted by [Rh(nbd)Tp(4Bo)] 2, [Rh(cod)Tp(4Bo,5Me)] 3, [Rh(nbd)Tp(a,3Me)] 6, [Rh(nbd)Tp(a*,3Me)] 8, and [Rh(nbd)Tp(a*,3Me*)] 8* (incorporating a borotropomeric ligand), have been investigated. Low steric hindrance between the ligands in 2 and 3 permits κ(3) coordination of the pyrazolylborate while the high steric encumbrance present in 6, 8, and 8* results in κ(2) ligands. The coordination modes of the ligands to the metal have also been established by (15)N CPMAS studies of selected ligands and their corresponding Rh complexes. These spectroscopic data are in agreement with the (15)N chemical shifts obtained by using quantum-chemical methods to assist reliable assignments of the experimental values, affording new insights into the extraction of structural information concerning the hapticity (κ(2) or κ(3)) of the poly(pyrazolyl)borate ligands to the Rh metal.     

Exclusively Heteronuclear NMR Experiments to Obtain Structural and Dynamic Information on Proteins

Provided that ¹³C‐detected NMR experiments are either preferable or complementary to ¹H detection, we report here tools to determine C^α? C′, C′? N, and C^α? H^α residual dipolar couplings on the basis of the CON experiment. The coupling constants determined on ubiquitin are consistent with the subset measured with the ¹H‐detected HNCO sequences. Since the utilization of residual dipolar couplings may depend on the mobility of the involved nuclei, we also provide tools to measure longitudinal and transverse relaxation rates of N and C′. This new set of experiments is a further development of a whole strategy based on ¹³C direct‐detection NMR spectroscopy for the study of biological macromolecules.     

Antioxidant activity of o-bisphenols: the role of intramolecular hydrogen bonding

A kinetic and thermodynamic investigation on the antioxidant activity of 2,2'-methylenebis(6-tert-butyl-4-methylphenol) (2), 2,2'-ethylidenebis(4,6-di-tert-butylphenol) (3), and 4,4'-methylenebis(2,6-di-tert-butylphenol) (4) are reported. EPR studies of the equilibration between 3 or 4 and a reference phenol, and the corresponding phenoxyl radicals, allowed us to determine the O-H bond dissociation enthalpy (BDE) of the O-H bond as 81.2 and 81.1 kcal/mol in 3 and 4, respectively. Despite this similarity, the absolute rate constants for the reaction with peroxyl radicals, determined by autoxidation studies under controlled conditions, indicate that the o-bisphenols 2 and 3 behave as excellent antioxidants while the p-bisphenol 4 is less effective by a factor of 64 and 22, respectively. FT-IR spectroscopy and product studies suggest that the very good antioxidant activity of the o-bisphenols largely arises from both the reduced steric crowding about the hydroxyl group and the stabilization of the aroxyl radical due to the formation of an intramolecular hydrogen bond between the residual OH and the oxygen radical center.     

Mechanistic Origin of the Vibrational Coherence Accompanying the Photoreaction of Biomimetic Molecular Switches

The coherent photoisomerization of a chromophore in condensed phase is a rare process in which light energy is funneled into specific molecular vibrations during electronic relaxation from the excited to the ground state. In this work, we employed ultrafast spectroscopy and computational methods to investigate the molecular origin of the coherent motion accompanying the photoisomerization of indanylidene–pyrroline (IP) molecular switches. UV/Vis femtosecond transient absorption gave evidence for an excited‐ and ground‐state vibrational wave packet, which appears as a general feature of the IP compounds investigated. In close resemblance to the coherent photoisomerization of rhodopsin, the sudden onset of a far‐red‐detuned and rapidly blue‐shifting photoproduct signature indicated that the population arriving on the electronic ground state after nonadiabatic decay through the conical intersection (CI) is still very focused in the form of a vibrational wave packet. Semiclassical trajectories were employed to investigate the reaction mechanism. Their analysis showed that coupled double‐bond twisting and ring inversions, already populated during the excited‐state reactive motion, induced periodic changes in π‐conjugation that modulate the ground‐state absorption after the non‐adiabatic decay. This prediction further supports that the observed ground‐state oscillation results from the reactive motion, which is in line with a biomimetic, coherent photoisomerization scenario. The IP compounds thus appear as a model system to investigate the mechanism of mode‐selective photomechanical energy transduction. The presented mechanism opens new perspectives for energy transduction at the molecular level, with applications to the design of efficient molecular devices.     

Gold‐Catalyzed 1,2‐/1,2‐Bis‐acetoxy Migration of 1,4‐Bis‐propargyl Acetates: A Mechanistic Study

The late transition metal catalyzed rearrangement of propargyl acetates offers an interesting platform for the development of synthetically useful transformations. We have recently shown that gold complexes can catalyze a highly selective tandem 1,2‐/1,2‐bis‐acetoxy migration in 1,4‐bis‐propargyl acetates to form 2,3‐bis‐acetoxy‐1,3‐dienes. In this way, (1Z,3Z)‐ or (1Z,3E)‐ and (1E,3Z)‐1,3‐dienes could be obtained in a stereocontrolled manner depending on the electronic and steric features of the ancillary ligand bound to gold and the substituents at the propargylic positions. In this work, we report an experimental study on the scope of this transformation, plus a detailed theoretical examination of the reaction mechanism, which has revealed the key features responsible for the reaction stereoselectivity. Synthetic applications towards the one‐pot synthesis of quinoxaline heterocycles and tandem Diels–Alder processes have also been devised.     

Preparation,characterization, and structure of zirconium fluoride alkylamino-N,N-bis methylphosphonates: a new design for layered zirconium diphosphonates with a poorly hindered interlayer region

This paper reports the preparation and characterization of the homologous series of layered zirconium fluoride n-alkylamino-N,N-bis methylphosphonates, of general formula ZrF(O(3)PCH(2))(2)NHC(n)H(2n+1) (n = 1, 2, 3, 4, 5, 6, 8, 9, 10), in which the two phosphonic groups of each diphosphonate building block participate in the assembly of a single lamella, because they are joined to zirconium atoms belonging to the same layer. The crystal structure of one of the series of these zirconium diphosphonates, ZrF(O(3)PCH(2))(2)NHC(5)H(11), has been solved "ab initio" by X-ray powder diffraction data. The structure is monoclinic, space group P2(1)/c. The zwitterionic character of the diphosphonate moiety is a distinctive feature which acts as a structure-orienting factor, generating a layer framework which is different from the other structures known for zirconium phosphates and phosphonates. This compound undergoes a phase transition at 117 degrees C which involves a rearrangement of the interlayer alkyl chains. The structure of the high-temperature phase has been refined by the Rietveld method. Because only one organic residue is associated with two phosphonate tetrahedra, a poorly hindered interlayer region is formed, and alkyl chains bonded to adjacent layers are interdigitated. Preliminary experiments have shown that these compounds are able to intercalate organic molecules, such as n-alkanols, from very dilute water solutions.