Schiff Base Analogues Research Articles

Antibacterial and cytotoxic activities of Schiff base analogues of 4-aminoantipyrine

Schiff base is the class of compounds showing wide range of biological activities having the azomethine (-N=CH-) active pharmacophore, which play major roles in their significant bio-activities. A series of Schiff base analogues of 4-aminoantipyrine analogues have been tested for bactericidal and cytotoxic activities against selected bacterial strains and brine shrimp (Artemia salina) nauplii, respectively. Of the compounds tested, two compounds showed a good inhibition of bacterial growth against E. coli and C. sakazakii, whereas three compounds demonstrated high cytotoxicity with LC50 values of 225, 480, and 581 ppm, in a short term bioassay using A. salina. Qualitative structure-cytotoxic activity relationships were studied using physicochemical parameters; a good correlation between clogP and cytotoxic activity was observed.

Evidence for catalytic water oxidation by a dimanganese tetrakis-Schiff base macrocycle

A dimanganese tetrakis-Schiff base complex [MnII2L]2+, where L provides a N6O2 coordination environment, has been synthesized and characterized via electrochemical and spectroscopic studies. Cyclic voltammograms (CV) of [MnII2L]2+ in propylene carbonate, to which water has been added as a limiting reagent, show an increase in current starting at +1.3V versus Fc+/0. The current shows a first order dependence on H2O and [MnII2L]2+, indicative of electrocatalytic water oxidation. Controlled potential electrolysis produced O2 in 39–45% Faradaic efficiency. Blocking the axial coordination site to the manganese centers by a μ-carboxylato axial ligand in an analogous Schiff base complex [MnII2LAc]+ lowers the catalytic activity, suggesting the importance of an open coordination site to the central manganese atoms for aqua ligands. Photosensitization of [MnII2L]2+ with [Ru(bpy)3]2+ and K2S2O8 in acetonitrile–water mixtures produced O2 as measured by a Clark electrode, with the rate of O2 evolution proportional to [MnII2L]2+.

Phenol–Quinone Tautomerism in (Arylazo)naphthols and the Analogous Schiff Bases: Benchmark Calculations

Tautomerization energies of a series of isomeric [(4-R-phenyl)azo]naphthols and the analogous Schiff bases (R = N(CH3)2, OCH3, H, CN, NO2) are calculated by LPNO-CEPA/1-CBS using the def2-TZVPP and def2-QZVPP basis sets for extrapolation. The performance of various density functionals (B3LYP, M06-2X, PW6B95, B2PLYP, mPW2PLYP, PWPB95) as well as MP2 and SCS-MP2 is evaluated against these results. M06-2X and SCS-MP2 yield results close to the LPNO-CEPA/1-CBS values. Solvent effects (CCl4, CHCl3, CH3CN, and CH3OH) are treated by a variety of bulk solvation models (SM8, IEFPCM, COSMO, PBF, and SMD) as well as explicit solvation (Monte Carlo free energy perturbation using the OPLSAA force field).

Fluorescence ‘turn-on’ sensor for F− derived from vitamin B6 cofactor

A novel vitamin B6 Schiff base analog (L) was synthesized by combining vitamin B6 cofactor pyridoxal with 2-aminophenol. Receptor L displays a color change detectable by the naked-eye from yellow to red in the presence of fluoride and acetate due to the formation of hydrogen bonding host-guest complexes in 1 : 1 stoichiometry. Importantly, receptor L showed fluoride-selective 'turn-on' fluorescent response with a detection limit (3σ) of 7.39 × 10(-8) M.

Synthesis of novel Schiff base analogues of 4-amino-1,5-dimethyl-2-phenylpyrazol-3-one and their evaluation for antioxidant and anti-inflammatory activity

