A 4-state acid-base controlled molecular switch based on a host-guest system.

A novel ZnII funnel complex that presents three phenol functions within a calix[6]arene macrocycle is described. Host-guest studies, monitored by 1H NMR spectroscopy, evaluate the impact of the replacement of three anisole moieties present in a previously described system with phenols. It is now shown that the dicationic complex is responsive to anions, whereas deprotonation of one phenol unit completely inhibits any hosting response. These properties, combined with those of the corresponding protonated ligand, allow us to obtain different molecular switches, and one of them shows guest embedment changes between four different host states, thus giving rise to a rare case of a triple molecular switch.

"Two-Story" Calix[6]arene-Based Zinc and Copper Complexes: Structure, Properties, and O2 Binding.

A new "two-story" calix[6]arene-based ligand was synthesized, and its coordination chemistry was explored. It presents a tren cap connected to the calixarene small rim through three amido spacers. X-ray diffraction studies of its metal complexes revealed a six-coordinate ZnII complex with all of the carbonyl groups of the amido arms bound and a five-coordinate CuII complex with only one amido arm bound. These dicationic complexes were poorly responsive toward exogenous neutral donors, but the amido arms were readily displaced by small anions or deprotonated with a base to give the corresponding monocationic complexes. Cyclic voltammetry in various solvents showed a reversible wave for the CuII/CuI couple at very negative potentials, denoting an electron-rich environment. The reversibility of the system was attributed to the amido arms, which can coordinate the metal center in both its +II and +I redox states. The reversibility was lost upon anion binding to Cu. Upon exposure of the CuI complex to O2 at low temperature, a green species was obtained with a UV-vis signature typical of an end-on superoxide CuII complex. Such a species was proposed to be responsible for oxygen insertion reactions onto the ligand according to the unusual and selective four-electron oxidative pathway previously described with a "one-story" calix[6]tren ligand.

Immobilization of Monolayers Incorporating Cu Funnel Complexes onto Gold Electrodes. Application to the Selective Electrochemical Recognition of Primary Alkylamines in Water.

The immobilization of a copper calix[6]azacryptand funnel complex on gold-modified electrodes is reported. Two different methodologies are described. One is based on alkyne-terminated thiol self-assembled monolayers. The other relies on the electrografting of a calix[4]arene platform bearing diazonium functionalities at its large rim and carboxylic functions at its small rim, which is post-functionalized with alkyne moieties. In both cases, the CuAAC electroclick methodology proved to be the method of choice for grafting the calix[6]azacryptand onto the monolayers. The surface-immobilized complex was fully characterized by surface spectroscopies and electrochemistry in organic and aqueous solvents. The Cu complex displays a well-defined quasi-reversible system in cyclic voltammetry associated with the Cu(II)/Cu(I) redox process. Remarkably, this redox process triggers a powerful selective detection of primary alkylamines in water at a micromolar level, based on a cavitary recognition process.

Biomimetic cavity-based metal complexes.

The design of biomimetic complexes for the modeling of metallo-enzyme active sites is a fruitful strategy for obtaining fundamental information and a better understanding of the molecular mechanisms at work in Nature's chemistry. The classical strategy for modeling metallo-sites relies on the synthesis of metal complexes with polydentate ligands that mimic the coordination environment encountered in the natural systems. However, it is well recognized that metal ion embedment in the proteic cavity has key roles not only in the recognition events but also in generating transient species and directing their reactivity. Hence, this review focuses on an important aspect common to enzymes, which is the presence of a pocket surrounding the metal ion reactive sites. Through selected examples, the following points are stressed: (i) the design of biomimetic cavity-based complexes, (ii) their corresponding host-guest chemistry, with a special focus on problems related to orientation and exchange mechanisms of the ligand within the host, (iii) cavity effects on the metal ion binding properties, including 1st, 2nd, and 3rd coordination spheres and hydrophobic effects and finally (iv) the impact these factors have on the reactivity of embedded metal ions. Important perspectives lie in the use of this knowledge for the development of selective and sensitive probes, new reactions, and green and efficient catalysts with bio-inspired systems.

Coordination of lead(II) in the supramolecular environment provided by a "two-story" calix[6]arene-based N6 ligand.

First insights into the coordination properties and host-guest behavior of a "two story" calix[6]aza-cryptand (1) are described. The ligand is constituted of a triazacyclononane (TACN) cap and three pyridine (PY) spacers connected to the calix[6]arene small rim. The resulting N6 donor site coordinates Pb(II) ions to give complexes that are highly stable. X-ray diffraction structures reveal a hemidirected environment for Pb(II) with strong coordination to the TACN cap and weaker bonds with the three PY residues. A guest molecule, either water or EtOH, sitting in the calixarene macrocycle and hydrogen-bonded to the phenoxyl units at the level of the small rim further stabilizes the complexes through electrostatic interactions with the metal center and the calixarene core. In-depth (1)H NMR studies confirm the host-guest behavior of the complexes in solution, with evidence of embedment of neutral guest molecules such as EtOH, BuOH, and N-Me-formamide. Hence, in spite of the presence of a N6 donor, the calixarene macrocycle can be open to guest interaction, giving rise to seven-coordinate dicationic complexes. Noteworthy also is the flexibility of the macrocycle that allows Pb(II) to adopt its preferred hemidirected environment in spite of the three covalent links connecting the calixarene core to the three PY groups. The flexibility of the system is further illustrated by the possible coordination of an exogenous anionic ligand in the exo position. Hence, compared to the previously described "one story" calix[6]aza-cryptands, ligand 1 displays several similar but also new features that are discussed.

