An efficient synthesis of the constrained peptidomimetic 2-oxo-3-(N-9-fluorenyloxycarbonylamino)-1-azabicyclo[4.3.0]nonane-9-carboxylic acid from pyroglutamic acid

[reaction: see text] Azabicyclo[X.Y.0]alkane amino acids are rigid dipeptide mimetics that are useful tools for structure-activity studies in peptide-based drug discovery. Herein, we report an efficient synthesis of three diastereomers of 9-tert-butoxycarbonyl-2-oxo-3-(N-tert-butoxycarbonylamino)-1-azabicyclo[4.3.0]nonane (3S,6S,9S, 3S,6R,9R, and 3S,6R,9S). Methyl N-Boc-pyroglutamate is cleaved with vinylmagnesium bromide to produce an acyclic gamma-vinyl ketone. Michael addition of N-diphenylmethyleneglycine tert-butyl ester produces the N-Boc-delta-oxo-alpha,omega-diaminoazelate intermediate, which, on hydrogenloysis, gives the fused ring system. Acidolytic deprotection followed by Fmoc-protection provided building blocks suitable for solid-phase synthesis.     

Aluminium alkyl and aryloxide complexes of pyrazine and bipyridines: synthesis and structure

The reaction of AlMe(3) and [((t)Bu)(2)Al(micro-OPh)](2) with pyrazine (pyz), 4,4'-bipyridine (4-4'-bipy), 1,2-bis(4-pyridyl)ethane (bpetha) and 1,2-bis(4-pyridyl)ethylene (bpethe) yields (Me(3)Al)(2)(micro-pyz)(1), (Me(3)Al)(2)(micro-4,4'-bipy)(2), (Me(3)Al)(2)(micro-bpetha)(3), (Me(3)Al)(2)(micro-bipethe)(4), Al((t)Bu)(2)(OPh)(pyz)(5), [((t)Bu)(2)Al(OPh)](2)(micro-4,4-bipy)(6a), [((t)Bu)(2)Al(OPh)](2)(micro-bpetha)(7a), [((t)Bu)(2)Al(OPh)](2)(micro-bipethe)(8a). Compounds 1-4, 6a and 7a have been confirmed by X-ray crystallography. In solution compounds 1-4 undergo a rapid ligand-dissociation equilibrium resulting in a time-average spectrum in the (1)H NMR. In contrast, the solution equilibria for compounds 5-8a are sufficiently slow such that the mono-aluminium compounds may be observed by (1)H NMR spectroscopy: Al((t)Bu)(2)(OPh)(4,4-bipy)(6b), Al((t)Bu)(2)(OPh)(bpetha)(7b) and Al((t)Bu)(2)(OPh)(bpethe)(8b). The inability to isolate [((t)Bu)(2)Al(OPh)](2)(micro-pyz) and the relative stability of each complex is discussed with respect to the steric interactions across the bridging ligand (L) and the electronic effect on one Lewis acid-base interaction by the second Lewis acid-base interaction on the same ligand.     

Motion and mixing for multiple ferromagnetic microswimmers

This paper concerns the interaction of several ferromagnetic microswimmers, their motion and the resulting fluid mixing. Each swimmer consists of two ferromagnetic beads joined by an elastic link, and is driven by an external, time-dependent magnetic field. The external field provides a torque on a swimmer and, together with the varying attraction between the magnetic beads, generates a time-irreversible motion leading to persistent swimming in a low Reynolds number environment. The aim of the present paper is to consider the interactions between several swimmers. A regime is considered in which identical swimmers move in the same overall direction, and their motion is synchronised because of driving by the external field. It is found that two swimmers tend to encircle one another while three undergo more complicated motion that may involve the braiding of swimmer trajectories. By means of approximations it is established that the interaction between pairs of swimmers gives circulatory motion which falls off with an inverse square law and is linked to their overall speed of motion through the fluid. As groups of two or more swimmers move through the fluid they process fluid, leaving behind a trail of fluid that has undergone mixing: this is investigated by following streak lines numerically.     

