Schiff bases, first reported by Hugo Schiff in 1864, form when a primary amine condenses with a carbonyl compound to create the characteristic azomethine, or HC=N, linkage. For more than a century and a half these molecules have served as workhorse ligands in coordination chemistry because their nitrogen, oxygen, and sometimes sulfur donor atoms grip metal ions with remarkable tenacity. The azomethine group is doubly important: it anchors the metal and it contributes directly to biological activity. Because the underlying aldehyde and amine building blocks can be swapped almost endlessly, chemists can tune the electronic and steric properties of the resulting ligands with fine precision, and decades of literature have documented antibacterial, antifungal, antioxidant, antiviral, antimalarial, anticancer, and anthelmintic behavior across this chemical family.

The research team, led by Md. Nur Amin Bitu and Md. Kudrat-E-Zahan at the University of Rajshahi with collaborators in Odisha and Riyadh, chose three amino acid precursors to build structural diversity into their ligand set. Salicylaldehyde was condensed with 6-aminohexanoic acid to give ligand L1, with L-arginine to give L2, and with DL-2-aminobutyric acid to give L3. Each condensation was carried out in a 3:1 ethanol-water mixture under reflux at roughly 80 degrees Celsius for four hours, yielding the lemon-yellow L1 at 92 percent, the yellowish-brown L2 at 93 percent, and the white L3 at 92 percent. The three ligands deliberately span an aliphatic chain, a guanidine-containing side group, and a short-chain architecture, allowing the team to probe how ligand structure governs both metal coordination and biological effect.

From these ligands the chemists generated eleven metal complexes. Ligand L1 yielded six: complexes of copper(II), manganese(II), cobalt(II), nickel(II), cadmium(II), and zirconyl(II), numbered 1 through 6. Ligand L2 produced nickel(II), cobalt(II), and manganese(II) complexes 7 through 9, while ligand L3 gave cadmium(II) and nickel(II) complexes 10 and 11. Synthesis relied on refluxing ethanolic solutions of the metal salts with the ligands, using a catalytic amount of potassium hydroxide as a deprotonating agent. The isolated solids were washed with diethyl ether and hexane and dried under vacuum, and elemental analysis confirmed purity, with carbon, hydrogen, and nitrogen deviations all within the accepted plus or minus 0.4 percent analytical tolerance.

Spectroscopy told the story of how the metals bind. In the free ligands, the azomethine stretching vibration appears at 1670 and 1634 inverse centimeters for L1 and L2 respectively; upon complexation this band shifts to between 1606 and 1641, a displacement of up to 64 inverse centimeters that signals coordination through the azomethine nitrogen. The phenolic O-H stretch likewise moved to lower frequency, and the asymmetric and symmetric carboxylate stretches shifted after complexation, demonstrating that the carboxylic oxygen also participates in binding. New medium-intensity bands between 597 and 673 and between 415 and 485 inverse centimeters were assigned to metal-oxygen and metal-nitrogen vibrations, the direct fingerprints of the coordination bonds. For ligand L3, the phenolic O-H position remained unchanged, indicating that in that ligand the phenolic oxygen stays out of the metal’s grip while the carboxylate and azomethine groups do the binding.

Electronic spectra and magnetic measurements then pinned down the geometries. Free L1 absorbs at 260 and 330 nanometers, corresponding to pi-to-pi-star transitions in the aromatic ring and n-to-pi-star transitions in the imine group; these bands red-shift and intensify upon metal binding as lone-pair electrons are donated to the metal center. New bands between 385 and 590 nanometers arise from metal-ligand charge transfer. Combining these data with effective magnetic moments, the team proposed octahedral geometries for complexes 1 through 3, tetrahedral geometries for complexes 4 through 9, and square-planar structures for complexes 10 and 11. The copper complex 1 shows a magnetic moment of 1.95 Bohr magnetons, consistent with a single unpaired electron in a Jahn-Teller distorted octahedral field, while the near-diamagnetic nickel complex 11 at 1.16 Bohr magnetons fits a square-planar d8 configuration. The authors are candid that single-crystal X-ray diffraction could not be obtained because the complexes are microcrystalline or amorphous, so these assignments rest on convergent but indirect spectroscopic and computational evidence.

