Enol-imine Form Research Articles

Square-planar nickel/copper(II) complexes of (E)-2-(((2-ethylphenyl)imino)(phenyl)methyl)phenol: Supramolecular analysis, keto-enol tautomerism, polymorphism and antibacterial activities

A new Schiff base proligand, (E)-2-(((2-ethylphenyl)imino)(phenyl)methyl)phenol (HL), was synthesized from 2-hydroxybenzophenone and 2-ethylaniline and its coordination chemistry with nickel(II) and copper(II) acetate explored. In solution, the proligand HL undergoes ketoimine-enolimine tautomerism which settles exclusively into an enolimine form in the solid-state. Interestingly, while a single crystalline habit was obtained for the nickel complex 1 (block-shaped single crystals), the copper species 2 was found to solidify in two detectable polymorphs: block-shaped crystals (2a, monoclinic space group P21/c) and rhombic crystals (2b, triclinic space group P-1). Single-crystal X-ray diffraction studies reveal that the N,O Schiff base ligand chelates the divalent metal ions with square-planar geometry in the isostructural 1 and 2a and in a distorted square-planar geometry with a dihedral chelate-plane angle of 27.9° in 2b. The copper complex 2 exhibits significant antibacterial activity against the E. coli and medium activity against S. aureus bacteria. The physical properties of the complexes were further probed using thermal techniques, while their electronic structure was investigated by electrochemistry and electronic absorption spectroscopy.

Experimental Studies of Schiff Base (E)-4-methoxy-2-(((2-phenoxyphenyl)imino)methyl) phenol Compound with Various Spectroscopic Methods

Schiff-based compounds, which represent an important class in the field of organic compounds, form the basis of this research article. This research article aims to investigate the synthesized compound (E)-4-methoxy-2-(((2-phenoxyphenyl) imino) methyl) phenol using experimental methods.FT-IR, UV-Vis, 13C and 1H Nuclear Magnetic Resonance (NMR) Spectroscopy and X-ray diffraction methods were used to elucidate the structural properties of the compound synthesized at the end of chemical processes. The structure solution was carried out from the data obtained as a result of X-ray analysis. According to these results, one of the two compounds in the asymmetric cell completed their formation in the enol-imine form and the other in the keto-amine form. This structural situation, which is rare in the literature, was supported and explained by FT-IR, 13C and 1H Nuclear Magnetic Resonance (NMR) spectroscopy studies.According to the results obtained as a result of UV-Vis spectroscopy, the structure revealed that the enol-imine form was dominant. The reasons for this situation were explained.

Free Energy Landscapes of the Tautomeric Interconversion of Pyridoxal 5'-Phosphate Aldimines at the Active Site of Ornithine Decarboxylase in Aqueous Media.

The pyridoxal 5'-phosphate (PLP) acts as a coenzyme for a large number of biochemical reactions. It exists in mainly two bound forms at the active site of the concerned enzyme: the internal aldimine, in which the PLP is bound with the ϵ-amino group of lysine at the active site, and the external aldimine, where the PLP is bound to the substrate amino acid. Both the internal and external aldimines have Schiff base linkage (N-H-O) and can exist in two tautomeric structures of ketoenamine and enolimine forms. In this work, we have investigated the free energy landscape for the tautomeric proton transfer in the internal and external aldimines at the active site of the ornithine decarboxylase enzyme in an aqueous medium. We performed hybrid quantum-classical metadynamics and force field-based molecular dynamics simulations, which revealed that the ketoenamine tautomer is more stable than the enolimine form. The QM/MM metadynamics calculations show that the free energy difference between the ketoenamine and enolimine forms for the internal aldimine is 3.9 kcal/mol, and it is found to be 5.8 kcal/mol for the external aldimine, with the ketoenamine form being more stable in both cases. The results are further supported by calculations of the binding free energies from classical simulations and static quantum chemical calculations in different environments. We have also analyzed the configurational structure of the microenvironment at the active site in order to have better insights into the interactions of the active site residues with the PLP in its two tautomeric forms.