A bridge to coordination isomer selection in lanthanide(III) DOTA-tetraamide complexes

Interest in macrocyclic lanthanide complexes such as DOTA is driven largely through interest in their use as contrast agents for MRI. The lanthanide tetraamide derivatives of DOTA have shown considerable promise as PARACEST agents, taking advantage of the slow water exchange kinetics of this class of complex. We postulated that water exchange in these tetraamide complexes could be slowed even further by introducing a group to sterically encumber the space above the water coordination site, thereby hindering the departure and approach of water molecules to the complex. The ligand 8O2-bridged DOTAM was synthesized in a 34% yield from cyclen. It was found that the lanthanide complexes of this ligand did not possess a water molecule in the inner coordination sphere of the bound lanthanide. The crystal structure of the ytterbium complex revealed that distortions to the coordination sphere were induced by the steric constraints imposed on the complex by the bridging unit. The extent of the distortion was found to increase with increasing ionic radius of the lanthanide ion, eventually resulting in a complete loss of symmetry in the complex. Because this ligand system is bicyclic, the conformation of each ring in the system is constrained by that of the other; in consequence, inclusion of the bridging unit in the complexes means only a twisted square, antiprismatic coordination geometry is observed for lanthanide complexes of 8O2-bridged DOTAM.     

Transport-current-induced unidirectional decrease of spin-wave absorption in a magnet-superconductor structure

The effect of a current on spin-wave propagation in a magnet-superconductor layered structure is investigated experimentally. The phenomenon of nonreciprocal “brightening” of the structure is observed. It is shown that this phenomenon is due to the motion of hypervortices of magnetic flux in a Josephson medium. Pis’ma Zh. éksp. Teor. Fiz. 66, No. 1, 49–52 (10 July 1997)     

Deprotonated diindolylmethanes as dianionic analogues of scorpionate bis(pyrazolyl)borate ligands: synthesis and structural characterization of representative titanocene and zirconocene complexes

Deprotonation of di(3-methylindol-2-yl)phenylmethane (L₂H₂) or with two equivalents of ⁿBuLi, followed by reactions with Cp₂TiCl₂ or Cp₂ZrCl₂ yielded complexes . Compounds 1-4 were characterized by NMR spectroscopy, and compounds 1, 3, and 4 were further analyzed by X-ray crystallography and elemental analysis. The molecular structures of 1, 3, and 4 illustrate that chelating di(3-methylindol-2-yl)methanes have a structural relationship to coordinated bis(pyrazolyl)borates.     

Effects of solvent on the relative stability of mono and di-aluminium aryloxide complexes of bipyridines: anomalous behavior of [(tBu)2Al(OPh)]2(mu-4,4-bipy)

The temperature dependence of the solution equilibrium constants for [((t)Bu)(2)Al(OPh)]2(mu-4,4'-bipy)(1a), [((t)Bu)2Al(OPh)](2)(mu-bipetha)(2a, bipetha = 1,2-bis(4-pyridyl)ethane), and [((t)Bu)(2)Al(OPh)]2(mu-bipethe)(3a, bipethe =trans-1,2-bis(4-pyridyl)ethylene) in C6D6 and CDCl(3) allow for the determination of DeltaH and DeltaS for the dissociation of one Al(tBu)2OPh moiety from the bridging ligand, i.e., 2[(tBu)2AL(OPh)]2(mu-L)<==>(K1)2AL(OPh)(tBu)2(L)+[(tBu)2Al(mu-OPh)]2. For compounds and the DeltaH values in C6D6[99(2) kJ mol(-1)(2a) and 109(5) kJ mol(-1)(3a)] and CDCl3[115(5) kJ mol(-1)(2a) and 139(7) kJ mol(-1)(3a)] were found to be inversely proportional with the dielectric constant of the solvent. In contrast, the DeltaH value for 1a in CDCl3 is surprisingly small [14.9(7) kJ mol(-1)] and does not fit with the trends adopted by the bipetha and bipethe derivatives or the value obtained in C6D6[110(2) kJ mol(-1)]. Unlike the other compounds and the C6D6 solutions, the CDCl3 solution of 1a allows for the observation of a second equilibrium 2Al(OPh)(tBu)2(L)<==>(K2)[(tBu)2Al(mu-OPh)]2+2L, for which the DeltaH has been determined [4.5(3) kJ mol(-1)]. This result suggests that in CDCl3 bonding of the second Al(tBu)2OPh moiety to Al(OPh)(tBu)2(4,4'-bipy)(1b) is stabilized by the presence of the first aluminium, which is counter to ab initio calculations that predicts the aluminium in Al(OPh)((t)Bu)2(L) should destabilize the Al-N interaction with a second Al(tBu)2OPh group. The BDE for dissociation of both Al(tBu)2OPh moieties from 1a-3a, and the energy of formation of hydrogen bond interactions with CHCl3, has been calculated by ab initio methods, and no unusual effects are inherent in 1a.     