Thermogravimetric analysis in nitrogen up to 800 degrees Celsius traced multi-stage decomposition pathways consistent with the proposed formulas. Complex 1 lost its carboxylate portions between 240 and 280 degrees Celsius with a 14.20 percent weight loss against a calculated 14.47 percent, and finally resolved to copper or copper oxide above 400 degrees. Complexes 2 and 3 decomposed in four stages beginning with lattice water loss around 50 to 180 degrees, and complexes 4 through 6 each released water, carboxylate, and organic fragments before collapsing to metal oxides between 450 and 630 degrees. The authors note that without complementary TG-MS or TG-FTIR techniques the decomposition assignments remain proposed rather than proven, an honest limitation they flag for future work.

Antibacterial testing by disc diffusion against Bacillus cereus, a Gram-positive strain, and Escherichia coli, a Gram-negative strain, revealed that complexation dramatically boosts activity compared with the free ligand. The cadmium complex 5 was the standout, producing a zone of inhibition of 32 plus or minus 0.26 millimeters against B. cereus, essentially matching kanamycin-30, and 24 plus or minus 0.26 millimeters against E. coli, below the antibiotic’s 29 plus or minus 0.10 millimeters. The copper complex 1 also performed well against both organisms. The team explains the enhancement through chelation theory: coordination reduces the polarity of the metal ion and delocalizes electron density over the chelate ring, raising lipophilicity so the complexes penetrate bacterial membranes more readily and reach intracellular targets such as DNA and enzymes. The authors stress that cadmium complexes require cytotoxicity evaluation against human cell lines before any therapeutic claim can be made, and that minimum inhibitory concentration testing was not performed, making these results preliminary and exploratory.

The computational arm of the study added mechanistic depth. Density functional theory calculations using the BP86 functional and def2-SV(P) basis sets in ORCA, with a conductor-like polarizable continuum model for water, showed that complex 5 has the most negative single-point energy of the series at minus 6299.1495 atomic units, marking it as the most thermodynamically stable, while complex 4 carries the largest dipole moment. The HOMO-LUMO gap of 2.571 electron volts and the highest chemical hardness of 1.2855 electron volts identified free ligand L1 as the most kinetically stable species, whereas complex 4, with the smallest gap and hardness, is the most reactive. Molecular docking against the 16S ribosomal RNA subunit of Thermus thermophilus, the same target through which kanamycin halts bacterial translation, showed that complex 1 achieved the strongest rRNA binding energy of the series, with the metal complexes generally matching or exceeding the affinities of kanamycin and pactamycin. The researchers caution that AutoDock Vina’s scoring function was developed for organic molecules and lacks validated metal parameters, so the docking results are qualitative indicators rather than mechanistic proof, and that complex 5 may act through additional targets such as membrane disruption. Together, the synthesis, spectroscopy, theory, and bioassays sketch a coherent picture of how simple amino acid-derived Schiff bases, when wrapped around the right metal, can become surprisingly potent antibacterial candidates.

Subject of Research: Transition metal complexes of salicylaldehyde-derived Schiff base ligands and their antibacterial activity

Article Title: Synthesis and antibacterial evaluation of transition metal complexes derived from salicylaldehyde based Schiff base ligands supported by DFT studies and molecular docking

Article References: Bitu, M. N. A., Uddin, S., Mohapatra, R. K., Azam, M., Mohapatra, P. K., Dash, G. C., Raval, M. K., & Kudrat-E-Zahan, M. (2026). Synthesis and antibacterial evaluation of transition metal complexes derived from salicylaldehyde based Schiff base ligands supported by DFT studies and molecular docking. Discover Chemistry, 3(1), Article 454. https://doi.org/10.1007/s44371-026-00900-5