Keto-enamine-based covalent organic framework with controllable anthraquinone moieties for superior H2O2 photosynthesis from O2 and water

Photocatalytic H2O2 production is a promising strategy for decentralized applications, but to realize efficient H2O2 production in the ambient conditions and absence of organic sacrifice remains challengeable. Herein, anthraquinone functionalized covalent organic frameworks (TpAQ-COFs) were fabricated by β-ketoenamines links of 2,6-diaminoanthraquinone (AQ) and 2, 4, 6-triformylphloroglucinol (Tp), and the structures and compositions were tuned by controlling the condensation time. The increase of time favors the assembly of TpAQ-COFs into more ordered lamellar stacking structure, and induces the increase of enol-imine form. The critical role of anthraquinone moieties as the active sites for oxygen reduction was proved, that is, facilitating charge separation and enhancing the activity and selectivity of H2O2 production. Upon visible light irradiation, the TpAQ-COF synthesized after 12 h reaction has the highest content of anthraquinone moieties and the best performance for H2O2 production (420 μmol h−1 g−1) in the absence of organic sacrificial agents. These findings bring insights to incorporate anthraquinone chemistry into photocatalysts at molecular levels for efficient H2O2 production.

Two new Schiff bases of (E)-2,4-di-tert-butyl-6-((4-fluorophenylimino)methyl)phenol (I) and (E)-2,4-di-tert-butyl-6-((3-iodo-4-methylphenylimino)methyl)phenol (II): structural, spectroscopic and quantum chemical calculations

In this study, two Schiff bases, (E)-2,4-di-tert-butyl-6-((4-fluorophenylimino)methyl)phenol (I) and (E)-2,4-di-tert-butyl-6-((3-iodo-4-methylphenylimino)methyl)phenol (II) are synthesized and characterized by XRD, FT-IR, UV-Vis and NMR techniques. (I) and (II) compounds display enol-imine form by O-H···N intramolecular hydrogen bonds. The title compounds are stabilized by C—H···π interactions. The presence of various inter molecular interactions and 2D-fingerprint regions are well supported by the Hirshfeld surface analysis. Also experimental optical energy band and gap studies are discussed. All chemical theoretical computations are calculated by Density Functional Theory (DFT) at B3LYP level by using 3-21 G basis set. Chemical activity analyses are showed that compounds have large energy gaps, higher values of hardness and lower values of softness support the title molecules are high kinetic stability. Also, chemical activity properties generate foresight about electrophilic and nucleophilic nature.

Interaction of Copper(II) Complexes of Bidentate Benzaldehyde Nicotinic Acid Hydrazones with BSA: Spectrofluorimetric and Molecular Docking Approach.

Two copper(II) complexes of 4-chloro- and 4-dimethylaminobenzaldehyde nicotinic acid hydrazones were prepared and characterized by elemental analysis, mass spectrometry, infrared and electron spectroscopy and conductometry. These rare examples of bis(hydrazonato)copper(II) complexes are neutral complex species with copper(II) center coordinated with two monoanionic bidentate O,N-donor hydrazone ligands coordinated in enol-imine form. The interaction of hydrazone ligands and corresponding copper(II) complexes with CT DNA and BSA was investigated. Copper(II) complexes are slightly effective in binding the DNA than pristine hydrazones. The results indicate groove binding or moderate intercalation which are not significantly affected by the nature of substituent at hydrazone ligands. On contrary, affinities of two copper(II) complexes toward BSA significantly differs and depends on the nature of the substituent, however in absence of thermodynamic data difference in nature of binding forces cannot be excluded. The complex bearing electron-withdrawing 4-chloro substituent has larger affinity toward BSA compared to 4-dimethyamino analogue. These findings were theoretically supported by molecular docking study.

