Spectroscopic, morphological, and mechanistic investigation of the solvent-promoted aggregation of porphyrins modified in meso-positions by glucosylated steroids.

Solvent-driven aggregation of a series of porphyrin derivatives was studied by UV/Vis and circular dichroism spectroscopy. The porphyrins are characterised by the presence in the meso positions of steroidal moieties further conjugated with glucosyl groups. The presence of these groups makes the investigated macrocycles amphiphilic and soluble in aqueous solvent, namely, dimethyl acetamide/water. Aggregation of the macrocycles is triggered by a change in bulk solvent composition leading to formation of large architectures that express supramolecular chirality, steered by the presence of the stereogenic centres on the periphery of the macrocycles. The aggregation behaviour and chiroptical features of the aggregates are strongly dependent on the number of moieties decorating the periphery of the porphyrin framework. In particular, experimental evidence indicates that the structure of the steroid linker dictates the overall chirality of the supramolecular architectures. Moreover, the porphyrin concentration strongly affects the aggregation mechanism and the CD intensities of the spectra. Notably, AFM investigations reveal strong differences in aggregate morphology that are dependent on the nature of the appended functional groups, and closely in line with the changes in aggregation mechanism. The suprastructures formed at lower concentration show a network of long fibrous structures spanning over tens of micrometres, whereas the aggregates formed at higher concentration have smaller rod-shaped structures that can be recognised as the result of coalescence of smaller globular structures. The fully steroid substituted derivative forms globular structures over the whole concentration range explored. Finally, a rationale for the aggregation phenomena was given by semiempirical calculations at the PM6 level.

Anion recognition in water with use of a neutral uranyl-salophen receptor.

A new water-soluble uranyl-salophen complex incorporating two glucose units has been synthesized. This neutral derivative shows noteworthy binding affinity for fluoride in water thanks to the Lewis acid-base interaction occurring between the metal and the anion. Such interaction is strong enough to overcome the high hydration enthalpy of fluoride. Moreover this complex effectively binds hydrogen phosphate and exhibits remarkably strong association for nucleotide polyanions ADP(3-) and ATP(4-).

Putting the mechanism of the Soai reaction to the test: DFT study of the role of aldehyde and dialkylzinc structure.

Previous DFT calculations provided support to the proposal that the Soai reaction involves a mechanism in which dimer catalysts serve as templates for the reaction of two molecules of dialkylzinc with two molecules of aldehyde so as to reproduce themselves (ref 11). Here it is shown that, from the point of view of formal kinetics, this mechanism can be reduced to a general model, dubbed the extended dimer model, that has the Blackmond-Brown dimer model as a particular case. Depending on the interplay of kinetic constants, the extended dimer model can give rise to either chiral amplification or depletion. Calculations of the kinetic constants at the M05-2X/6-31G(d) level of theory were carried out in order to theoretically evaluate the effect of the second aza group in the six-membered aromatic ring of the aldehydic substrate and the effect of dialkylzinc structure. Predictions of chiral amplification or depletion are in striking agreement with experimental data thus lending support to the proposed mechanism.

Mechanism of the asymmetric autocatalytic Soai reaction studied by density functional theory.

The mechanism of the Soai reaction has been thoroughly investigated at the M05-2X/6-31G(d) level of theory, by considering ten energetically distinct paths. The study indicates the fully enantioselective catalytic cycle of the homochiral dimers to be the dominant mechanism. Two other catalytic cycles are shown to both be important for correct understanding of the Soai reaction. These are the catalytic cycle of the heterochiral dimer and the non-enantioselective catalytic cycle of the homochiral dimers. The former has been proved to be not really competitive with the principal cycle, as required for the Soai reaction to manifest chiral amplification, whereas the latter, which is only slightly competitive with the principal one, nicely explains the experimental enantioselectivity observed in the reaction of 2-methylpyrimidine-5-carbaldehyde. The study has also evidenced the inadequacy of the B3LYP functional for mechanistic investigations of the Soai reaction.