Image Credits: AI Generated

DOI: 10.1007/s44371-026-00900-5

Keywords: Schiff base, salicylaldehyde, transition metal complexes, antibacterial activity, DFT, molecular docking, coordination chemistry, kanamycin, 16S rRNA, cadmium complex, chelation theory, antimicrobial resistance

A new study published in the open-access journal Results in Chemistry by Menaka Bhuyan and Jubaraj B. Baruah of the Indian Institute of Technology addresses this challenge with an unusual design philosophy. Rather than building a probe that reacts chemically with aldehydes, a strategy that consumes both the analyte and the sensing site, the team engineered two fluorescent molecules that recognize salicylaldehyde purely through non-covalent binding. The probes, named anambenz and animbenz, both carry an anthracene fluorophore, one of the most reliable light-emitting units in fluorescence chemistry, connected through a phenylene diamine-derived linker to an electron-withdrawing benzoyl group bearing a hydrogen-bond acceptor. A planar aryl unit with a hydrogen-bond donor, either an amino or an imino group, sits between the two ends, creating a molecule with three distinct faces above which an aromatic analyte can stack.

The synthetic route to the two probes is elegantly economical. Both compounds arise from the condensation of 3,4-diaminobenzophenone with 9-anthracenecarboxaldehyde, but divergent reaction conditions steer the chemistry toward different products. Refluxing in methanol for 24 hours delivers anambenz in an 80 percent yield, retaining a free amino group on the central ring. Heating the same starting materials in dimethylformamide with acetic acid for two days at 120 degrees Celsius instead promotes cyclization, furnishing the imino-containing animbenz in 60 percent yield. The structures were confirmed by proton and carbon-13 nuclear magnetic resonance spectroscopy, infrared spectroscopy, and high-resolution mass spectrometry, and the crystal structure of anambenz, solved by single-crystal X-ray diffraction, revealed a U-shaped geometry in which the benzoyl carbonyl projects away from the anthracene ring, with the crystal packing governed by nitrogen-hydrogen to nitrogen hydrogen bonds and weak carbon-hydrogen to pi contacts.

In dimethylformamide solution, anambenz absorbs strongly at 345 nanometers and emits a broad, featureless band at 475 nanometers when excited at that wavelength, while animbenz absorbs at the same wavelength but emits at 425 nanometers with the characteristic vibrational structure of anthracene derivatives. Both probes display solvatochromic behavior, with their absorption and emission shifting across solvents, and both suffer fluorescence quenching in protic media, with water quenching more strongly than ethanol, which in turn quenches more than methanol. Crucially, the emission of each probe in dimethylformamide remained stable for over an hour, establishing a reliable baseline for analytical work.

The decisive experiment came when the researchers exposed each probe to a panel of thirteen aromatic aldehydes, including 4-hydroxybenzaldehyde, 2,4,6-trihydroxybenzaldehyde, 2-carboxybenzaldehyde, 2-hydroxynaphthaldehyde, 2,3-dihydroxybenzaldehyde, nitro-substituted benzaldehydes, 4-bromobenzaldehyde, 4-methoxybenzaldehyde, and 4-(diethylamino)salicylaldehyde. Against this crowded field, salicylaldehyde stood alone: it completely quenched the emission of both probes, while the other aldehydes produced either partial, substrate-specific changes or no effect at all. Some near-misses were instructive. 2,3-Dihydroxybenzaldehyde actually enhanced the fluorescence of anambenz and shifted its emission peak to 480 nanometers, and 4-(diethylamino)salicylaldehyde caused partial quenching with a shift to 507 nanometers, but only salicylaldehyde silenced the anthracene emission entirely.