Fluorescent core-shell SiO2@vertical covalent organic frameworks nanosheets for sensing application

Fluorescent covalent organic frameworks (COFs) are attracting more and more attentions. However, it is very difficult to obtain COFs with strong fluorescence due to fluorescence quenching caused by interlaminar accumulation and intramolecular rotation. Here, the core-shell SiO2@COFTFP-TAPB (1,3,5-tri(4-aminophenyl)-benzene: TAPB, 1,3,5-triformylphloroglucinol: TFP) was prepared by assembling vertical COFTFP-TAPB through amine-aldehyde dehydration condensation reaction on -NH2-SiO2 nanospheres (NPs) for the first time. The 2D COFTFP-TAPB nanosheets with thickness of 25 nm and good crystallinity vertically stand on the surface of -NH2-SiO2 NPs based on the imine-linkage. Such core-shell structure results in larger BET surface area, effectively overcomes the interlaminar accumulation, and improves optical properties of COFTFP-TAPB. The core-shell SiO2@COFTFP-TAPB exhibits multiemission from the enol-imine form and keto-enamine form, which is sensitive to pH. After loading with glucose oxidase and urease, it could be used to detect glucose and urea successfully. The detection ranges are 0.23 μM-14 mM and 1.50 μM-90 mM, and the detection limits reaches 0.07 μM and 5.14 μM, respectively. The work provides a feasible idea to overcome the interlaminar accumulation and reaggregation of COFs during application.

Iron(III) Complexes Derived From Azo-Containing Salicylaldoxime Ligands: Synthesis, Structures and Biological Evaluations

Two novel mononuclear Fe(III) complexes derived from azo-containing salicylaldoxime ligands were synthesized and characterized by elemental analyses, spectroscopic data i.e. IR, 1H NMR, UV-Vis, electrospray ionization mass spectra, molar conductivity, and magnetic susceptibility measurements. Both the experimental and theoretical results strongly suggest that the ligands have a major contribution to the azo enol imine form instead of the hydrazo keto imine and azo keto amine forms in solution/solid-state. The electronic spectra of the ligands and their iron(III) complexes were calculated theoretically for the band assignments by using DFT and TD-DFT/CPCM methods. DNA binding, cleavage, and antioxidative activities of the investigated compounds were studied. It has been shown that the ligands and their iron (III) complexes tested bind to DNA via the intercalative mode. One of the most striking results among the antioxidant activity tests is that the hydroxyl radical scavenging activities of the ligands and complexes are higher than the standard antioxidant mannitol.

Novel sterically demanding Schiff base dyes: An insight from experimental and theoretical calculations

We report extensive experimental and theoretical studies on structural and photophysical properties of two new bulky Schiff base dyes 1 and 2, obtained from the reaction of cyclohexylamine with the 5-bromosalicylaldehyde or 2-hydroxy-1-naphthaldehyde. The structure of 1 exhibits the enol-imine form in the solid state and is characterized by a typical intramolecular O–H⋯N hydrogen bond. Contrarily, the structure of 2 was found to be in the cis-keto-enamine tautomer, stabilized by an intramolecular N–H⋯O hydrogen bond. Favoured intermolecular H⋯H, H⋯C, H⋯O and H⋯Br contacts in the structure of 1 and H⋯H, H⋯C and H⋯O in the structure of 2 are responsible for the overall crystal packing of the dyes. The UV–vis spectra of 1 in cyclohexane, THF, CH2Cl2 and CH3CN exhibit bands in the UV region, indicating the enol-imine form, while in MeOH the UV–vis spectrum of 1 exhibits an additional band in the visible region at 410 nm, which corresponds to the cis-keto-enamine tautomer. The absorption spectra of 2 in the same solvents, except cyclohexane, also contain a band in the visible region up to about 450 nm. This band exhibits two maxima, which can be assigned to an equilibrium between the cis-keto-enamine and zwitterion forms, of which the latter one is structurally the same as the former isomer. The UV–vis spectrum of 2 in cyclohexane reveals only traces of the cis-keto-enamine. The dye 1 was found to be emissive exclusively in MeOH, while 2 is emissive in all the studied solvents, of which the most pronounced and the most negligible emission was found for MeOH and cyclohexane, respectively. An intense emission band in the spectrum of 1 at 468 nm arises from the emission of two conformers of the cis-keto-enamine* form. The solution of 2 in MeOH showed dual emission with the bands centered at 346 and about 450 nm, of which the latter one is a superposition of two single bands. The two low-energy emission bands arise from the emission of the cis-keto-enamine* and zwitterion* forms, while the high-energy emission band most likely corresponds to the naphthalene fragment. Finally, π-resonanse stabilization (RAHB) effect is found to be crucial for tuning the tautomerization mechanism through the alteration of intramolecular O–H⋯N hydrogen bond.