Synthesis, relaxometric and photophysical properties of a new pH-responsive MRI contrast agent: the effect of other ligating groups on dissociation of a p-nitrophenolic pendant arm

Two gadolinium(III) chelates, GdNP-DO3A (1-methlyene-(p-NitroPhenol)-1,4,7,10-tetraazacycloDOdecane-4,7,10-triAcetate) and GdNP-DO3AM (1-methlyene(p-NitroPhenol)-1,4,7,10-tetraazacycloDOdecane-4,7,10-triacetAMide), containing a single nitrophenolic pendant arm plus either three acetate or three amide pendant arms were synthesized and characterized. The properties of the gadolinium, terbium, and dysprosium complexes of these ligands were examined as a function of pH. The extent and mechanism of the changes in water relaxivity with pH of each gadolinium complex was found to differ substantially for the two complexes. The water relaxivity of Gd(NP-DO3A) increases from 4.1 mM(-1) s(-1) at pH 9 to 7.0 mM(-1) s(-1) at pH 5 as a result of acid-catalyzed dissociation of the nitrophenol from the lanthanide. The nitrophenol group in Gd(NP-DO3AM) does not dissociate from the metal center even at pH 5; therefore, the very modest increase in relaxivity in this complex must be ascribed to an increase in prototropic exchange rate of the bound water and/or phenolic protons.     

Coordination Chemistry of the Nanocluster [HxPMo12O40?H4Mo72Fe30(O2CMe)15O254(H2O)98]

The ligand exchange chemistry for the iron-molybdenum nanocluster [H₂PMo₁₂O₄₀⊂H₄Mo₇₂Fe₃₀(O₂CMe)₁₅O₂₅₄(H₂O)_98-x(EtOH)_x], {Mo₇₂Fe₃₀(Mo₁₂P)}-EtOH, with 3,5-lutidene, 3-butylpyridine, octanol, octanoic acid, 1-hexadecanethiol, tetraethylene glycol, and dodecylbenzenesulfonic acid is reported. The structure of {Mo₇₂Fe₃₀(Mo₁₂P)} is preserved throughout the reaction and TGA analysis indicates between 5 and 15 ligands could be attached per {Mo₇₂Fe₃₀(Mo₁₂P)}. AFM height measurements increase with increased ligand length; however, the apparent particle diameter appears to be smaller than expected as the ligands increase in size consistent with the adopting a non-extended conformation in a similar manner to that observed for self-assembled monolayers.     

Functionalization of SWNTs to facilitate the coordination of metal ions, compounds and clusters

The carboxylate residues of the open ends of aryl-tert-butyl and arylsulfonic acid side-walled functionalized single walled carbon nanotubes (SWNTs) have been investigated for the complexation conditions of the iron-molybdenum cluster [H(x)PMo(12)O(40)CH(4)Mo(72)Fe(30)(O(2)CMe)(15)O(254)(H(2)O)(98)] ("FeMoC"). A range of alternative donor groups for the attachment of FeMoC have been investigated for piranha etched SWNTs, dodecyl side-walled functionalized SWNTs (DD-SWNTs) and ultra-short SWNTs (US-SWNTs), including include pyridines, thiols and phosphines, using coupling reactions to either the carboxylate or hydroxide residues of the SWNTs' open ends. The functionalized SWNTs have been characterized by XPS, uptake of Fe(3+) and, where appropriate, MAS (31)P NMR. The efficacy of binding is dependent on the presence and identity of the ligand moiety. TEM and AFM of the SWNT-FeMoC conjugates show the presence of a 2-3 nm spherical feature on the tip of individual SWNTs.