Zn(II)-Coordination Complex(s) from Chiral Bisamides of L-Phenylalanine: Nanoscale-Based Biological Applications and Metallogelation.

Three 3-pyridyl-containing small organic bisamide molecules attached with innocent L-phenylalanine (PHE) side chain as building blocks and positional isomeric toluoyl terminals (PME, MME, and OME) have rationally been designed and synthesized for developing a new series of ZnII-coordination complexes. One of the unique molecular frameworks, having two hydrogen bond-equipped monodentate metal-coordinating sites and biologically potent chiral PHE moiety, was combined with ZnII halide salts under various conditions to produce the coordination complexes (CC1-CC7), thoroughly characterized by the single-crystal X-ray diffraction (SXRD) technique. Maintaining the similar component ratios of acquired CCs in 1:1 DMSO-water produced low-molecular weight metallogels (LMWGs) of PME/MME as envisaged from a rheology- and crystal engineering-based structural rationale. A structure-property correlation from the basis of PXRD of the bulk and xerogels and SXRD data of the isolated single crystals of reaction products clearly supports the crystal engineering-based design strategy based on which the metallogels are prepared. Hand-ground nanoscale ZnCl2-based coordination complex CC1 of PME was also studied for cytotoxicity (HEK-293 cell line) and anticancer activities (B16-F10 cell line) in the MTT assay.

Phenylalanine conjugated supramolecular hydrogels developed from the mafenide and flurbiprofen multidrug for biological applications.

A well-known nonsteroidal anti-inflammatory drug (NSAID), flurbiprofen (FLR), was first conjugated individually with two naturally occurring amino acids such as L-phenylalanine (PHE) and L-alanine (ALA). These covalent amidic bioconjugates were further reacted individually with mafenide (a drug for treating burn wounds) and amantadine (an antiviral drug) to develop primary ammonium monocarboxylate (PAM) salts. Interestingly, both the PHE-containing multidrug salts exhibited significant gelation ability with various solvents including biologically potent water or methyl salicylate (MS). The isolated hydrogel (HG) as well as all the organogels obtained from multidrug gelators were extensively characterized by dynamic rheology and rheoreversibility studies. The hydrogel of FLR·PHE·MAF and MS gels of FLR·PHE·AMN/FLR·AMN were also selectively characterized by table-top and FEG-TEM analyses. The temperature-dependent 1H-NMR spectroscopy of the selected HG further provided insights into the gelation mechanism and the only isolated single-crystal of the weakly diffracted gelator FLR·AMN also revealed the presence of 1D hydrogen-bonded networks. The pure hydrogelator FLR·PHE·MAF salt (which is also an ambidextrous gelator) was found to be promising in both mechanical (rheoreversible) and biological applications and was found to be effective in cytotoxicity, biocompatibility, anti-cancer activity (MTT and cell migration assay), antibacterial response (zone inhibition, turbidity, INT, and resazurin assay) and haemolysis studies.

Supramolecular Gels from Bis-amides of L-Phenylalanine: Synthesis, Structure and Material Applications.

A series of small organic molecules having a bis-amide backbone containing hydrogen-bond functionalities were rationally designed, synthesized and characterized to examine their ability to act as potential low-molecular-weight gelators (LMWGs). All the bis-amides were decorated with identical 3-pyridyl amide of L-phenylalanine moieties along with variously substituted terminal benzoyl groups. Gelation studies revealed that only 4-methylphenyl substituted bis-amide (PME) was capable of gelling both aqueous (DMSO/water) and methyl salicylate (MS) (an important solvent for topical formulation for medical applications) solvents; whereas 4-chlorophenyl and 4-bromophenyl substituted bis-amides (PCL, PBR, respectively) acted as organogelator for various organic solvents. On the contrary, 4-nitrophenyl as well as 3,5-dinitrophenyl substituted bis-amides (PNI, DNI, respectively) were unable to gel any solvents studied herein. The corresponding aqueous gel namely PME-HG and three methyl salicylate gels PME-MS, PCL-MS and PBR-MS were characterized by dynamic and table top rheology followed by electron microscopy. Single crystal X-ray diffraction (SXRD) data revealed crucial insights into the supramolecular assembly of all the gelator and nongelator bis-amides. Both PME-HG and PME-MS were rheoreversible - an important property in material applications. Interestingly, PME-MS displayed remarkable material properties such as shape-sustaining, loadbearing and self-healing. Selected MS and aqueous gels loaded with nano-molar iodine were found to possess anti-bacterial property as revealed by zone inhibition assay.

Anion Binding Studies of Urea and Thiourea Functionalized Molecular Clefts.