A Family of Ethyl N-Salicylideneglycinate Dyes Stabilized by Intramolecular Hydrogen Bonding: Photophysical Properties and Computational Study.

In this work we report solvatochromic and luminescent properties of ethyl N-salicylideneglycinate (1), ethyl N-(5-methoxysalicylidene)glycinate (2), ethyl N-(5-bromosalicylidene)glycinate (3), and ethyl N-(5-nitrosalicylidene)glycinate (4) dyes. 1–4 correspond to a class of N-salicylidene aniline derivatives, whose photophysical properties are dictated by the intramolecular proton transfer between the OH-function and the imine N-atom, affording tautomerization between the enol-imine and keto-enamine forms. Photophysical properties of 1–4 were studied in different pure non-polar and (a)protic polar solvents as well as upon gradual addition of NEt3, NaOH, and CH3SO3H. The DFT calculations were performed to verify the structures of 1–4 as well as their electronic and optical properties.

Experimental (XRD, FTIR, UV–Vis, NMR) and theoretical investigations (chemical activity descriptors, NBO, DNA/ECT) of (E)-2-((2-hydroxy-5-methoxybenzylidene)amino)-4-nitrophenol

The new Schiff base of compound was synthesized and characterized by XRD, FTIR, UV–Vis and NMR techniques. The structure with two molecules in its asymmetric unit showed the enol-imine form in one and the keto-amine form in the other. Both tautomeric forms are stabilized by strong O–H…N and N–H…O intramolecular hydrogen bonds. Optimized geometrical parameters and calculated spectroscopic features obtained by DFT/B3LYP/6-31G(d,p) calculations show a good agreement with the experimental data. Accordingly local and global chemical activity descriptors were investigated.

Tautomerism in carbohydrate-derived salicylidene schiff bases: Solution, solid-state, and theoretical investigations

Enol-imine and keto-amine tautomerism in a series of carbohydrate-derived Schiff bases were investigated in gas, liquid, and solid-state by theoretical calculation, NMR spectroscopies, and single-crystal XRD, respectively. Two of these sugar-modified Schiff-bases derived from benzyl 2-deoxy-2-salicylideneamino-α-D-glucopyranoside (H2L3-tBu and H2L3-OMe) were synthesized and crystallized from methanol and their crystal structures determined. The results show that H2L3-tBu crystallizes in the enol-imine form while H2L3-OMe adopts the keto-amine form. The crystal packing of the latter is characterized by hydrogen bonding via the co-crystallized methanol molecules. Calculations were performed to shed light as to what parameters govern these behaviors. In this regard, eight different salicylideneamino substituted sugar-modified Schiff-bases (considering electronic and steric effects) were studied theoretically. Separate calculations were performed both in the gas phase as well as in methanol as solvent. It was found that the enol-amine form of the Schiff base is the stable tautomer in the gas phase. The electronic of the substituents was also seen to influence this tendency as electron releasing groups were found to increase the energy difference between keto and enol forms. In contrast the opposite trends are seen for electron-withdrawing groups in both gas phase and solution. Moreover, these energy differences between both tautomers in methanol are considerably lower than those obtained in the gas phase. Molecular structures of selected Schiff bases in solution were also studied experimentally by utilization of variable temperature (VT) 1H NMR and low temperature 1H−1H COSY. The results indicate that the presence of the other tautomer can be confirmed at lower temperatures. Based on these findings, it is believed that the participation of methanol in the stabilization of tautomers is influenced by both the position and nature of the substitution.