6-Azahemiporphycene: a new member of the porphyrinoid family.

The reaction of 5,10,15-triarylcorrole with 4-amino-4H-1,2,4-triazole provides another example of corrole ring expansion to give the corresponding 6-azahemiporphycene, a novel porphyrin analogue. The facile oxidation of the corrole ring is a required step for the ring expansion and for this reason the reaction fails in the case of corroles bearing meso-phenyl groups carrying electron-withdrawing substituents. Steric requirements also limited the scope of the reaction, which is not successful in the case of 2,6-disubstituted meso-aryl corroles. The occurrence of an initial oxidation is further supported by formation of the 6-azahemiporphycene derivative when the reaction is carried out under the same conditions, using a 5- or a 10-isocorrole as starting material. (1)H NMR spectra and X-ray crystal characterization of 6-azahemiporphycene evidenced the presence of an intramolecular N-H...N hydrogen bond in the inner core of the macrocycle, while photophysical characterization confirmed the aromatic character of the novel macrocycle, showing an intense Soret-like band around 410 nm in the absorption spectrum. The fluorescence emission is very modest, and 6-azahemiporphycene showed higher photostability than the corresponding corrole species. Different metal complexes of 6-azahemiporphycene were prepared following synthetic protocols usually exploited for the preparation of metalloporphyrins, demonstrating good coordination properties for the macrocycle. Both the free-base and metal derivatives were characterized by cyclic voltammetry and spectroelectrochemistry in dichloromethane and benzonitrile. To further detail the behavior of this novel macrocycle, density functional theory (DFT) calculations were carried out on the basic structure of 6-azahemiporphycene with the aim of assessing aromaticity and tautomerism, as well as calculating its stability with respect to the 5-aza isomer.

Amplification of chirality and enantioselectivity in the asymmetric autocatalytic Soai reaction.

From a kinetic analysis of the "dimer model", which is the most prominent mechanism of the Soai reaction, an equation is derived predicting the amplification of enantiomeric excess as a function of initial conditions. The role played by the enantioselectivity of the catalyst-product is also taken into account. Comparison with experimental data obtained at 0 degrees C by Soai et al. shows that the predicted enantiomeric excesses are lower than the experimental values by up to four orders of magnitude, and thus revision of the dimer model in the low-temperature regime is warranted. A kinetic analysis including the formation of tetramers is presented that fits the data at 0 degrees C and indicates that 2:2 heterochiral tetramers are more stable than homochiral and 3:1 heterochiral tetramers. A DFT study on diastereomers of barrel-like tetramers indeed shows higher stability of 2:2 heterochiral tetramers and thus lends support to the above kinetic analysis.

A new water soluble Zn-salophen derivative as a receptor for alpha-aminoacids: unexpected chiral discrimination.

A new water soluble zinc-salophen complex with appended D-glucose moieties was synthesized and characterized. Its binding properties toward six aminoacids were investigated by UV-vis spectrophotometric titrations. Association constants showed to be unfavorably affected by increasing steric hindrance of the side chain. Quite surprisingly, different association constants were measured for the L and D enantiomers. These data suggest that aminoacids are bound via two interactions, zinc-carboxylate coordination and two hydrogen bonds between the ammonium group of the aminoacid and two oxygen atoms of one D-glucose moiety. Such conclusion is supported by the result of semiempirical (PM3) calculations. Notably, the K(L)/K(D) value of 9.6 observed for the association of phenylalanine rivals with the highest values found for the chiral recognition of aminoacids in water.

Specific supramolecular interactions between Zn(2+)-salophen complexes and biologically relevant anions.

