NMR Investigations of the β-Cyclodextrin Inclusion of (α-Phenyl-N-tert-butylnitrone) Analogues

Abstract

Recently, cyclodextrin derivatives were reported to increase significantly the half-life of the spin adducts resulting from the trapping of free radicals with nitrones. To address the physicochemical characteristics of these complexes, a series of α-phenyl-N-tert-butylnitrone (PBN) analogues containing hydroxy groups on the tert-butyl group was prepared. The influence of the substitution on the supramolecular complexation of the nitrones with natural β-cyclodextrin was studied by NMR spectroscopy. 1D-NMR studies indicated a 1:1 stoichiometry and binding constants in the range 32 to 1075 M-1 depending on the substitution pattern. 2D-NMR experiments suggested a competitive inclusion of the PBN derivatives by the aryl moiety through the two accessible wide and narrow rims of the cyclodextrin.

α‐Phenyl‐N‐tert‐butylnitrone‐Type Derivatives Bound to β‐Cyclodextrins: Syntheses, Thermokinetics of Self‐Inclusion and Application to Superoxide Spin‐Trapping

“…Synthesis : α‐Phenyl‐ N ‐ tert ‐butylnitrone (PBN), a linear nitrone, was selected i) for its simplicity for evaluation of the feasibility of preparation of a covalent nitrone–CD system, ii) because of its complementary structure toward the cavity of β‐CD derivatives,11, 14 and iii) to determine the influence of the grafted hosts on the superoxide spin‐trapping properties in relation to those of noncovalent PBN–CD systems. By considering DIMEB and TRIMEB derivatives as macrocyclic hosts, we also expected to favour spin‐adduct complexation over spin‐trap complexation.…”

“…The easy reaction of a hydroxy group, present on the tert ‐butyl part of the 1‐phenyl‐2‐methylpropyl‐1,1‐dimethylethyl‐2‐nitroxide free radical, with disuccinimidyl carbonate (DSC) encouraged us to attempt the direct activation of a hydroxy‐PBN derivative by treatment with DSC 16. Thus, treatment of 1 14 with DSC in acetonitrile in the presence of triethylamine (TEA) afforded the side‐chain activated nitrone 3 (Scheme ). Selective methylation in the 2‐ and the 6‐positions of cyclodextrin derivative 4 17 by a modified Szejtli protocol using dimethyl sulfate in the presence of barium oxide and barium hydroxide, in equivalent volumes of DMF and DMSO, afforded compound 5 .…”

“…Indeed, the absence of any hydrogen bonding network in TRIMEB is correlated with the very small value of K H9 (K H9 = 4 m À1 ) in relation to the previously reported values for DIMEB (K 1 = 80 m À1 ) [11] and natural b-CD (K 1 = 117 m À1 ). [14] NMR study of Me2CD-PBN (7): In the 1 H NMR spectrum of 7 in D 2 O (Figure 2b), the signals of the aromatic protons H 7 and H 8 and the nitronyl proton H 9 are broader than the corresponding signals observed for free PBN in D 2 O (Figure 2a). The 1 H NMR chemical shift of H 9 in compound 7 is significantly shielded, by up to 0.5 ppm, in comparison with the maximum complexation-induced shift (CIS) reported in the noncovalent PBN/DIMEB case (Dd % 0.41 ppm).…”

“…Hence, smaller amounts of CD should be required for complexation of the spin-adduct, which should furthermore be better stabilized because of the greater affinity of the CD cavity towards accommodation of the spin-adduct rather than the nitrone. [11,12] Results and Discussion Synthesis: a-Phenyl-N-tert-butylnitrone (PBN), a linear nitrone, was selected i) for its simplicity for evaluation of the feasibility of preparation of a covalent nitrone-CD system, ii) because of its complementary structure toward the cavity of b-CD derivatives, [11,14] and iii) to determine the influence of the grafted hosts on the superoxide spin-trapping properties in relation to those of noncovalent PBN-CD systems. By considering DIMEB and TRIMEB derivatives as macrocyclic hosts, we also expected to favour spin-adduct complexation over spin-trap complexation.…”

Novel naphthalimide–amine based photoinitiators operating under violet and blue LEDs and usable for various polymerization reactions and synthesis of hydrogels

“…10b). Considering that the observed fluorescence is a weighted contribution of that of free DNND4 and that of complexed DNND4 and using an adapted version for a 1 : 1 binding model (eqn (1)), 56,57 the set of experimental points (intensity measured at 519 nm) was fitted to this equation using a nonlinear curve fit and provided a binding constant K a = 796 ± 60 M −1 (Fig. 10b, inset) which is consistent with expected values: 58,59 F…”