4-Aminoantipyrine (4-amino-1,5-dimethyl-2-phenylpyrazole-3-one) and its analogues have been found to be compounds of interest for their anti-inflammatory, analgesic, antiviral, antipyretic, antirheumatic and antimicrobial activities. In the present study, Schiff base analogues of 4-aminoantipyrine were synthesized by the condensation reaction with substituted benzaldehydes and then evaluated for their antioxidant and anti-inflammatory activities. From among the synthesized compounds (3a–m, 4 and 5), 3k and 3f exhibited the highest antioxidant activity followed by 3g, 3l, 3c, 3i, 5, 3m and 3h. The IC50 values for compounds 3k and 3f were found to be 0.44 and 0.93μM, respectively, comparable to that of ascorbic acid (IC50 0.41μM), a standard antioxidant agent. From the comparisons between the hydroxylated and methoxylated compounds, the rank order of antioxidant activity for the products resulting from benzylidene phenyl ring substitution was 2,4,6-OH>3,4-OH>3-OMe-4-OH>3,5-OMe-4-OH>2,4-OH>3-Me-4-OMe>3,4-OMe>4-OMe>4-OH. The structure–activity relationship study revealed that the position and nature of the substituted group on the benzylidene phenyl ring of the Schiff base analogues of 4-aminoantipyrine play an important role in their antioxidant activity. The anti-inflammatory activity of 3f, which also exhibited excellent antioxidant activity, was evaluated in terms of its inhibition of NO production, an inflammatory modulator, in LPS pretreated RAW 264.7 cells using the Griess method. We also examined whether or not this compound had effect on iNOS and COX-2 mRNA expression in RAW 264.7 cells. It was observed that compound 3f significantly reduced NO production and inhibited LPS-stimulated iNOS and COX-2 mRNA levels in a dose-dependent manner. Overall, 3f showed promising antioxidant and anti-inflammatory activities and may be used as the lead compound in a future study.

Double-pillared cobalt Pacman complexes: synthesis, structures and oxygen reduction catalysis

The syntheses and structures of binuclear cobalt complexes of a double-pillared cofacial Schiff-base pyrrole macrocycle (L) were determined and their activity as catalysts for the oxygen reduction reaction evaluated. The new binuclear cobalt complex, [Co(2)(L)], 1 was formed in good yield using a salt-elimination method and was characterised as adopting a cofacial structure in solution by NMR spectroscopy and as its THF and pyridine solvates in the solid state by X-ray crystallography. Using a variety of spectroscopic techniques, this complex was found to react reversibly with dioxygen to form a new paramagnetic complex. Furthermore, the new aqua-hydroxy double salt [Co(2)(μ-H(3)O(2))(py)(2)(L)][BF(4)] 2 was characterised by X-ray crystallography. In acidified benzonitrile solution, 1 behaves as a catalyst for the selective four-electron reduction of dioxygen to water and showed a large improvement in efficacy compared to its o-phenylene Schiff-base analogues.

Functionalization of mesoporous silica membrane with a Schiff base fluorophore for Cu(II) ion sensing

A Schiff base (SB) immobilized hybrid mesoporous silica membrane (SB-HMM) was prepared by immobilizing a Schiff base onto the pore surface of mesoporous silica (pore size = 3.1 nm) embedded in the pores of a porous anodic alumina membrane. In contrast to the non-fluorescent analogous SB molecule in homogeneous solutions, SB-HMM exhibited intense fluorescence due to emission enhancement caused by aggregation of SB groups on the pore surface. The high quantum efficiency of the surface SB groups allows SB-HMM to function as a fluorescent sensor for Cu(II) ions in an aqueous solution with good sensitivity, selectivity and reproducibility. Under the optimal conditions described, the linear ranges of fluorescence intensity for Cu(II) are 1.2–13.8 (M ( R 2 = 0.993) and 19.4–60 ( R 2 = 0.992) (M. The limit of detection for Cu(II) is 0.8 μM on basis of the definition by IUPAC ( C LOD = 3.3 S b/ m).

Synthesis, characterization and urease inhibitory activity of oxovanadium(V) complexes with similar Schiff bases

A series of structurally similar oxovanadium(V) complexes with analogous Schiff bases have been prepared and structurally characterized. The urease inhibitory activities of the complexes were investigated. The shorter the terminal groups of the Schiff base ligands are, the stronger the urease inhibitory activities of the oxovanadium(V) complexes. A series of structurally similar oxovanadium(V) complexes with analogous Schiff bases have been prepared and structurally characterized. The urease inhibitory activities of the complexes were investigated. ► A series of oxovanadium(V) complexes with Schiff bases have been synthesized. ► The complexes have been characterized by elemental analyses, IR spectra, and single crystal X-ray diffraction. ► The complexes show from moderate to strong urease inhibitory activity. ► The molecular docking study of the complexes with urease was performed.