Quantitative titrations revealed Stern-Volmer plots that were linear, pointing to dynamic quenching arising from collisions between excited probe molecules and the analyte rather than the formation of stable ground-state complexes. Time-correlated single-photon counting added a deeper layer of insight. Anambenz alone decays through a tri-exponential profile dominated by a 4.93-nanosecond pathway accounting for 85.54 percent of the emission. Upon adding salicylaldehyde, that dominant fast pathway collapses, and the profile reorganizes so that nearly half the emission follows an ultrafast 0.02-nanosecond route while a new 7.74-nanosecond component emerges, evidence that the interaction redirects the excited-state dynamics. Animbenz, by contrast, shows a single 1.67-nanosecond lifetime that barely changes to 1.68 nanoseconds in the presence of the aldehyde, a signature of purely dynamic quenching that helps explain why its detection limit, 4.8 times ten to the minus two molar, is far weaker than the 181 micromolar limit achieved by anambenz.

Proton NMR titrations confirmed that the ground-state interaction between anambenz and salicylaldehyde is genuinely feeble: the phenolic hydroxyl of the aldehyde shifted by a mere 0.009 parts per million, the imine proton of the probe moved by the same tiny amount, and the amino protons were untouched. The selectivity therefore cannot rest on strong binding. To understand what does control it, the team turned to molecular modeling. Density functional theory calculations at the B3LYP level with a 6-311+G(d,p) basis set, followed by noncovalent interaction region analysis using the Multiwfn program, showed that salicylaldehyde positions itself above the anthracene ring of both probes in an orientation that enables an OH-pi interaction between its hydroxyl group and the pi cloud of the fluorophore. The structurally similar 4-hydroxybenzaldehyde, lacking the ortho hydroxyl geometry, ends up either perpendicular to the anthracene unit or displaced to a remote end of the probe, unable to make the crucial contact.

Time-dependent DFT calculations, performed with the dielectric constant of dimethylformamide to mimic the experimental solution, reinforced the picture. The calculated absorption maxima of the salicylaldehyde assemblies carried lower oscillator strengths than those of the 4-hydroxybenzaldehyde assemblies, 0.22 versus 0.24 for animbenz and 0.41 versus 0.43 for anambenz, meaning a reduced probability of the radiative transition and hence stronger quenching. Frontier orbital analysis showed why the geometry matters so much: in the salicylaldehyde assemblies, both the highest occupied and lowest unoccupied molecular orbitals localize on the anthracene portion, whereas the 4-hydroxybenzaldehyde assemblies distribute the orbitals differently across the imine and carbonyl regions. The precise way an analyte hovers over the probe, in other words, rewrites the electronic structure of the whole assembly and with it the fluorescence outcome.

How does this approach compare with existing salicylaldehyde sensors? The literature includes metal-organic frameworks based on europium and zinc, a terbium coordination polymer, a europium zirconium oxo-cluster, and organic turn-on probes, with reported detection limits spanning from 0.259 micromolar for a zinc benzimidazolate framework up to 58.2 micromolar and beyond. Several of these systems are more sensitive than the new probes, and a terbium polymer even allows naked-eye detection, but that color change is not specific, since benzaldehyde triggers it too, and amine-based turn-on probes suffer interference from other aldehydes. The distinctive achievement of anambenz and animbenz is selectivity through molecular recognition: only salicylaldehyde, of thirteen aldehydes tested, quenches the emission completely, and competitive experiments showed that the quenched state cannot be reversed by adding 4-hydroxybenzaldehyde, while salicylaldehyde retains its quenching power even in the presence of that competitor. The probes also functioned in solutions containing milk, hinting at practical utility in food and product screening.

The authors are candid about the limits. A detection limit of 181 micromolar falls well short of the concentrations implied by the predicted no-effect threshold, so these probes are not yet suited to environmental screening at trace levels. Where they could shine instead is industrial spill alerting and process control, situations in which salicylaldehyde is present at high concentrations and in which distinguishing it from structurally related aldehydes matters more than ultimate sensitivity. More broadly, the study demonstrates a design principle with wide reach: by arranging a fluorophore, a hydrogen-bond donor, and a hydrogen-bond acceptor on a single scaffold, and by letting subtle differences in pi-stacking and OH-pi geometry dictate the excited-state fate, chemists can build sensors that discriminate between molecules as similar as two hydroxybenzaldehydes without ever touching them chemically. As the authors conclude, probes that modulate emission through molecular recognition offer a large and largely unexplored space for developing high-efficiency, non-invasive detection of reactive compounds in the world around us.

