The proton complex of a diaza-macropentacycle: structure, slow formation, and chirality induction by ion pairing with the optically active 1,1'-binaphthyl-2,2'-diyl phosphate anion.

The protonation of a sterically crowded [N2S6] macropentacycle (1) with 1 equiv of CF3SO3H in CDCl3 is slow and gives the singly (oo(+) [1 x H](+)) and doubly (o(+)o(+) [1 x 2H](2+)) protonated forms as kinetic products, the i(+)o form of [1 x H](+) being the thermodynamic product. i(+)o [1 x H](+) is C3 helically chiral in the solid state and in solution. The barrier to racemization (DeltaG(double dagger)) of the [1 x H](+) propeller is >71 kJ mol(-1). The ammonium proton is encapsulated in the tetrahedral coordination sphere provided by the endo (i) nitrogen bridgehead atom and the three proximal thioether sulfurs, which makes [1 x H](+) a proton complex. Use of the optically active acid (R)-(-)- or (S)-(+)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BNPH) in chloroform allowed us to induce a significant diastereomeric excess (24% de), which produced a detectable ICD. The de was decreased in acetone-d6 (10%), suggesting that the sense of chirality of [1 x H](+) is controlled by ion-pair interactions. Detailed NMR studies allowed us to locate the chiral anion on the endo side of [1 x H](+), in the cavity lined by endo t-Bu groups, and to establish that the rate of anion exchange in [1 x H][(S,R)-(+/-)-BNP] was higher than the rate of propeller inversion of [1 x H](+).

The in, out asymmetric pseudo-triple helical form of a D3h diaza-macropentacycle.

A sterically encumbered [N(2)S(6)] macropentacycle (5) related to diazamacrobicycles and cryptands has been synthesized in 53% yield by the [1+1] condensation reaction between functionalized macrocyclic and macrotricyclic precursors. A macrononacycle (18) resulting from the corresponding [2+2] condensation was isolated in 7% yield from the reaction mixture. Both compounds showed broad features in their room-temperature (1)H NMR spectra, but their maximal average symmetry (D(3h) and D(2h), respectively) was achieved at high temperature (380 K). At low temperature (200 K, CD(2)Cl(2) solution), the macropentacycle is "frozen" to a single asymmetric (C1) conformation on the (1)H NMR time scale, which has also the molecular structure observed in the solid state by X-ray crystallography: pseudo-triple helical ( not equalC(3)) shape, io (in, out) form resulting from the endo/exo configuration at the nitrogen bridgehead atoms, and similar orientations of the tosyl substituents. The solution dynamics of the molecule can be described by coupled bridgehead nitrogen inversion, triple helix symmetrization, and reversal of triple helix handedness, with DeltaGc = 54.2 kJ mol(-1) in CD(2)Cl(2) at 300 K. Adoption of the io form by macropentacycle 5 in the crystal and in solution at low-temperature most probably results from the steric crowding and strain introduced by the [15]ane-N(2)S(2) macrocyclic bridging subunits.

Formation of RACK- and grid-type metallosupramolecular architectures and generation of molecular motion by reversible uncoiling of helical ligand strands.

The interaction of appropriate metal ions (Pb(II), Zn(II)) with helical ligand strands, obtained by hydrazone polycondensation, generates polymetallic supramolecular architectures of rack and grid types, by uncoiling of the ligand. The interconversion between the helical free ligand and the linearly extended ligand in the complexes produces reversible ion-induced, nanomechanical molecular motions of large amplitude. It has been integrated in an acid-base neutralisation fuelled process, which links the extension/contraction of the ligand strands to alternating changes in pH.

N,N'-linked oligoureas as foldamers: chain length requirements for helix formation in protic solvent investigated by circular dichroism, NMR spectroscopy, and molecular dynamics.

