The entrapment of chiral guests with gated baskets: can a kinetic discrimination of enantiomers be governed through gating?

The capacity of gated hosts for controlling a kinetic discrimination between stereoisomers is yet to be understood. To conduct corresponding studies, however, one needs to develop chiral, but modular and gated hosts. Accordingly, we used computational (RI-BP86/TZVP//RI-BP86/SV(P)) and experimental (NMR/CD/UV/Vis spectroscopy) methods to examine the transfer of chirality in gated baskets. We found that placing stereocenters of the same kind at the rim (R(1) =CH3, so-called bottom) and/or top amide positions (R(2) =sec-butyl) would direct the helical arrangement of the gates into a P or M propeller-like orientation. With the assistance of (1)H NMR spectroscopy, we quantified the intrinsic (thermodynamic) and constrictive (kinetic) binding affinities of (R)- and (S)-1,2-dibromopropane 5 toward baskets (S3b/P)-2, (S3t/M)-3, and (S3bt/P)-4. Interestingly, each basket has a low ( ≤1.3 kcal mol(-1)), but comparable (de<10%) affinity for entrapping enantiomeric (R/S)-5. In terms of the kinetics, basket (S3b/P)-2, with a set of S stereocenters at the bottom and P arrangement of the gates, would capture (R)-5 at a faster rate (kin(R)/kin(S) =2.0±0.2). Basket (S3t/M)-3, with a set of S centers at the top and M arrangement of the gates, however, trapped (S)-5 at a faster rate (kin(R)/kin(S) =0.30±0.05). In light of these findings, basket (S3bt/P)-4, with a set of S stereocenters installed at both top and bottom sites along with a P disposition of the gates, was found to have a lower ability to differentiate between enantiomeric (R/S)-5 (kin(R)/kin(S) =0.8). Evidently, the two sets of stereocenters in this "hybrid" host acted concurrently, each with the opposite effect on the entrapment kinetics. Gated baskets are hereby established to be a prototype for quantifying the kinetic discrimination of enantiomers through gating and elucidating the electronic/steric effects on the process.

A stereodynamic and redox-switchable encapsulation-complex containing a copper ion held by a tris-quinolinyl basket.

We investigated the coordination of Cu(I)/Cu(II) ions to chiral basket (S(3))-1. The results of both experimental and computational studies suggest the formation of a copper redox-switchable system capable of entrapping CH(3)CN.

Design, preparation, and study of catalytic gated baskets.

We report a diastereoselective synthetic method to obtain a family of catalytic molecular baskets containing a spacious cavity (~570 Å(3)). These supramolecular catalysts were envisioned, via the process of gating, to control the access of substrates to the embedded catalytic center and thereby modulate the outcome of chemical reactions. In particular, gated basket 1 comprises a porphyrin "floor" fused to four phthalimide "side walls" each carrying a revolving aromatic "gate". With the assistance of (1)H NMR and UV-vis spectroscopy, we demonstrated that the small 1-methylimidazole guest (12, 94 Å(3)) would coordinate to the interior while the larger 1,5-diadamantylimidazole guest (14, 361 Å(3)) is relegated to the exterior of basket Zn(II)-1. Subsequently, we examined the epoxidation of differently sized and shaped alkenes 18-21 with catalytic baskets 12(in)-Mn(III)-1 and 14(out)-Mn(III)-1 in the presence of the sacrificial oxidant iodosylarene. The epoxidation of cis-stilbene occurred in the cavity of 14(out)-Mn(III)-1 and at the outer face of 12(in)-Mn(III)-1 with the stereoselectivity of the two transformations being somewhat different. Importantly, catalytic basket 14(out)-Mn(III)-1 was capable of kinetically resolving an equimolar mixture of cis-2-octene 20 and cis-cyclooctene 21 via promotion of the transformation in its cavity.

Substrate-mediated fidelity mechanism ensures accurate decoding of proline codons.

Aminoacyl-tRNA synthetases attach specific amino acids to cognate tRNAs. Prolyl-tRNA synthetases are known to mischarge tRNA(Pro) with the smaller amino acid alanine and with cysteine, which is the same size as proline. Quality control in proline codon translation is partly ensured by an editing domain (INS) present in most bacterial prolyl-tRNA synthetases that hydrolyzes smaller Ala-tRNA(Pro) and excludes Pro-tRNA(Pro). In contrast, Cys-tRNA(Pro) is cleared by a freestanding INS domain homolog, YbaK. Here, we have investigated the molecular mechanism of catalysis and substrate recognition by Hemophilus influenzae YbaK using site-directed mutagenesis, enzymatic assays of isosteric substrates and functional group analogs, and computational modeling. These studies together with mass spectrometric characterization of the YbaK-catalyzed reaction products support a novel substrate-assisted mechanism of Cys-tRNA(Pro) deacylation that prevents nonspecific Pro-tRNA(Pro) hydrolysis. Collectively, we propose that the INS and YbaK domains co-evolved distinct mechanisms involving steric exclusion and thiol-specific chemistry, respectively, to ensure accurate decoding of proline codons.

The role of chirality in directing the formation of cup-shaped porphyrins and the coordination characteristics of such hosts.

Cup-shaped porphyrin 1a has four norbornane rings for encircling space and this type of host could be of interest in supramolecular and catalytic chemistry. We used (1)H NMR spectroscopy to investigate the acid-catalyzed (pTsOH in CHCl(3) and TFA in CH(3)CN) condensation of racemic, enantioenriched (80-85 % enantiomeric excess (ee)), and enantiopure (99 % ee) pyrromethanecarbinol 7 into 1a. We found that the oligomerization of racemic 7(rac) would give 1a-d in the ratio different from the statistical one, though a minuscule quantity of 1a (<5 %) formed. The oligomerization of enantioenriched 7 (80-85 % ee), however, led to the formation of greater amounts of 1a (31-47 %) along with other stereoisomers 1b-d. Importantly, pTsOH catalyzed the conversion of enantiopure 7 (99 % ee) into 1a (>95 % diastereomeric excess (de), 25 % overall yield) in CHCl(3) although prolonged reaction times or greater concentration of the catalytic acid gave rise to 1b-d at the expense of 1a. The metallation of 1 a with Zn(OAc)(2) led to the formation of Zn(II) -1 a and we used computational (DFT: RI-BP86/SV(P),TZVP) and experimental ((1)H NMR spectroscopy) methods to study the partitioning of smaller N-methylimidazole 13 (94 Å(3) ) and bigger 1,5-dicyclohexylimidazole 14 (268 Å(3)) between the inner and outer side of the host. We found that bigger 14 was mostly encapsulated (90 %) inside Zn(II) -1 a at 298.0 K, whereas smaller 13 would equally partition between the two sides of the host. Furthermore, the out/in equilibrium was, in the case of 14-Zn(II) -1a, favored by entropy (TΔS°(out/in) =3.5±0.1 kcal mol(-1)) indicating that perhaps differential solvation of the coordinated ligand assisted the encapsulation.

Direct aldol reactions catalyzed by intramolecularly folded prolinamide dendrons: dendrimer effects on stereoselectivity.

Dendritic effects on both the enantioselectivity and diastereoselectivity of the direct aldol reaction were observed for pyridine-2,6-dicarboxamide dendrons terminated with L-prolinamides.