Cavity Filling and Chirality Effects in Calixarene Threading

2014 - 2015In 2010, the Prof. Neri’s group showed that the calix[6]arene hosts were able to recognize dialkylammonium axles when they were coupled with the weakly coordinating Tetrakis[3,5 bis(triFluoromethyl)Phenyl]Borate (TFPB−) “superweak anion” that gives very loose ion-pairs with dialkylammonium cations in solution.1 These interpenetrated structures have been defined in supramolecular chemistry as pseudorotaxane and can be considered as synthetic precursors of catenane and rotaxane architectures2 which have showed appealing properties as molecular machines3. Interestingly, the threading of directional alkylbenzylammonium guests with calix[6]arene wheels, led to the stereopreference for the endo-alkyl complexation over the endo-benzyl one and this observed stereo-selectivity brought to the definition of the so called “endo-alkyl rule”4. On these basis we have studied the recognition abilities of calix[6]arene derivatives toward alkylbenzylammonium guests bearing aliphatic chains with different shape and length. In particular, we studied the validity of the endo-alkyl rule with alkylbenzylammonium axles bearing alkyl chains with different lengths and using guests bearing branched alkyl chains. Then the thesis work has been extended to the threading of chiral systems. Special attention was paid to the possibility of obtaining, after threading, the chiral recognition of chiral alkylbenzylammonium ions using chiral calix[6]arene derivatives. The investigation techniques chosen for this purpose have been NMR spectroscopy and Mass Spectrometry by means of the "Enantiomer Labelled Method". Finally the search for new and attractive potential chiral hosts resulted in the application of the "p-bromodienone route" for the first time on calix[6]arene derivatives5 and the study of the optical and electronic properties of inherently chiral resorcin[4]arene derivatives. [edited by author]XIV n.s

Study on the Influence of Chirality in the Threading of Calix[6]arene Hosts with Dialkylammonium Axles

The influence of chirality in calixarene threading has been studied by exploiting the “superweak anion approach”. In particular, the formation of chiral pseudo[2]rotaxanes bearing a classical stereogenic center in their axle and/or wheel components has been considered. Two kind of pseudo[2]rotaxane stereoadducts, the “endo-chiral” and “exo-chiral” ones, having the stereogenic center of a cationic axle inside or outside, respectively, the calix-cavity of a chiral calixarene were preferentially formed with specifically designed chiral axles by a fine exploitation of the so-called “endo-alkyl rule” and a newly defined “endo-α-methyl-benzyl rule” (threading of a hexaalkoxycalix[6]arene with a directional (α-methyl-benzyl)benzylammonium axle occurs with an endo-α-methyl-benzyl preference). The obtained pseudorotaxanes were studied in solution by 1D and 2D NMR, and in the gas-phase by means of the enantiomer-labeled (EL) mass spectrometry method, by combining enantiopure hosts with pseudoracemates of one deuterated and one unlabeled chiral axle enantiomer. In both instances, there was not a clear enantiodiscrimination in the threading process with the studied host/guest systems. Possible rationales are given to explain the scarce reciprocal influence between the guest and host chiral centers

Chirality Transfer in a Calixarene-Based Directional Pseudorotaxane Complex

Hexamethoxycalix[6]arene 3 forms a directional pseudorotaxane complex with the chiral axle (S)-(alpha-methyl-benzyl)benzylammonium 2(+). Between the two (endo-chiral)-2(+)@3 and (exo-chiral)-2(+)@3 pseudorotaxane stereoisomers, the former is preferentially formed. This result confirms the validity of the "endo-alpha-methyl-benzyl rule", previously reported by us. DFT calculations suggest that C-H horizontal ellipsis pi interactions between the methyl group of 2(+) and the calixarene aromatic rings, determine the stereoselectivity of the threading process toward the "endo-alpha-methyl-benzyl preference". An amplification of optical rotation is observed upon formation of the pseudorotaxane complex (endo-chiral)-2(+)@3 with respect to free axle 2(+). Thus, the specifical rotation of the 1:1 mixture of chiral 2(+)center dot B(ArF)(4)(-) salt and achiral 3 was augmented upon formation of the pseudorotaxane and DFT calculations were used to rationalize this result