Photophysical properties of ethyl N-(5-bromosalicylidene)glycinate and ethyl N-(5-nitrosalicylidene)glycinate in CH2Cl2

In this work, we report photophysical studies of two Schiff bases, namely ethyl N-(5-bromosalicylidene)glycinate (1) and ethyl N-(5-nitrosalicylidene)glycinate (2). Both dyes were synthesized from the ethyl ester of glycine hydrochloride and corresponding salicyladehyde derivatives in the presence of trimethylamine using a newly developed sonochemical approach in the ethanol medium, which allowed to completely avoid using benzene as a reaction medium. The UV–vis spectrum of 2 in CH2Cl2 is described by the presence of the corresponding absorption band in the visible region, characteristic for the cis-keto-enamine tautomer as opposed to the enol-imine form prevalent in the spectrum of 1 in the same solvent. Both 1 and 2 found to be inert to the presence of NEt3, regardless of its concentration, in CH2Cl2. During the titration of a solution of 1 in CH2Cl2 by CH3SO3H a new band in the visible region appears and gradually increases, which is due to a specific interaction of 1 with CH3SO3H, where the solute molecules are not protonated but, contrarily, the keto-enamine tautomer is formed. This also results in an emission band at about 475 nm, which is gradually increased with increasing of the acid concentration. The emission band arises from the emission of the keto-enamine tautomer of 1, exhibiting, most likely, two conformers. Contrarily, gradual addition of CH3SO3H into a solution of 2 in CH2Cl2 decreases an intensity of the band in the visible region, characteristic for the cis-keto-enamine tautomer, until it completely disappears. While the bands at 239 and 318 nm decrease upon addition of CH3SO3H, a shoulder at about 260 nm increases up to 2 eqv. of the added CH3SO3H, followed by decreasisng until it completely disappears. This is due to protonation of the imine nitrogen atom, followed by the protonation of the NO2 group. Titration of a solution of 2 in CH2Cl2 by CH3SO3H increases intensity of the emission band up to about 2 eqv. of the added acid, followed by decreasing of this band. The resulting emission band arises from the emission of the enol-imine* and cis-keto-enamine* forms.

Coordination properties of two new Schiff-base phenoxy-carboxylates and comparative study of their antioxidant activities

Two novel tridentate Schiff-base ligands containing carboxylate groups were obtained from the condensation of 3-amino-4-hydroxybenzoic acid with either acetylacetone (H3L1) or salicylaldehyde (H3L2). H3L1 reacted with copper(II) acetate and pyridine (strongly coordinating solvent) to afford the C1 complex, while reaction of H3L2 with nickel(II) acetate and pyridine afforded two types of complexes C2 and C3. The two ligands and their metal complexes were fully characterized by elemental analysis, XRD and spectroscopic analysis. Upon its fully deprotonated state, (L1)3− coordinates in a keto-enamine fashion and acts as a ditopic binder through an ONO tridentate donor system and an O monodentate donor system (carboxylate). Upon its doubly deprotonated state, (HL2)2− ligand acts either as monotopic tridentate binder (i.e. enol-imine form with an ONO donor system that lead to complex C2) or as a ditopic ligand (ONO tridentate and O monodentate donor systems to afford complex C3). The molecular structure of all the compounds were determined by single crystal X-ray diffraction studies and revealed several important characteristics. In complex C1, the Cu(II) cations are five-coordinated with a slightly distorted square pyramidal geometry, while in C2 and C3 complexes, the Ni(II) ions are four and six–coordinated with a square planar and a slightly distorted octahedral geometry, respectively. Following this structural investigation, the antioxidant activities of the free ligands and their metal complexes were then investigated and demonstrated interesting antioxidant features especially for H3L2 and complex C3. Lastly, temperature dependent magnetic susceptibility measurements showed the presence of ferromagnetic interactions in C1 mediated through the phenoxido bridges.

Prototropic Tautomerism of Salicylideneimines. Crystal Structure of 3,5-Dichlorosalicylideneallylimine

Azomethine, derived from 3,5-dichlorosalicylaldehyde and allylamine, was synthesized and studied by X-ray diffraction. The compound exists in the enol-imine tautomeric form (the hydrogen atom is located on the oxygen atom). The structure is stabilized by the intramolecular О(1)–Н(1А)···N(1) hydrogen bond (О–Н, 0.82 A; H···N, 1.91 A; O···N, 2.580 A; О–H–N, 138°).

