Multiple Reversible Dynamics of Pyrimidine Based Acylhydrazones

Abstract

We employed (Z)‐N'‐[phenyl(pyrimidin‐2‐yl)methylene]nicotinohydrazide (2) and (Z)‐4‐(dimethylamino)‐N'‐[phenyl(pyrimidin‐2‐yl)methylene]benzohydrazide (3) as cores of dynamic chemical systems whose different states are modulated, in a reversible fashion, through specific physical and chemical stimuli. The structure of the compounds was determined by Nuclear Magnetic Resonance (NMR) techniques (1D and 2D) and confirmed by single‐crystal X‐ray diffraction. By Variable temperature (VT) 1H NMR experiments and DFT calculations, the conformational isomerism of 2 was studied and added as an additional input for the dynamic system. Additionally, 2 exhibits configurational E/Z isomerization mediated by pH variations and UV light. On the other hand, configurational isomerism locks an unlocks a tridentate pocket for metal cation coordination in both 2 and 3. All the different dynamic states configurational/conformational isomerism and locked and unlocked coordination constitute a development in the field of systems of multiple dynamics suitable for molecular machines.

Versatility of the Amino Group in Hydrazone‐Based Molecular and Supramolecular Systems

“…Hydrazones experience E/Z isomerism, similar to the imines ( C=N ), where the presence of an additional nitrogen atom decreases the double‐bond character of the π‐system and facilitates isomerization [59] . They can be either photochemically or thermally activated and are usually facilitated by polar solvents, acid/base catalysts, or by electron‐donating substituents [12,59–61] . The uncatalyzed isomerization around the C=N bond is known to proceed via two different mechanisms: rotation (via a polar transition state) and inversion (via a nonpolar transition state) (Scheme 8).…”

“…[59] They can be either photochemically or thermally activated and are usually facilitated by polar solvents, acid/base catalysts, or by electron-donating substituents. [12,[59][60][61] The uncatalyzed isomerization around the C=N bond is known to proceed via two different mechanisms: rotation (via a polar transition state) and inversion (via a nonpolar transition state) (Scheme 8). [62][63][64] Beyond the details of how isomerization proceeds, the configurational dynamic is attractive because the interconversion between two states offers the possibility of the development of molecular switches used for diverse purposes.…”

Molecular Switches and Motors Powered by Orthogonal Stimuli

“…[78] Chaur et al reported that an acylhydrazone 16 linked to aromatic pyrimidyl, pyridyl, and phenyl groups shows 1) thermally induced syn-anti conformational isomerism, 2) E-Z photoisomerization about the C=N bond, and 3) deprotonation-driven E-Z configurational change (Figure 15). [79] The Z-anti form (antiperiplanar conformation of the NH-CO bond) of 16 was detected by X-ray crystallographic analysis. However, NMR spectroscopic analysis indicated that Z-syn-16 predominates in solution at 298 K and that conformational switching to the Z-anti form occurs at lower temperature.…”

“…Light-, heat-, and pH-driven conformational/configurational switching of acylhydrazone 16. [79] merocyanine (MC) form, is another class of multimodal molecular switches. [80] Switching is triggered by light and other stimuli, such as heat, solvent exchange, metal ions, redox potential, pH change, and mechanical force, [42,81] and two distinct modes of structural change (ring opening/closing and E-Z isomerization around the central double bond in the MC form) can be controlled independently.…”