Auditory cortex hypoperfusion: a metabolic hallmark in Beta Thalassemia

Abstract Background Sensorineural hearing loss in beta-thalassemia is common and it is generally associated with iron chelation therapy. However, data are scarce, especially on adult populations, and a possible involvement of the central auditory areas has not been investigated yet. We performed a multicenter cross-sectional audiological and single-center 3Tesla brain perfusion MRI study enrolling 77 transfusion-dependent/non transfusion-dependent adult patients and 56 healthy controls. Pure tone audiometry, demographics, clinical/laboratory and cognitive functioning data were recorded. Results Half of patients (52%) presented with high-frequency hearing deficit, with overt hypoacusia (Pure Tone Average (PTA) > 25 dB) in 35%, irrespective of iron chelation or clinical phenotype. Bilateral voxel clusters of significant relative hypoperfusion were found in the auditory cortex of beta-thalassemia patients, regardless of clinical phenotype. In controls and transfusion-dependent (but not in non-transfusion-dependent) patients, the relative auditory cortex perfusion values increased linearly with age (p < 0.04). Relative auditory cortex perfusion values showed a significant U-shaped correlation with PTA values among hearing loss patients, and a linear correlation with the full scale intelligence quotient (right side p = 0.01, left side p = 0.02) with its domain related to communication skills (right side p = 0.04, left side p = 0.07) in controls but not in beta-thalassemia patients. Audiometric test results did not correlate to cognitive test scores in any subgroup. Conclusions In conclusion, primary auditory cortex perfusion changes are a metabolic hallmark of adult beta-thalassemia, thus suggesting complex remodeling of the hearing function, that occurs regardless of chelation therapy and before clinically manifest hearing loss. The cognitive impact of perfusion changes is intriguing but requires further investigations

Nucleophilic Functionalization of the Calix[6]arene Para- and Meta-Position via p‑Bromodienone Route

It is here demonstrated that the p-bromodienone route, previously reported for calix[4]arenes, is also effective for the functionalization of the calix[6]arene macrocycle. Thus, alcoholic O-nucleophiles can be introduced at the calix[6]arene exo rim. In addition, the reaction of a calix[6]arene p-bromodienone derivative with an actived aromatic substrate, such as resorcinol, led to the first example of a meta-functionalized, inherently chiral calix[6]arene derivativ

Study on the Influence of Chirality in the Threading of Calix[6]arene Hosts with Dialkylammonium Axles

The influence of chirality in calixarene threading has been studied by exploiting the“superweak anion approach”. In particular, the formation of chiral pseudo[2]rotaxanes bearing aclassical stereogenic center in their axle and/or wheel components has been considered. Two kindof pseudo[2]rotaxane stereoadducts, the “endo-chiral” and “exo-chiral” ones, having the stereogeniccenter of a cationic axle inside or outside, respectively, the calix-cavity of a chiral calixarene werepreferentially formed with specifically designed chiral axles by a fine exploitation of the so-called“endo-alkyl rule” and a newly defined “endo-α-methyl-benzyl rule” (threading of a hexaalkoxycalix[6]arenewith a directional (α-methyl-benzyl)benzylammonium axle occurs with anendo-α-methyl-benzyl preference).The obtained pseudorotaxanes were studied in solution by 1D and 2D NMR, and in the gas-phase bymeans of the enantiomer-labeled (EL) mass spectrometry method, by combining enantiopure hostswith pseudoracemates of one deuterated and one unlabeled chiral axle enantiomer. In both instances,there was not a clear enantiodiscrimination in the threading process with the studied host/guestsystems. Possible rationales are given to explain the scarce reciprocal influence between the guestand host chiral centers

Absolute Configuration Assignment of Chiral Resorcin[4]arenes from ECD Spectra

Racemates of five chiral resorcin[4]arenes, four tetra-O-substituted and one hepta-O-substituted, have been resolved by enantioselective HPLC, and their ECD spectra have been recorded online by stopped-flow measurements. The absolute configuration has been assigned by comparison of the experimental ECD spectra with DFT and semiempirical calculations. For the four tetra-O-substituted resorcin[4]arenes, the ECD exciton couplet at longer wavelength depends on the chirality induced in the arene scaffold by the substituents rather than on the precise nature of the substituents themselves. Accordingly, the exciton chirality model with excitons localized on the arene scaffold, here generalized to Cnsymmetry, accurately describes the relationship between stereochemistry and chiroptical properties for this couplet, while its application at shorter wavelengths is unsafe. For the significantly larger hepta-O-substituted system the assignment particularly benefits from the use of the semiempirical ZINDO method