Solid State NMR Spectroscopy as a Precise Tool for Assigning the Tautomeric Form and Proton Position in the Intramolecular Bridges of o-Hydroxy Schiff Bases

Two analogous Schiff bases, (S,E)-2-((1-hydroxy-3-methyl-1,1-diphenylbutan-2-ylimino)methyl)phenol (1) and (S,Z)-2-hydroxy-6-((1-hydroxy-3-methyl-1,1-diphenylbutan-2-ylamino)methylene)cyclohexa-2,4-dienone (2), exist in the solid state as phenol-imine and keto-amine tautomers, respectively. Their crystal structures were solved using the X-ray diffraction method. Sample 1 forms orthorhombic crystals of space group P2(1)2(1)2(1), while 2 forms monoclinic crystals of space group P2(1). In each sample, one molecule is in the asymmetric unit of the crystal structure. One-dimensional and two-dimensional solid state NMR techniques were used for structure assignment and for inspection of the (13)C and (15)N δ(ii) of the chemical shift tensor (CST) values. NMR study indicates that the span (Ω = δ(11)-δ(33)) and the skew (κ = 3(δ(22)-δ(iso)/Ω) are extremely sensitive to change in the tautomeric form of the Schiff bases. Theoretical calculations of NMR shielding parameters for 1 and 2 and a model compound with reduced aliphatic residue were performed using the GIAO method with B3LYP functional and 6-311++g(d,p) basis sets. From comparative analysis of the experimental and theoretical parameters, it was concluded that the position of hydrogen in the intramolecular bridge has tremendous influence on (13)C and (15)N CST parameters. Inspection of Ω and κ parameters allowed for the establishment of the nature of the hydrogen bonding and the assignment of the equilibrium proton position in the intramolecular bridges in the solid state.

Diastereoselective Assembly of Helicates Incorporating a Hexadentate Chiral Scaffold

AbstractThe condensation of enantiopure (1R,2R)‐(–)‐1,2‐diaminocyclohexane with two equivalents of 2,2′‐bipyridine‐6‐carbaldehyde followed by reduction with NaBH4 allows the facile synthesis of the enantiopure hexadentate ligand (R,R)‐3. Each tridentate metal‐binding domain in (R,R)‐3 exhibits a degree of flexibility arising from inversion at the amine nitrogen centre and rotation about N–C and C–C single bonds. This leads to the formation of either M‐[M{(R,R)‐3}]2+ or P‐[M{(R,R)‐3}]2+. The solid‐state structures of the copper(II), iron(II) and zinc(II) complexes of (R,R)‐3 all show a preference for M‐[M{(R,R)‐3}]2+. In solution, [Fe{(R,R)‐3}]2+ exists predominantly as one diastereoisomer (assumed to be the M‐form). The preference for the M‐ over P‐form is rationalized in terms of a favourable anti configuration of the NH and cyclohexane‐1,2‐diyl CH hydrogen atoms in the M‐form, and an unfavourable syn‐configuration in the P‐form. When (R,R)‐4, the Schiff base analogue of (R,R)‐3, combines with zinc(II) or silver(I), [2+2] double helicates with M‐chirality assemble in the solid state. With (S,S)‐4, iron(II) also assembles into a dinuclear, double helicate with M‐handedness. Complete stereoselectivity is observed in solution with NMR spectroscopic data indicating the presence of one diastereoisomer. The preference for a dinuclear over mononuclear helicate can be traced to a decrease in ligand flexibility on going from 3 (saturated backbone) to 4 (unsaturated imine backbone).

Crystal structure and DNA interaction of a nickel(II) complex with N-benzyl-N ′-[2-(benzylamino)ethyl]ethane-1,2-diamine

N-Benzyl-N′-[2-(benzylamino)ethyl]ethane-1,2-diamine was prepared by reduction of its Schiff base analog. Its Ni(II) complex was synthesized and characterized. The crystal structure of the complex showed a square pyramidal structure in which a chlorine atom bridges two Ni(II) atoms in the common apical position. The dinuclear complex has two identical five-coordinate Ni(II) atoms. Interaction of the complex with calf thymus DNA was investigated by UV spectroscopy and fluorescence spectroscopy, and the results suggest that the complex binds to DNA by electrostatic interactions only. The binding constant is 1.02 × 104 mol−1 L.

