Stereochemical Preference of 2'‐Deoxycytidine for Chiral Bis(diamido)‐bridged Basket Resorcin[4]arenes

Abstract

Bis(diamido)-bridged basket resorcin[4]arene (all-S)-1 and its (all-R)-1 enantiomer proved able to interact with 2'-deoxycytidine (2) and pyrimidine nucleoside analogs in dimethyl sulfoxide (DMSO) solution. In such a solvent, the resorcinarene hosts adopt a preferential 1,3-alternate-like conformation, with a larger cavity delimited by two syn 3,5-dimethoxyphenyl moieties, and two external pockets, each delimited by the other 3,5-dimethoxyphenyl group and its diamido arm (the wing). Complexation phenomena were investigated by nuclear magnetic resonance (NMR) methods, including (1)H NMR DOSY and 1D ROESY experiments, and molecular modeling. Heteroassociation constants of [(all-S)-1·2] and [(all-R)-1·2] diastereoisomeric complexes were obtained from diffusion data by single point measurements, and from nonlinear fitting of 1H NMR chemical shifts. Selective proton relaxation rate measurements allowed us to significantly discriminate the two complexes by identifying two different interaction sites of the guest in the resorcin[4]arene host, depending on its configuration.

Chemical, computational and functional insights into the chemical stability of the Hedgehog pathway inhibitor GANT61

“…In parallel, a new singlet peak is formed at 4.04 ppm, which was attributed to the Ph-CH 2 -NH protons of the newly formed hydrolysis product GANT61-D. Notably, the chemical shift of the new peak from GANT61-D was shown to vary in time as the result of H-bond interactions with the buffer, in agreement with literature data 58 , 59 . Based on NMR data acquired up to 48 h of incubation, a kinetic plot was built to show the hydrolysis of GANT61 ( Figure 2(B) ).…”

Synergistic Effects of Trace Amounts of Water in the Enantiodiscrimination Processes by Lipodex E: A Spectroscopic and Computational Investigation

“…[6][7][8][9][10] The easy commercial accessibility of chiral stationary phases for high-performance liquid chromatography / gas chromatography (HPLC/GC) and of chiral auxiliaries for NMR spectroscopy has made these analytical methods very popular and has led to the recognition, especially in chromatography, of the critical dependence of the reproducibility of analytical separations from the presence of intentional additives or unintentional impurities. 20 With the aim of going into detail on this subject, an accurate spectroscopic and computational study was carried out on the effect of the presence of trace amounts of water on the enantiodiscriminating potency of octakis(3-Obutanoyl-2,6-di-O-pentyl)-γ-cyclodextrin (Lipodex E, Scheme 1), 21 which represents one of the most popular cyclodextrinic selectors employed in gas chromatography [22][23][24][25][26] and in sensors. However, interestingly, in some cases a considerable improvement of enantioseparation has been reported by adding trace amounts of water in the mobile phase.…”

“…[13][14][15][16] This aspect may become notably relevant in the case of chiral selectors able to encapsulate small molecules, such as cyclodextrins [17][18][19] and resorcinarenes. 20 With the aim of going into detail on this subject, an accurate spectroscopic and computational study was carried out on the effect of the presence of trace amounts of water on the enantiodiscriminating potency of octakis(3-Obutanoyl-2,6-di-O-pentyl)-γ-cyclodextrin (Lipodex E, Scheme 1), 21 which represents one of the most popular cyclodextrinic selectors employed in gas chromatography [22][23][24][25][26] and in sensors. 27,28 The investigation of enantiodiscrimination processes in the presence and absence of traces of water was conducted by using methyl-2-chloropropionate (MCP, Scheme 1), which is differentiated by the selector, [26][27][28][29]31,32 as probe 30,33 of enantiodiscrimination processes.…”

Hydrolytic inhibition of α-chymotrypsin by 2,8,14,20-tetrakis(d-leucyl-d-valinamido)resorc[4]arenecarboxylic acid: a spectroscopic NMR and computational combined approach

“…Interestingly, the diffusion coefficient of 1-DD is comparable to that measured for analogues resorcin [4]arenes in the same solvent. 14 On these bases, the dipolar interactions detected in the ROESY maps were reliably attributed to intramolecular effects.…”