Subject of Research: Selective fluorescence detection of salicylaldehyde using anthracene-based molecular recognition probes

Article Title: Efficient and selective detection of salicylaldehyde

Article References: Bhuyan, M., & Baruah, J. B. (2026). Efficient and selective detection of salicylaldehyde. Results in Chemistry, 31, Article 103952. https://doi.org/10.1016/j.rechem.2026.103952

Image Credits: AI Generated

DOI: 10.1016/j.rechem.2026.103952

Keywords: salicylaldehyde, fluorescent probe, anthracene, fluorescence quenching, molecular recognition, OH-pi interaction, DFT calculations, Stern-Volmer, detection limit, aromatic aldehydes, Results in Chemistry, sensor chemistry

The research team, led by Yogesh Bhaskar Singh Tanwer, Suman Sourabh, and Sabyasachi Bhunia of the Central University of Jharkhand, together with Sanchari Pal and Debjit Das of Triveni Devi Bhalotia College, combined three simple ingredients in a single flask: a substituted salicylaldehyde, either 4-hydroxycoumarin or 1,3-dimethylbarbituric acid, and an electron-rich arene such as 1,3,5-trimethoxybenzene. Heating this mixture at 90 degrees Celsius in a mixture of lemon juice and ethanol produced the desired fused chromene products in yields ranging from 74 to 87 percent for the chromeno[4,3-b]chromene series and good to excellent yields for the chromeno[2,3-d]pyrimidine analogues. No metals, no exotic reagents, no chromatographic purification—just filtration and a wash with aqueous ethanol in most cases.

The appeal of multicomponent reactions lies in their efficiency. Rather than assembling a target molecule step by step, isolating and purifying intermediates at each stage, a multicomponent reaction stitches three or more building blocks together in one operation. This convergence saves time, energy, solvent, and manpower, which is why such reactions are prized in pharmaceutical and combinatorial chemistry. But traditional versions of these reactions often rely on volatile organic solvents and toxic or costly metal catalysts, undermining their green credentials. The Indian team’s approach sidesteps both problems by using a food-derived catalyst in a largely benign medium.

Lemon juice has been attracting growing attention as a biocatalyst in recent years. It is cheap, widely available, water-soluble, biodegradable, and non-toxic, and its natural acidity—derived primarily from citric acid—allows it to substitute for harmful metallic and non-metallic acid catalysts in a range of organic transformations. In the new study, the researchers found that lemon juice alone in water failed to deliver any product even after 24 hours of reflux, largely because the organic starting materials dissolve poorly in the aqueous juice. Adding ethanol as a co-solvent solved the solubility problem dramatically: with 2.0 milliliters of lemon juice and 1.5 milliliters of ethanol at 90 degrees Celsius, the model reaction between salicylaldehyde, 1,3,5-trimethoxybenzene, and 4-hydroxycoumarin delivered the product 4a in 89 percent yield.

With the optimized conditions in hand, the team explored how broadly the method could be applied. A variety of salicylaldehyde derivatives reacted smoothly with 1,3,5-trimethoxybenzene and 4-hydroxycoumarin, furnishing nine different chromeno[4,3-b]chromene products in 74 to 87 percent yields. Switching the coumarin component for 1,3-dimethylbarbituric acid redirected the chemistry toward chromeno[2,3-d]pyrimidines, seven derivatives of which were obtained in good to excellent yields. The researchers also demonstrated that dibenzylaniline, another strongly electron-rich arene, could serve as the arene component, giving the corresponding products in good yields, including a chromeno[2,3-d]pyrimidine in 78 percent yield.

The substrate scope does have a clear boundary. The reaction tolerates a range of substituents on the salicylaldehyde ring, but it works only with strongly electron-rich arenes. Weaker candidates such as mesitylene, dimethoxybenzene, and methoxynaphthalene showed little to no activity, a limitation that reflects the electrophilic character of the key intermediate in the reaction pathway. Even so, the products obtained represent a class of compounds that had not previously been accessible through a general protocol using direct arene functionalization at the 7 and 5 positions, making the method a genuine addition to the synthetic toolbox.

