Effect of S–Se Bioisosteric Exchange on Affinity and Intrinsic Efficacy of Novel N-acylhydrazone Derivatives at the Adenosine A2A Receptor

In this work, we evaluated the conformational effect promoted by the isosteric exchange of sulfur by selenium in the heteroaromatic ring of new N-acylhydrazone (NAH) derivatives (3–8, 13, 14), analogues of the cardioactive compounds LASSBio-294 (1) and LASSBio-785 (2). NMR spectra analysis demonstrated a chemical shift variation of the iminic Csp2 of NAH S/Se-isosters, suggesting a stronger intramolecular chalcogen interaction for Se-derivatives. To investigate the pharmacological profile of these compounds at the adenosine A2A receptor (A2AR), we performed a previously validated functional binding assay. As expected for bioisosteres, the isosteric-S/Se replacement affected neither the affinity nor the intrinsic efficacy of our NAH derivatives (1–8). However, the N-methylated compounds (2, 6–8) presented a weak partial agonist profile at A2AR, contrary to the non-methylated counterparts (1, 3–5), which appeared as weak inverse agonists. Additionally, retroisosterism between aromatic rings of NAH on S/Se-isosters mimicked the effect of the N-methylation on intrinsic efficacy at A2AR, while meta-substitution in the phenyl ring of the acyl moiety did not. This study showed that the conformational effect of NAH-N-methylation and aromatic rings retroisosterism changed the intrinsic efficacy on A2AR, indicating the S/Se-chalcogen effect to drive the conformational behavior of this series of NAH.

A dramatic conformational effect of multifunctional zwitterions on zeolite crystallization

Carnitine functions as a mesoporogen in LTA zeolite synthesis whereas acetylcarnitine acts as a crystal growth modifier. Experimental and theoretical studies reveal a remarkable effect of molecular conformation on the roles of organic functional groups during zeolite crystallization.

Soluble Polyimides Bearing (cis, trans)-Hydrogenated Bisphenol A and (trans, trans)-Hydrogenated Bisphenol A Moieties: Synthesis, Properties and the Conformational Effect

In this work, hydrogenated bisphenol A (HBPA) based dinitro mixed isomers (1a′ and 1a) were synthesized and separated via vacuum distillation under the monitor of DSC and 1H NMR. Corresponding diamines (2a′ and 2a) were separately polycondensed with five commercial dianhydrides via a two-step thermal imidization to obtain PI-(1′-5′) and PI-(1-5). All the polyimides could afford flexible, tough, and transparent films, and most of them were readily soluble not only in common polar solvents like DMAc, but also in low boiling point solvents such as chloroform. 1H NMR spectra of the polyimides demonstrated that HBPA moiety showed no conformation changes during the preparation of polymers. For a given dianhydride, PI-(1-5) exhibited better thermal stability than that of PI-(1′-5′), this can be attributed that the equatorial, equatorial C–O in PI-(1-5) promoted denser and more regular molecular chain stacking, as can be evidenced by the WAXD and geometric optimization results. Additionally, when the dianhydride was ODPA, BPADA or 6FDA, no apparent difference was found in either the transmittance or solubility between two series of polyimides, which could be attributed that twisted and flexible ether linkages, as well as bulky substituents, led to the “already weakened” inter- and intramolecular CT interaction and cohesive force. However, when it came to rigid and stiff dianhydride, e.g., BPDA, PI-3′ took an obvious advantage over PI-3 in transmittance and solubility, which was possibly owed to the larger molecular chain d-spacing imparted by equatorial, axial C–O. An overall investigation of PI-(1′-5′) and PI-(1-5) on aspects of thermal, mechanical, morphological, soluble and optical performance values was carried out, and the conformation effects of HBPA isomers on the properties of two series of polyimides were discussed in detail.