Recognition of inorganic phosphates PO(4)(3-), P(2)O(7)(4-), and P(3)O(10)(5-) and nucleotides AMP(2-), ADP(3-), and ATP(4-) by Zn(2+)-salophen complexes 1 and 2 in ethanol was investigated by different spectroscopic techniques. (31)P NMR and mass spectrometry showed that anions of both series are bound by 1 and 2, while absorption and emission studies revealed that only nucleotides produce relevant changes in the spectral properties of the two hosts. (1)H NMR studies proved that the adenine aromatic group is involved in the complexation, thus pointing out the role of supramolecular ditopic receptors played by salophen derivatives toward this class of biologically relevant substrates. The lifetime of the photogenerated triplet state of the Zn(2+)-salophen compounds was measured by nanosecond laser flash photolysis, and the observed changes upon increasing the concentration of nucleotides allowed the identification of the formation of a 1:0.5 host/guest intermediate complex additionally to the formation of a 1:1 complex.

The role of attractive van der Waals forces in the catalysis of Michael addition by a phenyl decorated uranyl-salophen complex.

The Et(3)N-assisted addition of beta-ketoester 3 to MVK in chloroform is catalyzed with high turnover efficiency by the phenyl-substituted uranyl-salophen compound 2b but not by the parent compound 1b. A plausible mechanism is suggested, involving concomitant nucleophilic attack at the beta-carbon and hydrogen bonding between the Et(3)NH(+) countercation and the carbonyl oxygen of the s-cis conformation of the enone reactant. The role of the van der Waals interactions with the aromatic side arm of 2b as a crucial driving force for catalysis is discussed.

Enantiomerization of chiral uranyl-salophen complexes via unprecedented ligand hemilability: toward configurationally stable derivatives.

In the search for configurationally stable inherently chiral uranyl-salophen complexes, the newly synthesized compound 3 featuring a dodecamethylene chain was expected to be a promising candidate. Unexpectedly, dynamic HPLC on a enantioselective column showed that it still undergoes enantiomerization at high temperature. By comparison with the dynamic behavior of compounds 4 and 5, it was found that the enantiomerization rate is independent of the size of the ligand. This finding definitely rules out a jump rope-type mechanism for the enantiomerization process and points to reaction pathways involving preliminary rupture of one of the O...U coordinative bonds. This provides unprecedented evidence of the occurrence of ligand hemilability in metal-sal(oph)en complexes. Such findings inspired the synthesis of compound 6 endowed with a more rigid spacer, i.e., that derived from 4,4'-(1,4-phenylenediisopropylidene)bisphenol. DHPLC investigations showed that the new structural motif imparts a higher configurational stability, thus raising the half-life for the enantiomerization to more than 2 months at room temperature. This clearly establishes that this compound represents the first member of a new class of inherently chiral receptors, whose potential in chiral recognition and catalysis now can be feasibly explored.

A kinetic study of the conjugate addition of benzenethiol to cyclic enones catalyzed by a nonsymmetrical uranyl-salophen complex.

The Et3N-assisted addition of benzenethiol to enones in chloroform is catalyzed with high turnover efficiency by the phenyl-substituted uranyl-salophen compound 3. Catalytic data show a close adherence to a quatermolecular mechanism involving reaction of a base-activated thiol with a reversibly formed complex of enone and metal catalyst, with a complication of product inhibition due to the formation of a product-catalyst complex. The role of the binding energy made available by interactions with the aromatic sidearm of the catalyst is discussed in terms of catalyst-substrate and catalyst-transition state complementarity.

A novel ditopic zinc-salophen macrocycle: a potential two-stationed wheel for [2]-pseudorotaxanes.

Crown ether macrocycle 1 including a zinc-salophen unit is obtained via a de novo synthetic design to give a potential pH-driven two-stationed wheel component of [2]-pseudorotaxane systems.

Inherently chiral uranyl-salophen macrocycles: computer-aided design and resolution.

