Configurationally Stable Tris(tetrathioaryl)methyl Molecular Propellers

Abstract

Tris(tetrathioaryl)methanols and tris(tetrathioaryl)methanes are direct precursors and metabolites, respectively, of tris(tetrathioaryl)methyl radicals, which are very attractive paramagnetic spin probes for many magnetic resonance applications. Due to steric hindrance, these propeller‐shaped molecules display slow interconversion between their two enantiomeric conformations (right‐handed and left‐handed propeller conformations). Syntheses and HPLC resolutions carried out on a chiral stationary phase have been achieved. The influence of the hybridization of the central carbon atom as well as the para substitutient on the conformational stability were experimentally and theoretically studied. Depending on their particular structure, the free activation energy for the isomerization process determined by kinetics of racemization varies from 24.4 to 26.4 kcal mol–1 and corresponds to racemization half‐lives of 12 and 343 h, respectively. Computational and NOESY/exchange spectroscopy (EXSY) studies are consistent with a two‐ring flip mechanism for the isomerization process of tris(tetrathioaryl)methanols, radicals and tris(tetrathioaryl)methanes.

Triarylmethyl-based biradical as a superoxide probe

“…The bulky aromatic moiety prevents the two conformations from isomerization at room temperature. [23, 24] The TAM covalent linker is stereogenic and gives (P)-(S,S)-(P), (M)-(S,S)-(M) and the identical (P)-(S,S)-(M) = (M)-(SS)-(P) system. HPLC under isocratic conditions shows two peaks with a ratio of 1:3 as a result of a partial resolution of these stereoisomers.…”

Exchange Phenomena in the Electron Paramagnetic Resonance Spectra of the Nitroxyl and Trityl Radicals: Multifunctional Spectroscopy and Imaging of Local Chemical Microenvironment

“…5 Conformational studies using EPR spectroscopy, DFT calculation, and X-ray diffraction have shown that the TAMs adopt a helix conformation (Scheme 2) which protects the central carbon bearing approximately 60% of the unpaired electron spin density 66 and provides helicoidally chirality to the EPR spin probe. 67,68 …”

“…5 Conformational studies using EPR spectroscopy, DFT calculation, and X-ray diffraction have shown that the TAMs adopt a helix conformation (Scheme 2) which protects the central carbon bearing approximately 60% of the unpaired electron spin density 66 and provides helicoidally chirality to the EPR spin probe. 67,68 The EPR spectra of TAMs containing amino- 63 and phosphono-28,64,65 groups exhibit complex EPR spectra therefore making the spectrum simulation and extraction of both functional parameters, pO 2 and pH, challenging. In particular, the EPR spectra of triphosphonated TAM radicals 64,65 (Scheme 5) contain the superposition of four ionic species arising from the independent ionization of three phosphonic groups with slightly different pK a2 (6.4, 6.9, and 7.7) each having different phosphorus hyperfine splitting pattern.…”

Synthesis of Central Chirality-Containing Triarylmethanols and Triarylmethyl Radicals with Extraordinarily Stable Configurations

“…The half-life of racemization for the two enantiomers of the ethyl ester derivative of TAM radical CT-03 was determined to be 343 h in ethyl acetate at room temperature, which was much longer than the value (16.9 h) of the corresponding tetrathiatriarylmethanol under the same condition. 30,31 The introduction of 12 bulky tert-butyl ether groups on the methylene bridges tremendously lengthens its racemization half-life (1.36 years) relative to its analogue with 12 methyl groups (8.4 h). 32 However, the para-substituent on the aryl ring plays a very minor role in the racemization rate.…”

“…32 However, the para-substituent on the aryl ring plays a very minor role in the racemization rate. 31 Interestingly, the para-substituents on the aryl rings change the molecular symmetry of TAM radicals. X-ray crystallographic results showed that the methyl ester derivative of CT-03 exhibits a strict C 3 symmetry, 9 while the C 3 symmetry is broken in the nitro derivative.…”