Biomimetic systems trigger a benzothiazole based molecular switch to 'turn on' fluorescence.

Molecular switches are valuable tools for the detection of many chemical and biological processes. On the other hand, Schiff bases are known for their simplicity in synthesis and their enormous biochemical applications. In this scenario, when a strategically designed Schiff base acts as a molecular switch in biomimetic environments drags inevitable attention. In this article, we hereby demonstrate an interesting behavior of a strategically designed bioactive benzothiazole based Schiff base (E)-2-(((6-chlorobenzo[d]thiazol-2-ylimino)methyl)-5-diethylamino) phenol (CBMDP) whose fluorescence characteristics dramatically modulate as consequence of its structural modification in aqueous and biomimetic environments individually. Electronic absorption, steady state and time resolved fluorescence spectroscopic techniques along with DFT based quantum chemical calculation evidence that in pure organic solvents CBMDP exists in highly fluorescent enol-imine (N) form which transform into feebly fluorescent hydrated species (H) in bulk aqueous media. Contrariwise, on interaction with the ionic and non-ionic micellar media or with liposome, a structural restoration occurs from less fluorescent hydrated (H) species into a highly fluorescent normal (N) one. This molecular flipping of the title compound upon micellar compartmentalization is possibly caused by the micropolarity of the local environment and further supported by its spectral behavior in different polarity gradient solvent mixture of water-dioxane (protic-aprotic) and water-methanol (protic -protic). Usually, Schiff bases are prone to hydrolysis in aqueous media, interestingly, the structural framework of this strategically designed molecule only allow the first step of hydrolysis, which is hydration of azomethine linkage whereas it withstand the second step, and that possibly helps the structural restoration process. Hence the article described herein may emphasize how a systematically designed Schiff base framework can be used as 'turn off- turn on' fluorescent molecular switch which may be extremely useful for its applications in the area of biochemical sensors.

Structure investigations of Schiff bases derived from 3-amino-1H-1,2,4-triazole

In the present paper, twelve Schiff bases derived from 3-amino-1H-1,2,4-triazole (ATz) and various benzaldehydes, and salicylaldehydes were synthesized. The 1H, 13C, and 15N NMR data are discussed in relation to the structure of ATz and its imine products. In addition, X-ray, ATR-FTIR, and UV–Vis analytical techniques are used for structure elucidation of ATz-based Schiff bases. It was found that the starting material, 3-amino-1H-1,2,4-triazole, exists as tautomeric mixture of three forms (Graphical Abstract) in solution, whereas in the solid state (13C and 15N CPMAS data) potentially tautomeric proton is located on nitrogen atom traditionally marked as N-2 (Graphical Abstract, 2NH structure). All investigated Schiff bases derived from salicylaldehydes exist in both phases as tautomeric equilibrium mixtures, where enol-imine forms are dominated structures. The positions of those equilibria only very slightly depend on substituents in phenol ring. Generally, the contributions of keto-amine forms in the solid state are higher comparing with DMSO solutions.

Synthesis, Crystal Structure, Anion Sensing Applications and DFT Studies of (E)-2-[(3,5-Bis(trifluoromethyl)phenylimino)methyl]-4-chlorophenol

We report the synthesis and characterization, colorimetric anion sensors properties, density functional theory (DFT) calculation studies of a Schiff base (E)-2-[(3,5-bis(trifluoromethyl)phenylimino)methyl]-4-chlorophenol. The molecular structure of the title compound was experimentally determined using X-ray single-crystal data and was compared to the structure predicted by theoretical calculations using DFT. The experimental and calculated data (using DFT) of the title compound have been compared. To investigate the tautomeric stability, some properties such as total energy, HOMO and LUMO energies, the chemical hardness (η), the ionization potential, the electron affinity, the absolute electronegativity (χ), the absolute softness (σ) of the compound were obtained at B3LYP/6–311++G(d,p) level in the gas phase and solvent phase. The calculated results showed that the enol-imine form of the compound was more favorite than keto-amine form. The colorimetric response of the Schiff base receptors in DMSO was investigated.