Synthesis, characterization and biological activity of Schiff base analogues of indole-3-carboxaldehyde

Eight novel heterocyclic Schiff bases derived from the condensation reactions of indole 3-carboxaldehyde with different l-amino acids (histidine, glutamic acid, aspartic acid, leucine, valine) as well as with some aminophenols, have been synthesized and characterized by various spectroscopic methods (IR, MS, 1H NMR). Schiff base derivatives of indole 3-carboxaldehyde were labeled with 99mTc and radiochemical purity was above 97% which is ascertained by instant thin layer chromatography using different solvent conditions. Stability studies of all the derivatives of indole 3-carboxaldehyde was determined under physiological conditions and were stable for more than 24 h. Blood clearance showed a quick wash out from the circulation and biological half life was found to be t ½(F) = 1 h 15 min; t ½(S) = 10 h 05 min. Excellent quality radioimages of tumor bearing mice were recorded showing rapid clearance of background activity, visualization of tumor at 3 h and clearance from kidneys of histidine analogue which was further evidenced in biodistribution studies. Antimicrobial activity of these Schiff base compounds was evaluated against Bacillus subtilis, Pseudomonas fluorescence, Staphylococcus aureus, Aspergillus niger, Candida albicans and Trichophyton rubrum.

Photochemistry of a Retinal Protonated Schiff-Base Analogue Mimicking the Opsin Shift of Bacteriorhodopsin

A retinal Schiff base analogue which artificially mimics the protein-induced red shifting of absorption in bacteriorhodopsin (BR) has been investigated with femtosecond multichannel pump probe spectroscopy. The objective is to determine if the catalysis of retinal internal conversion in the native protein BR, which absorbs at 570 nm, is directly correlated with the protein-induced Stokes shifting of this absorption band otherwise known as the "opsin shift". Results demonstrate that the red shift afforded in the model system does not hasten internal conversion relative to that taking place in a free retinal-protonated Schiff base (RPSB) in methanol solution, and stimulated emission takes place with biexponential kinetics and characteristic timescales of approximately 2 and 10.5 ps. This shows that interactions between the prosthetic group and the protein that lead to the opsin shift in BR are not directly involved in reducing the excited-state lifetime by nearly an order of magnitude. A sub-picosecond phase of spectral evolution, analogues of which are detected in photoexcited retinal proteins and RPSBs in solution, is observed after excitation anywhere within the intense visible absorption band. It consists of a large and discontinuous spectral shift in excited-state absorption and is assigned to electronic relaxation between excited states, a scenario which might also be relevant to those systems as well. Finally, a transient excess bleach component that tunes with the excitation wavelength is detected in the data and tentatively assigned to inhomogeneous broadening in the ground state absorption band. Possible sources of such inhomogeneity and its relevance to native RPSB photochemistry are discussed.

Reactions of NO with Mn(II) and Mn(III) centers coordinated to carboxamido nitrogen: synthesis of a manganese nitrosyl with photolabile NO.

