Supramolecular Organogels Based on N-Benzyl, N′-Acylbispidinols

Abstract

The acylation of unsymmetrical N-benzylbispidinols in aromatic solvents without an external base led to the formation of supramolecular gels, which possess different thicknesses and degrees of stability depending on the substituents in para-positions of the benzylic group as well as on the nature of the acylating agent and of the solvent used. Structural features of the native gels as well as of their dried forms were studied by complementary techniques including Fourier-transform infrared (FTIR) and attenuated total reflection (ATR) spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and small-angle X-ray scattering and diffraction (SAXS). Structures of the key crystalline compounds were established by X-ray diffraction. An analysis of the obtained data allowed speculation on the crucial structural and condition factors that governed the gel formation. The most important factors were as follows: (i) absence of base, either external or internal; (ii) presence of HCl; (iii) presence of carbonyl and hydroxyl groups to allow hydrogen bonding; and (iv) presence of two (hetero)aromatic rings at both sides of the molecule. The hydrogen bonding involving amide carbonyl, hydroxyl at position 9, and, very probably, ammonium N-H+ and Cl− anion appears to be responsible for the formation of infinite molecular chains required for the first step of gel formation. Subsequent lateral cooperation of molecular chains into fibers occurred, presumably, due to the aromatic π−π-stacking interactions. Supercritical carbon dioxide drying of the organogels gave rise to aerogels with morphologies different from that of air-dried samples.

Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors

“… 34 This can be explained by a wide and diverse set of biological activities exhibited by compounds containing the bispidine framework. The key features of bispidines that allow their derivatives to be so widely used in medicinal chemistry and pharmacology are (1) their ability to selectively and independently functionalize at both nitrogen atoms; 35 (2) the ability to control the conformational behavior of the bicyclic core; 36 (3) and their pronounced complexing properties. 37 , 38 Bispidines have been studied as potential antagonists of serine proteases, including thrombin and factor Xa.…”

“…This can be explained by a wide and diverse set of biological activities exhibited by compounds containing the bispidine framework. The key features of bispidines that allow their derivatives to be so widely used in medicinal chemistry and pharmacology are (1) their ability to selectively and independently functionalize at both nitrogen atoms; (2) the ability to control the conformational behavior of the bicyclic core; (3) and their pronounced complexing properties. , Bispidines have been studied as potential antagonists of serine proteases, including thrombin and factor Xa. , There are also known studies of symmetrical bispidine derivatives working as inhibitors of Japanese encephalitis virus . However, in terms of application to the problems of combating coronavirus infections, in particular to the creation of inhibitors of the main viral protease, bispidines and their analogues have not yet been applied.…”

Reaction of β-Nitrostyrene with Diethyl Malonate in the Presence of Bispidines: The Unusual Role of the Organocatalyst

“…On the other hand, it can be assumed that primary betaine (Ad −+ ) cannot rapidly transform into a neutral adduct, since the NH + fragment is stabilized by the formation of hydrogen bonds not only with an adjacent nitrogen atom (which is well documented in the chemistry of bispidines [70][71][72][73]), but, highly likely, also with an oxygen atom of a closely located nitro group. In this case, betaine (Ad −+ ) may exist for a sufficient time to enable its carbanionic part to act as a strong base for the deprotonation of diethyl malonate.…”

Synthesis and Aminomethylation of 2-Amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile N-Methylmorpholinium Salt

“…3,7-Diazabicyclo[3.3.1]nonanes (bispidins) and related compounds are widely used as biologically active compounds [38,39], complexing agents for metals [40], radionuclides [41], as initial reagents for the synthesis of natural compounds [42], materials for imaging in positron emission tomography [43], platforms for chiral catalysts [44,45]. Recently, 3,7-diazabicyclononane derivatives have been successfully used as initial templates for constructing complex supramolecular assemblies [46][47][48][49]. Recently, submicromolar inhibitors of the main SARS-CoV-2 protease have been found among bispidins [50].…”