To understand how the reaction actually works, the team ran a series of control experiments. When salicylaldehyde and 1,3,5-trimethoxybenzene were heated together without the coumarin component, no adduct formed, ruling out a direct coupling pathway. When salicylaldehyde and 4-hydroxycoumarin were combined under the optimized conditions, a condensed product—labeled intermediate B—formed in 66 percent yield within six hours. The researchers isolated this intermediate, confirmed its structure by nuclear magnetic resonance spectroscopy, and then showed that reacting it with 1,3,5-trimethoxybenzene gave the final chromeno[4,3-b]chromene in 91 percent yield. This established that the three-component reaction proceeds through intermediate B rather than through a different sequence.

Based on these observations, the authors proposed a plausible mechanism. The acidity of the lemon juice first promotes a Knoevenagel condensation between the salicylaldehyde and the 4-hydroxycoumarin, generating the electron-poor Michael acceptor B. The electron-rich arene then adds to this acceptor in a Michael-type addition, producing an intermediate containing a tertiary carbon center. Finally, an acid-driven intramolecular ring closure followed by dehydration delivers the fused chromene product. In other words, the citric acid in the juice orchestrates every key step of the cascade, from initial condensation to final cyclization, without any metal assistance.

Practical considerations further strengthen the case for the method. The structures of two representative products were unambiguously confirmed by single-crystal X-ray crystallographic analysis, and all compounds were characterized by proton and carbon NMR spectroscopy, high-resolution mass spectrometry, and elemental analysis. Crucially, the team demonstrated that the reaction can be scaled up: a 10-millimole-scale run of the model compound proceeded with effectiveness and yields comparable to the small-scale experiments, suggesting genuine potential for commercial and industrial application. Because nearly all products precipitate from the reaction mixture, purification requires only filtration and washing, eliminating extraction steps, column chromatography, and the large volumes of harmful organic solvents they consume.

The significance of the work extends beyond the specific molecules made. Chromene derivatives are distributed widely in natural products, drugs, and edible plants, and their fused hybrids with coumarin or barbituric acid units display a striking range of pharmacological activities, including antitumor, anti-inflammatory, cytotoxic, antioxidant, antithrombotic, and antiplatelet effects, along with useful photophysical properties. A hybrid framework combining chromene with other bioactive analogues may incorporate the characteristics of both and enhance biological activity, which is precisely why synthetic chemists keep seeking better ways to build them. By replacing toxic metals and hazardous solvents with a kitchen staple, the Indian team has shown that the principles of green chemistry—waste prevention, safer solvents, catalysis, and energy efficiency—can be honored without sacrificing yield, scope, or scalability. The study was funded by the Science and Engineering Research Board and the University Grants Commission of India, and it stands as a vivid reminder that sometimes the most sustainable catalyst is sitting in the refrigerator.

Subject of Research: Lemon juice-mediated green synthesis of chromeno[4,3-b]chromene and chromeno[2,3-d]pyrimidine derivatives via one-pot three-component reactions

Article Title: Lemon juice mediated environmentally benign synthesis of functionalized chromeno[4,3-b]chromene/chromeno[2,3‐d]pyrimidine derivatives via one-pot three component reaction

Article References: Lemon juice mediated environmentally benign synthesis of functionalized chromeno[4,3-b]chromene/chromeno[2,3‐d]pyrimidine derivatives via one-pot three component reaction. (n.d.). https://doi.org/10.1007/s44509-026-00001-7

Image Credits: AI Generated

DOI: 10.1007/s44509-026-00001-7

Keywords: lemon juice, green chemistry, multicomponent reaction, chromene, chromenopyrimidine, organocatalysis, salicylaldehyde, 4-hydroxycoumarin, barbituric acid, Knoevenagel condensation, sustainable synthesis, metal-free catalysis