Two rationally designed 4-nitrophenyl-based molecular clefts functionalized with thiourea (L 1 ) and urea (L 2 ) have been synthesized and studied for a variety of anions by UV-Vis and colorimetric techniques in DMSO. Results from the binding studies suggest that both L 1 and L 2 bind halides showing the order: fluoride > chloride > bromide > iodide; and oxoanions showing the order: dihydrogen phosphate > hydrogen sulfate > nitrate > perchlorate. Each receptor has been shown to form a 1:1 complex with an anion via hydrogen bonding interactions, displaying distinct color change for fluoride and dihydrogen phosphate in solution. As compared to the urea-based receptor L 2 , the thiourea-based receptor L 1 exhibits stronger affinity for anions due the presence of more acidic thiourea functional groups.

A ratiometric fluorogenic probe for the real-time detection of SO32- in aqueous medium: application in a cellulose paper based device and potential to sense SO32- in mitochondria.

A new water soluble and fluorogenic probe (L) that can demonstrate a specific ratiometric detection of a SO2 derivative (SO32-) in 100% aqueous medium and live cells has been designed and synthesized. The detection process can be visualized by the naked eye, as the orange-red fluorescence of L turns into a strong blue fluorescence upon interaction with SO32-. L displayed several beneficial attributes such as detection in complete aqueous medium, extremely fast response time along with high selectivity and sensitivity. The ratiometric sensing was attributed to the selective nucleophilic addition reaction of SO32- with L. The probe was further used to develop a low cost microfluidic sensor device (µPAD). The probe was biocompatible and its potential to sense SO32- in mitochondria was captured in live HeLa cells.

Systematic size mediated trapping of anions of varied dimensionality within a dimeric capsular assembly of a flexible neutral bis-urea platform.

A rationally designed ortho-phenylenediamine based trifluoromethyl meta-disubstituted bis-urea receptor (L) exhibits effective, consistent and systematic binding in its neutral form towards smaller spherical halides (fluoride, chloride, bromide and iodide), and relatively larger planar carbonate and tetrahedral sulphate oxyanions. All the complexes are well characterized both in the solid-state and solution phase. In the presence of excess fluoride anions, the receptor L encapsulates a hydrated cyclic fluoride-water [F2(H2O)2]2- tetramer inside the n-TBA cation sealed dimeric complementary cavity (complex 1). Whereas excess n-TBA/TEA salts of chloride, bromide and iodide result in unusual (Cl-)2, (Br-)2, and (I-)2 doubly encapsulated 2 : 2 dimeric host-guest complexes (2a, 2b, 3 and 4). Two receptor units encapsulate a carbonate ion, via hydroxide induced aerial CO2 fixation (complex 5), and a sulphate anion (complex 6), respectively, in the presence of excess tetrabutylammonium hydroxide and bisulphate salt. 1H NMR titration and 2D NOESY experiments corroborate the solution-state binding and encapsulation of hydrated/non-hydrated halides and oxyanions via N-HA hydrogen bonding.

Fixation of atmospheric CO2 as novel carbonate-(water)2-carbonate cluster and entrapment of double sulfate within a linear tetrameric barrel of a neutral bis-urea scaffold.

A meta-phenylenediamine-based disubstituted bis-urea receptor L1 with electron-withdrawing 3-chloro and electron-donating 4-methylphenyl terminals has been established as a potential system to fix and efficiently capture atmospheric CO2 as air-stable entrapment of an unprecedented {CO32--(H2O)2-CO32-} cluster (complex 1a) within its tetrameric long straight pillar-like assembly entirely sealed by n-TBA cations via formation of a barrel-type architecture. L1 and its isomeric 4-bromo-3-methyl disubstituted bis-urea receptor L2 have been found to entrap similar kinds of water-free naked sulfate-sulfate double anion (complexes 1b and 2a) by cooperative binding of urea moieties inside the two pairs of the inversion-symmetric linear tetrameric barrel of L1 and L2, respectively. On the other hand, in the presence of excess halides, L1 self-assembles to form hexa-coordinated fluoride complex 1c and tetra-coordinated bromide complex 1d, while L2 self-assembles to form penta-coordinated fluoride complex 2b in the solid state via semicircular receptor architectures and non-cooperative H-bonding interactions of urea moieties.

An aggregation-induced emission (AIE) active probe for multiple targets: a fluorescent sensor for Zn(2+) and Al(3+) & a colorimetric sensor for Cu(2+) and F(-).

A rationally designed probe L, which consists of both cation and anion binding sites, is capable of displaying interesting aggregation induced emission (AIE) properties. L not only can sense Al(3+) and Zn(2+) through selective turn-on fluorescence responses in 9 : 1 methanol-HEPES buffer (5 mM, pH 7.3; 9 : 1, v/v) medium due to metal ion triggered AIE activity, but also can distinguish them through individual emission signals. L can also detect Cu(2+) in mixed buffer medium and F(-) in acetonitrile through sharp colorimetric responses. All the sensing processes are conspicuous through the naked eye. A theoretical study strongly backed the proposed sensing mechanisms.