Exploration of the ESIPT process in a newly designed potential bioactive thiosemicarbazone Schiff base: Spectroscopic analysis accompanied by molecular optimization and crystallographic study

The DNA targeting nature of thiosemicarbazone based Schiff bases has provided a great platform for synthesis of its novel derivatives and their progressive exploitation as therapeutic agents. The present work embodies the synthesis of a potential bioactive pharmacophore thiosemicarbazone Schiff base derivative viz. (E)-1-(4-(diethylamino)-2-hydroxybenzylidene)-4,4-dimethyl-thiosemicarbazide (DAHTS) along with its structural characterisation by 1H NMR, FT-IR, mass spectrometry and single crystal X-ray diffraction analysis. Identification of ground and excited state geometries of the synthesized DAHTS molecule, with possibility of solvent dependent excited state intramolecular proton transfer (ESIPT) reaction have also been unveiled using electronic absorption, steady state and time resolve fluorescence spectroscopic techniques. The ESIPT process has further been validated by Density functional theory (DFT) and Time-dependent density functional theory (TD-DFT) based quantum chemical calculations. Spectral and single crystal XRD analysis indicate existence of intramolecular H-bonding between phenolic hydrogen and azomethine nitrogen in DAHTS molecule that stabilises the normal enol-imine (E) form in the ground state of DAHTS molecule. The synthesised molecule exhibits dual emission in non-polar hexane. On photoexcitation, DAHTS possibly undergoes excited state intramolecular proton transfer (ESIPT) reaction to produce keto-amine species (K) in nonpolar solvents. Frontier molecular orbital (FMO) analysis indicates that although intramolecular proton transfer reaction possibly might not occur in ground state of DAHTS but it may become feasible in the lowest singlet excited state of enol-imine form (E*) to produce its excited tautomer (K*). The lower energy difference (1.17 kcal/mol) between excited enol-imine (E*) and keto-amine (K*)form, obtained from Potential energy curve (PEC) corroborates the observed dual emission of the synthesised fluorophore. DFT and TD-DFT studies also aid in visualization of electronic charge displacement inside the molecular framework of DAHTS; which in turn suggests partial increase of Mulliken charge of azomethine nitrogen that further makes way for intramolecular proton transfer in the excited state. The amalgamated spectroscopic and theoretical research described herein, delivers enormous information about comprehensive synthetic and photophysical aspects of potential bioactive thiosemicarbazone derivatives for further utilization in medicinal chemistry research.

Free energy landscapes of prototropic tautomerism in pyridoxal 5'-phosphate schiff bases at the active site of an enzyme in aqueous medium.

We have performed hybrid quantum-classical metadynamics simulations and quantum chemical calculations to investigate the free energy landscapes of intramolecular proton transfer and associated tautomeric equilibrium in pyridoxal 5 '-phosphate (PLP) Schiff Bases, namely the internal and external aldimines, at the active site of serine hydroxymethyltransferase (SHMT) enzyme in aqueous medium. It is important to determine the relative stability of the two tautomers (ketoenamine and enolimine) of the PLP aldimines to study the catalytic activity of the concerned enzyme. Both the internal PLP aldimine (PLP-LYS) and the external PLP aldimine (PLP-SER) of SHMT are found to have a higher stability for the ketoenamine tautomer over the enolimine form. The higher stability of the ketoenamine tautomer can be attributed to the more number of favorable interactions of the ketoenamine form with its surroundings at the active site of the enzyme. The ketoenamine is found to be stabilized by about 2.5 kcal/mol in the PLP-LYS internal aldimine, while this stabilization is about 6.7 kcal/mol for the PLP-SER external aldimine at the active site of the enzyme compared to the corresponding enolimine forms. The interactions faced by the PLP aldimines at the active site pocket determine the relative dominance of the tautomers and could possibly alter the tautomeric shift in different PLP dependent enzymes. © 2018 Wiley Periodicals, Inc.