[structure: see text] A flipping motion rapidly inverts the bent structure of uranyl-salophen compounds and, consequently, causes fast enantiomerization of nonsymmetrically substituted derivatives. This process has been previously slowed by introducing bulky substituents in the imine bond region. Since the resulting complexes dissociate upon chromatographic treatment, an alternative approach to the design and synthesis of robust, nonflipping uranyl-salophen compounds is here described. Such an approach is based on the idea that the flipping motion would be blocked by connecting the para positions with respect to the phenoxide oxygens by means of polymethylene bridges of suitable length. Analysis of a number of uranyl-salophen compounds by molecular mechanics, while showing that bulky substituents in the imine bond region cause severe distortions of the ligand backbone, suggested that the best chain lengths are those that fit the gap between the phenoxide rings without altering the natural geometry of the parent uranyl-salophen compound. Calculations showed that such chains are those composed of 12 and 13 methylene units. Accordingly, chiral uranyl-salophen macrocycles bridged with 12- and 13-methylene chains were synthesized in fairly good yields and resolved by chiral HPLC.

Stereomutations of atropisomers of sterically hindered salophen ligands.

[structure: see text] The stereomutations in nonsymmetrical salophen ligands 1-4 were studied by means of dynamic NMR and HPLC methods. DNMR experiments showed that in DMSO-d(6) hindered ligands 2-4 exist in two chiral conformations, depending on whether the imine carbon atoms are in a cis or trans disposition with respect to the plane of the central o-phenylenediamine ring, the latter being more stable by 1.0 kcal mol(-1). Owing to its higher dipole moment, in the apolar solvent C(6)D(6) the cis conformer is destabilized with respect to the trans one, in agreement with the results of ab initio calculations. In DMSO-d(6) solution the two conformers are in equilibrium through the less hindered rotation about the C6-N7 bond aligned to the a(6,7) axis, and the interconversion barriers range from 18.4 to 19.3 kcal mol(-1). The enantiomerization process is a two step-process that implies sequential rotations around the C6-N7 and the C1-N8 bonds, so that the rate determining step is the slower rotation around the more hindered C1-N8 bond aligned to the a(1,8) axis, and the energy barriers range from 21.4 to 21.9 kcal mol(-1). These values compare well with those determined by chromatography on an enantioselective HPLC column at low temperature, thus confirming that DNMR and DHPLC can be conveniently employed as complementary techniques.

Exclusive transition state stabilization in the supramolecular catalysis of Diels-Alder reaction by a uranyl salophen complex.

Whereas the parent uranyl salophen is catalytically inactive, its phenyl derivative effectively catalyses with turnover the reaction of benzoquinone with 1,3-cyclohexadiene, while showing no appreciable affinity towards reactants and product.

Evaluation of chiral recognition ability of a novel uranyl-salophen-based receptor: an easy and rapid testing protocol.

A novel member of a new class of chiral uranyl-salophen complexes has been synthesised. The chiral recognition ability of this receptor toward the enantiomers of two primary amines, a sulfoxide, and a quaternary ammonium chloride has been evaluated for the first time. The enantioselectivities obtained are encouraging. The NMR method developed for this purpose allows a fast, quantitative determination of the enantioselectivity of the host directly from its racemic mixture and could find application as a preliminary screening tool in the search for new receptors using combinatorial methods. The experiments carried out in this context demonstrated also that the activation barrier for the racemisation of such chiral uranyl-salophen receptors is much higher than the lower limit of 21 kcal mol(-1) previously reported.

Isolation and epimerization kinetics of the first diastereoisomer of an inherently chiral uranyl-salophen complex.

The first diastereoisomeric mixture of an inherently chiral uranyl-salophen complex was prepared using (S)-naproxen as a chiral derivatizing agent. Slow crystallization from diisopropyl ether-chloroform afforded one pure diastereoisomer in 45% yield. Kinetic studies allowed the determination of the epimerization rate. [reaction--see text]

Unprecedented detection of inherent chirality in uranyl-salophen complexes.

In complexes with the uranyl dication salophen ligands are highly puckered. This implies that non-symmetrically substituted uranyl-salophen derivatives exist in principle as a pair of enantiomers. However, due to easy disrotations about the bonds connecting the phenoxide units to the imine carbons, the rate of interconversion between enantiomeric forms of simple, sterically unhindered compounds is extremely fast. Bulky substituents in appropriate positions decrease the interconversion rate and make this novel type of inherent chirality detectable by 1H and 13C NMR.