N,N'-linked oligoureas with proteinogenic side chains are peptide backbone mimetics belonging to the gamma-peptide lineage. In pyridine, heptamer 4 adopts a stable helical fold reminiscent of the 2.6(14) helical structure proposed for gamma-peptide foldamers. In the present study, we have used a combination of CD and NMR spectroscopies to correlate far-UV chiroptical properties and conformational preferences of oligoureas as a function of chain length from tetramer to nonamer. Both the intensity of the CD spectra and NMR chemical shift differences between alphaCH2 diastereotopic protons experienced a marked increase for oligomers between four and seven residues. No major change in CD spectra occurred between seven and nine residues, thus suggesting that seven residues could be the minimum length required for stabilizing a dominant conformation. Unexpectedly, in-depth NMR conformational investigation of heptamer 4 in CD3OH revealed that the 2.5 helix probably coexists with partially (un)folded conformations and that Z-E urea isomerization occurs, to some degree, along the backbone. Removing unfavorable electrostatic interactions at the amino terminal end of 4 and adding one H-bond acceptor by acylation with alkyl isocyanate (4 --> 7) was found to reinforce the 2.5 helical population. The stability of the 2.5 helical fold in MeOH is further discussed in light of unrestrained molecular dynamics (MD) simulation. Taken together, these new data provide additional insight into the folding propensity of oligoureas in protic solvent and should be of practical value for the design of helical bioactive oligoureas.

Conformational and inframolecular studies of the protonation of adenophostin analogues lacking the adenine moiety.

Four adenophostin analogues lacking the adenine moiety were subjected to 31P- and 1H-NMR titrations in order to determine the acid-base behaviour of the individual ionisable groups of the molecules and the complex interplay of intramolecular interactions resulting from the protonation process. For the two trisphosphorylated compounds, the curve pattern of the phosphorus nuclei corresponds to the superimposition of the titration curves of a monophosphorylated polyol and a polyol carrying two vicinal phosphates, suggesting that the two phosphate moieties behave independently. Also, the general shape of 1H-NMR titration curves of the studied compounds is very close to that of adenophostin A, indicating that the adenine moiety does not specifically interact with the phosphorylated sugar moieties. The curves show, however, that both trisphosphorylated compounds adopt slightly different preferential conformations which could contribute to explain the difference in their affinity for Ins(1,4,5)P3 receptor. Their macroscopic as well as the microscopic protonation constants are higher than those of adenophostin A, indicating that the adenine moiety plays a base-weakening effect on the phosphate groups. Further analysis of the microscopic protonation constants confirms that the compound whose conformation is the closest to that of adenophostin A also shows the highest biological activity. The two bisphosphorylated analogues studied behave very similarly, suggesting that the deletion of the hydroxymethyl group on the pentafuranosyl ring only weakly influences the protonation process of the phosphate groups that bear the glucopyranose moiety.

Synthesis of new porphyrins with peripheral conjugated chelates and their use for the preparation of porphyrin dimers linked by metal ions.

This article describes the preparation of several new porphyrins bearing chelating peripheral groups fully conjugated with the macrocyclic pi-system. Treatment of a 2-nitro-meso-tetraarylporphyrin with phosphite gave a cyclic enamine, whose formylation gave an enaminoaldehyde. The thio analogue was obtained on treatment with Lawesson's reagent. The same reagent was also used to obtain the isomeric thioenaminoketone chelates. A enaminoketone ligand was prepared from a porphyrinic pyrrolone. All these ligands, as internal nickel complexes, could be metalated with palladium to yield porphyrinic dimers. The dimers obtained from enaminoketones and thioketones show a trans geometry, while in the enaminoaldehyde and -thioaldehyde series the cis isomer is thermodynamically favored. The bathochromic shifts of the electronic spectra of the aldehyde-derived dimers illustrate the strong electronic effect of peripheral metalation and dimerization. However, in the case of the pyrrolone-derived ligand, opposite effects were observed, due to partial reconstitution of the porphyrin chromophore on complexation. As with the dimers derived from enaminoketones, the dimers derived from the new ligands show typical splitting (up to 190 mV) of the electrochemical waves confirming large porphyrin-porphyrin interactions.

Self-assembly, structure, and dynamic interconversion of metallosupramolecular architectures generated by Pb(II) binding-induced unfolding of a helical ligand.

The binding of lead(II) cations to the terpyridine-type subunits of the helical ligand 1 leads to the self-assembly of different polynuclear metallosupramolecular architectures of nanometric size. Three different entities are generated and may be interconverted as a function of metal/ligand stoichiometry: a [4 x 4]Pb(16)(II) grid-type array 2, a [4 # 4]Pb(12)(II) double-cross species 4, and an intermediate complex 3. The structures of 2 and 4 have been confirmed by X-ray crystallography; that of 3 is based on NMR spectral data. The interconversion of the three species generates dynamic diversity and represents an expression of constitutional dynamic chemistry. In the course of ion binding, the helical molecules of ligand 1 unwrap to yield fully extended strands arranged in perpendicular fashion in the architectures 2-4 generated. This process amounts to molecular motions in two directions which confer to the present systems characteristics of two-dimensional nanomechanical devices, capable of performing 2D-contraction/extension motions. The triple features of self-organization, dynamic interconversion, and potential addressability displayed by the processes described trace a self-fabrication approach to nanoscience and nanotechnology.