Replacement of a nitrogen by a phosphorus donor in biomimetic copper complexes: a surprising and informative case study with calix[6]arene-based cryptands.

The aim of the paper is to characterize Cu complexes in the P(Ar)N(3) environment provided by ligands derived from triphenylphosphine P(C(6)H(4)CH(2)NHR)(3) and compare their coordination behavior and reactivity with those obtained with all-nitrogen ligands such as tren. It is shown that coordination of the PN(3) ligand (R = iPr) to Cu(I) and Cu(II) leads to complexes whose coordination sphere is hardly controlled as they readily undergo decoordination of either one N or the P donor together with oxidation of the latter. In strong contrast, when grafted on the small rim of a calix[6]arene, the P(Ar)N(3) is geometrically constrained into a tripod that enforces the metal center to remain in the same environment with a P-Cu bond for both oxidation states. These calix[6]PN(3)-based Cu(I) and Cu(II) complexes react readily with exogenous ligands, making a comparison with calix[6]tren-based copper complexes possible. Indeed, reactivity studies in solution highlight very different behaviors. The complex [Cu(calix[6]PN(3))](2+) shows an unusual affinity for weak sigma-donors (e.g., MeCN > EtOH), while the analogous cuprous complex, [Cu(calix[6]PN(3))](+), displays a surprising affinity for hard O-donor ligands (EtOH, DMF), which has never been observed for the tren analogues. Even more surprising is the lack of reactivity of [Cu(calix[6]PN(3))](+) toward dioxygen, which contrasts strongly with the high reactivity of the [Cu(calix[6]tren)](+) complex. In an attempt to explain the observed differences in binding properties and reactivity, Density Functional Theory calculations and electronic spectra simulations were undertaken. They suggest that coordination of the soft P(Ar)(3) center allows to tune the metal ion properties, either by absorbing excess electron density from Cu(I), or by increasing the electronic density of Cu(II). This is due to the simultaneous presence of the phosphorus atom (sigma-donor) in apical position and the aromatic groups (pi-acceptors) bound to the P-atom.

Synthesis of "two-story" calix[6]aza-cryptands.

The first four members of a new family of C(3v)-symmetrical "two-story" calix[6]aza-cryptands have been synthesized. These large funnel shaped aza-ligands are formed through introduction of three aromatic arms as spacers onto the small rim of a calix[6]arene and subsequently capped with the tripodal aza caps tacn [1,3,5-triazacyclononane] or tren [tris(aminoethyl)amine]. A key feature for an efficient final 1:1 macrocyclization appears to be an adequate geometrical fit between the extended calixarene scaffold and the aza caps.

Fixing the conformations of diamineplatinum(II)-GpG chelates: NMR and CD signatures of individual rotamers.

The bulky, asymmetric analog of the antitumor drug cisplatin, [PtCl(2)(tmen)] (tmen = N,N,N'-trimethylethylenediamine), was used to produce crosslinks with the dinucleotide d(GpG), modeling the most frequent lesions that cisplatin and its analogs cause to DNA. The ligand tmen was chosen because it is expected to constrain the guanine cis to the NMe(2) group in the adduct [Pt(tmen){d(GpG)}](+) to an orientation perpendicular to the coordination plane and to stabilize the other guanine in an oblique orientation, thus maintaining a head-to-head geometry typical of cisplatin-d(GpG) crosslinks within single- and double-stranded DNA. Of the four possible combinations of tmen chirality (R or S symmetry of the coordinated NHMe group) and crosslink direction (5'-G bound cis to the secondary or the tertiary amino group of tmen), two isomers were preponderantly formed, [Pt(R-tmen){d(GpG)}](+) with 5'-G bound cis to NMe(2) and [Pt(S-tmen){d(GpG)}](+) with 5'-G bound cis to NHMe. The former was shown to have a right-handed R2 orientation of guanines similar to that found in duplex DNA, whereas the latter had a left-handed L1 orientation that modeled cisplatin-d(GpG) adducts within single-stranded DNA. The R2 rotamer was found to be in an equilibrium (as observed using EXSY spectroscopy) with a minor fraction (< or =4%) of a Delta-HT rotamer related to R2 by rotation of the 3'-G about the Pt-N7 bond. The major rotamers R2 and L1 were isolated using reverse-phase HPLC, and their NMR and CD signatures were compared to those of the corresponding rotamers of the less hindered adduct [Pt(dmen)(GpG)](+) (dmen = N,N-dimethylethylenediamine). From this and other comparisons with previously reported platinum dinucleotide complexes, and from molecular modeling, it could be concluded that both steric repulsion between guanine and substituents of the cis amino group and N-H...O6 hydrogen bonding are significant effects favoring the oblique orientation of one guanine base typical of the HH rotamers of [Pt(diamine){d(GpG)}](+) and [Pt(diamine)(GpG)](+) complexes.