The Mn(II) and Mn(III) complexes of the pentadentate ligand N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide (PaPy3H; H is the dissociable carboxamide H), namely, [Mn(PaPy3)(H2O)]ClO4 (1) and [Mn(PaPy3)(Cl)]ClO4 (2), with bound carboxamido nitrogen have been isolated and characterized. The high-spin Mn(II) center in 1 is very sensitive to dioxygen, and this complex is rapidly converted into 2 upon reaction with Cl- in air. The bound carboxamido nitrogen in 1 is responsible for this sensitivity toward oxidation since the analogous Schiff base complex [Mn(SBPy3)Cl]ClO4 (4) is very resistant to oxidation. Reaction of NO with 1 affords the diamagnetic [Mn-NO]6 nitrosyl [Mn(PaPy3)(NO)]ClO4 (5). Complexes with no bound carboxamido nitrogen such as 4 and [Mn(PaPy3H)(Cl)2] (3) do not react with NO. No reaction with NO is observed with the Mn(III) complexes 2 and [Mn(PaPy3)(MeCN)]2+ either. Collectively these reactions indicate that NO reacts only with the Mn(II) center ligated to at least one carboxamido nitrogen. Both the carbonyl and N-O stretching frequencies (nu(CO) and nu(NO)) of the present and related complexes strongly suggest a [low-spin Mn(II)-NO*] formulation for 5. The alternative description [low-spin Mn(I)-NO+] is not supported by the spectroscopic and redox behavior of 5. Complex 5 is the first example of a [Mn-NO]6 nitrosyl that exhibits photolability of NO upon illumination with low-intensity tungsten lamps in solvents such as MeCN and H2O. The rapid NO loss from 5 leads to the formation of the corresponding solvato species [Mn(PaPy3)(MeCN)]2+ under aerobic conditions. Oxidation of 5 with (NH4)2[Ce(NO3)6] in MeCN affords the highly reactive paramagnetic (S = 1/2) [MnNO]5 nitrosyl [Mn(PaPy3)(NO)](NO3)2 (6) in high yield. Spectroscopic and magnetic studies confirm a [low-spin Mn(II)-NO+] formulation for 6. The N-O stretching frequencies (nu(NO)) of 5, 6, and analogous nitrosyls reported by other groups collectively suggest that nu(NO) is a better indicator of the oxidation state of NO (NO+, NO*, or NO-) in non-heme iron and other transition-metal complexes with bound NO.

Structure of [N,N´-bis(3,5-di-t-butyl-salicylidene)-2-benzyl-1,3-propanediaminato]nitridotechnetium(V) complex, TcN(bzdbsalpn), and nitrido-bridged linear polymeric chains in crystalline syn-isomer

Abstract A novel nitridotechnetium(V) complex with a tetradentate Schiff base ligand, TcN(bzdbsalpn), was synthesized by the reaction of TcNCl2(PPh3)2 and N , N´-bis(3,5-di- t-butyl-salicylidene)-2-benzyl-1,3-propanediamine (H2bzdbsalpn). Both the syn- and anti-isomers of TcN(bzdbsalpn) were formed in the solution, but recrystallization of a mixture of syn- and anti-TcN(bzdbsalpn) gave a single crystal only for the syn-isomer. X-ray crystallography showed that the syn-TcN(bzdbsalpn) was in a distorted octahedral structure. The planar tetradentate bzdbsalpn ligand coordinates to the technetium atom in an O-N-N-O equatorial plane and the six-membered Nimine-Nimine chelate ring that includes the propylene group adopts a chair conformation. The nitrido ligand (Tc≡N) is at an apical position and the Tc≡N triple bond length is 1.6 Å. Interestingly, the crystal of syn-TcN(bzdbsalpn) has a nitrido-bridged linear polymeric structure (···Tc≡N···Tc≡N···) running along the 21 screw axes parallel to the b axis. The intermolecular N···Tc distance in the syn-TcN(bzdbsalpn) crystal (∼2.8 Å) is fairly long compared with that reported for Cr(V) and Mn(V) nitrido complexes with analogous Schiff base ligands (∼2.5 Å).

Chiral biarylamido/anisole complexes of yttrium in enantioselective aminoalkene hydaroamination/cyclisation.

A group of chiral, dibasic, biaryl-bridged amido proligands containing peripheral methoxyphenyl (anisole) ligation are developed for the synthesis of new amide complexes of yttrium and lanthanum. A potentially tetradentate bis(amidoanisole) system gives, on reaction with [Y[N(SiMe(2)H)(2)](3)(THF)] a crystallographically-characterised bis complex [Y(H)] presumably as a result of low steric demand, since a more bulky version gives the target [Y[N(SiMe(2)H)(2)](THF)]. The molecular structure of the latter reveals a similar cis-alpha structure to our recently reported Schiff-base analogue. Variable-temperature NMR studies are consistent with low rigidity in the molecular structure. A potentially tridentate, amidoanisolyl/amido proligand gives complexes [M[N(SiMe(2)H)(2)](THF)(n)](M = Y, n= 1; M = La, n= 2). Chiral non-racemic versions of the above complexes were tested in the hydroamination/cyclisation of 2,2'-dimethylaminopentane to the corresponding pyrrolidine. Activities were relatively low compared to recently reported examples, and ee values were in the range 20-40% despite the well-expressed chirality of the catalysts.