Synthesis, structural characterization, and immunological properties of carbon nanotubes functionalized with peptides.

Carbon nanotubes (NTs) are becoming highly attractive molecules for applications in medicinal chemistry. The main problem of insolubility in aqueous media has been solved by developing a synthetic protocol that allows highly water-soluble carbon NTs to be obtained. As a result, biologically active peptides can be easily linked through a stable covalent bond to carbon NTs. We have demonstrated that a bound peptide from the foot-and-mouth disease virus, corresponding to the 141-159 region of the viral envelope protein VP1, retained the structural integrity and was recognized by monoclonal and polyclonal antibodies. In addition, this peptide-NT conjugate is immunogenic, eliciting antibody responses of the right specificity. Such a system could be greatly advantageous for diagnostic purposes and could find future applications in vaccine delivery.

Metal-metal bonds between group 12 metals and tin: structural characterization of the complete series of Sn-M-Sn (M=Zn, Cd, Hg) heterodimetallic complexes.

Reaction of the lithium triamidostannate [MeSi[SiMe(2)N(p-Tol)](3)SnLi(OEt(2))] (1) with 0.5 molar equivalents of MCl(2) (M=Zn, Cd, Hg) in toluene afforded the corresponding heterodimetallic complexes [MeSi[SiMe(2)N(p-Tol)](3)Sn](2)M [M=Hg (2), Cd (3), and Zn (4)]. The molecular structures of the mercury and cadmium complexes were determined by X-ray diffraction and found to adopt a linear Sn-M-Sn metal-metal bonded array (d(Sn-Hg) 2.6495(2), d(Sn-Cd) 2.6758(1) A), these being the first Hg-Sn and Cd-Sn bonds to be characterized by X-ray diffraction. That the Hg-Sn bonds are shorter than the Cd-Sn bonds in the isomorphous complexes is attributed to relativistic effects in the mercury system. In contrast, the structure of the Zn analogue is unsymmetrical with one stannate unit being Sn-Zn bonded (d(Sn(1)-Zn) 2.5782(4) A), while the Zn(II) atom bridges two amido functions of the second stannate cage, thus representing a second isomeric form of these complexes. The different degree of metal-metal bond polarity is reflected in the (119)Sn NMR chemical shifts of the three complexes. Variable-temperature NMR studies and a series of (1)H ROESY experiments of the cadmium complex 3 in solution revealed a dynamic exchange between the two isomers.

Two-point self-coordination of a dizinc(II) bispyridylporphyrin ruthenium complex leading selectively to a discrete molecular assembly: solution and solid-state characterization.

The dizinc(II) bispyridylporphyrin ruthenium complex trans,cis,cis[RuCl2(CO)2(Zn.4'-cisDPyP)2] (1Zn, 4'-cisDPyP = 5,10-bis(4'-pyridyl)-15,20-diphenylporphyrin) features two donor (the uncoordinated 4'-N(py) atoms) and two acceptor (the Zn atoms) sites and is thus a building block suited for two-point coordination. 1H NMR spectroscopy indicates that 1Zn self-assembles in solution through Zn-4'-N(py) interactions to yield selectively a highly symmetrical discrete species, in which all donor and all acceptor sites of 1Zn are mutually saturated. Single-crystal X-ray analysis established that this adduct is a dimeric species, (1Zn)2, with a global S4 symmetry, in which the four porphyrins have a propeller-like arrangement. The dimeric species (1Zn)2 is a meso form derived from the combination of two 1Zn units with opposite helical chirality. The geometry of this highly symmetrical tetraporphyrin assembly in solution, as determined by NMR spectroscopy, is essentially the same as that found in the solid state. Thus 1Zn is an unprecedented example of metal-containing self-complementary building block that selectively recognizes itself through four Zn-N(py) interactions, and thus yields a very stable and symmetrical dimeric species, (1Zn)2, that features four porphyrins and six metal atoms (two Ru and four Zn).