Changes in Protonation Sites of 3-Styryl Derivatives of 7-(dialkylamino)-aza-coumarin Dyes Induced by Cucurbit[7]uril

Abstract

The incorporation of a guest, with different basic sites, into an organized system (host), such as macrocycles, could stabilize, detect, or promote the formation of a certain protomer. In this context, this work aimed to study the influence of cucurbit[7]uril (CB7) on dyes such as 7-(dimethylamino)-aza-coumarins, which have more than one basic site along their molecular structure. For this, three 3-styryl derivatives of 7-(dialkylamino)-aza-coumarin dyes (SAC1-3) were synthesized and characterized by NMR, ESI-HRMS and IR. The spectral behaviour of the SACs in the absence and presence of CB7 was studied. The results showed large shifts in the UV-vis spectrum in acid medium: a hypsochromic shift of ≈5400 cm−1 (SAC1-2) and ≈3500 cm−1 (SAC3) in the absence of CB7 and a bathochromic shift of ≈4500 cm−1 (SAC1-3) in the presence of CB7. The new absorptions at long and short wavelengths were assigned to the corresponding protomers by computational calculations at the density functional theory (DFT) level. Additionally, the binding mode was corroborated by molecular dynamics simulations. Findings revealed that in the presence of CB7 the heterocyclic nitrogen was preferably protonated instead of the dialkylamino group. Namely, CB7 induces a change in the protonation preference at the basic sites of the SACs, as consequence of the molecular recognition by the macrocycle.

Electrospray ionization tandem mass spectrometry of 4‐aryl‐3,4‐dihydrocoumarins

“…Coumarins 1–11 are polyfunctionalized compounds that bear ether (coumarins 3 and 4 ) and ester functional groups and halogen atoms (coumarins 8 , 10 , and 11 ) that may be susceptible to protonation. Protonation at different sites of the coumarin structure produces different protonated regioisomers (i.e., species that differ only in the position at which the proton is attached), which are referred to in this study as “protomers.” 46,47 On the basis of gas‐phase basicity (GB) and proton affinities (PA), Bouchoux et al reported that the carbonyl oxygen is the most susceptible to protonation in the structure of polyfunctionalized molecules containing carbonyl groups or α,β‐unsaturated carbonyl groups 48,49 . Recently, by using DFT calculations, Sun et al demonstrated that the carbonyl oxygen is the most susceptible to protonation in the coumarin structure 31 .…”

Protomer of Imipramine Captured in Cucurbit[7]uril

“…For example, Alcázar et al. reported that the protonation site of an aza -coumarin dye could be altered via CB[7] complexation . Therefore, the observation and characterization of the protomers of multifunctional molecules in host–guest complexes must be conducted to understand the intrinsic recognition and captivation chemistries of targeted molecules.…”

Editorial: Host–guest chemistry of macrocycles— Volume II

“…coumarin derivatives (SACs), which bear two basic sites in their structure (Alcázar et al, 2022). They first synthesized three styrylderived SACs, namely SAC1, SAC2, and SAC3, which were fully characterized by HR ESI-MS, IR, and NMR.…”

“…The complexation of a guest molecule with multiple basic sites and a macrocyclic host could stabilize, probe, or facilitate the formation of a specific protomer. To verify this, Alcázar et al investigated the impact of CB[7] on the synthetic dyes 7-(dialkylamino)-aza-coumarin derivatives (SACs), which bear two basic sites in their structure ( Alcázar et al, 2022 ). They first synthesized three styryl-derived SACs, namely SAC1 , SAC2 , and SAC3 , which were fully characterized by HR ESI-MS, IR, and NMR.…”