Liquid Crystalline Thiadiazole Derivatives: Thiadiazole Derivatives Containing Pyridine Ring as Terminal Group

AbstractThe synthesis and mesomorphic behavior of a new series of liquid crystals containing 1, 3, 4‐thiadiazole and pyridine rings with ‐CH = N‐ central group are reported. All compounds exhibit enantiotropic smectic A mesophase, but the Schiff's base analogues have no mesomorphic behavior. The influence of the pyridine ring and thiadiazole ring is discussed.

Conformation and absolute configuration of 11,12-cyclopropyl retinal analogs – an RHF/DFT/CIS study

Ab initio RHF and DFT/B3LYP calculations at the 6-31G** level have been performed to study possible conformations of the cyclopropyl retinal Schiff base analog 3 of known absolute configuration. In both the free base and the protonated form, the geometries are determined on the diene side by optimum conjugative interaction with the three-membered ring, on the triene side by repulsive interaction with the 9-methyl group. There are three low energy conformations, in which the seven-membered ring is either in a chair or in a twist-chair conformation. To decide between these alternatives, chiroptical parameters were calculated employing the GAUSSIAN/CIS routines and compared with the CD spectrum obtained by Nakanishi et al. Of the energy-minimized geometries only two fit the experimental data. In both, the dihedral angle C12–C13, which is indicative of the relative orientation of the two chromophores, is positive.

Characterization of a conical intersection between the ground and first excited state for a retinal analog

Ab initio complete active space SCF calculations have been carried out to investigate the first excited electronic state of a retinal protonated Schiff base analog: all-trans-3,7-dimethylnona-2,4,6,8-tetraenmethylimminium cation. This model of the retinal chromophore in bacteriorhodopsin includes five conjugated double bonds as well as both pertinent backbone methyl groups. The excited state minimum that is relevant for isomerization in bacteriorhodopsin is investigated and is found to be in very close proximity to a Jahn–Teller conical intersection. The two (global) coordinates that are most effective in promoting efficient internal conversion back to the ground electronic state (by lifting the degeneracy between the ground and first excited state) are identified and discussed, and the distribution of the positive charge in the retinal analog as a function of these two coordinates is investigated.

Supramolecular motifs in metal complexes of Schiff bases. Part 5. Zinc(II)-assisted self-assembly of some bis-N,N- and N,O-bidentate Schiff bases and chiral packing modes in solid state

Zinc(II)-assisted self-assembly of a new bis-N,O-bidentate Schiff base ligand, (N-salicylidene-4,4′-diaminodiphenyl)methane (L16) with two chelating sites linked by a spacer group (-C6H4CH2C6H4-), afforded in high yield the double-helical dinuclear complex (L16 : ZnII = 2∶2). Single-crystal X-ray analyses demonstrated clearly that the two ZnII centers have a distorted tetrahedral (Td) coordination sphere with two-wrapped ligands. The analogous Schiff base, bis[4-(2-pyridylmethyleneaminophenyl]methane (L17) was also designed to self-assemble in the presence of metal ions, leading to a triple-helical dinuclear (L17∶ZnII = 3∶2) supramolecular motif. Each zinc ion has six-coordinate octahedral geometry with six nitrogens from three ligands. These unprecedented helical motifs in the solid state and solution seem to be induced by the geometrical preference for octahedral or tetrahedral coordination mode of the ZnII ion and the interligand π-stacking interactions between the spacer groups of L16 and L17. Electrospray mass spectrometry proved a very useful characterisational tool in detecting the distribution of supramolecular species in solution. Use of a N,N′-bis(2-pyridylmethylene)-1,4-diaminobenzene (L35) with a rigid phenylene spacer in its center resulted in the one-dimensional zigzag polymeric structure ((L35∶ZnII)∞ = (1∶1)∞) where the multiple π-stacking interactions operate between the aromatic rings of linking ligands. Each zinc ion is octahedrally coordinated by two N,N-bidentate arms of two different ligands and two cis oxygens from N,N-dimethylformamide as coordinating solvent.