Schiff base ligands and their metal complexes represent a significant area of research in coordination chemistry due to their structural versatility, ease of synthesis, and ability to modulate the chemical and biological behaviour of metal ions. Among them, polydentate Schiff bases, particularly pentadentate, hexadentate, and heptadentate ligands, have earned considerable attention for their strong chelating ability, forming stable complexes with mid-to-late 3d-metal ions, and for their diverse physicochemical, biological, and functional properties. This review provides a comprehensive overview of recent research reported (2014-2025), focusing on recent advances in the synthesis, coordination behaviour, structural characterization, and functional applications of such metal complexes derived primarily from salicylaldehyde and its derivatives. These Schiff base ligands, featuring five to seven donor atoms and various donor sets, are systematically classified based on their denticity and donor types to highlight structure-property relationships. Representative findings include diverse coordination geometries ranging from square-pyramidal and trigonal-bipyramidal to octahedral geometries, supported by spectroscopic and single-crystal X-ray diffraction analyses. The review further summarises key findings such as enhanced antimicrobial, antioxidant, cytotoxic, and DNA-binding activities upon metal coordination, as well as notable luminescence, magnetic, and electrochemical behaviours. Structure-activity correlations are discussed in relation to ligand denticity, donor sets, and metal-ion identity.

In this study, a series of achiral/chiral ferrocene fuctionalized amino precursors were used to develop a new series of homoleptic Ni(II)-dithiocarbamate complexes: 1, (R,R)-2, (S,S)-3, (R,R)-4 and (S,S)-5. These compounds incorporate chirality, pendent amido, and ferrocenyl groups within their ligand frameworks. The synthesis and composition of these complexes were confirmed through microanalysis, advanced spectroscopic and single crystal X-ray diffraction studies. Complex 1 crystallised in the monomeric centrosymmetric P21/c space group, with two dithiocarbamate ligands coordinated to the Ni(II)-center in a kappa 2S,S-chelating mode, giving a square planar geometry around the Ni(II)-center. The experimentally obtained structural parameters were consistent with those predicted by density functional theory (DFT) calculations. Thermogravimetric analysis revealed the thermal stability and degradation patterns of all complexes. Notably, the molecules of 1 adopted a stereochemical conformation that opens numerous weak intermolecular interactions, through the mapping of molecular electrostatic potential, facilitating the formation of a 3D supramolecular assembly with significant voids. The optimised geometries for all complexes at the B3LYP/LanL2DZ level were validated by comparing their experimental structural parameters and lambda max values. Interestingly, when compared to free chiral amine precursors, the combined effects of several pharmacophores and chirality were found to increase the binding affinity of these complexes with the active sites of TNF-alpha protein (TNF-alpha), as confirmed by in-silico and electrochemical studies. The integration of chirality and multiple pharmacophores significantly improved bioactivity, underscoring their promise in anticancer drug development.

Thiosemicarbazones (TSCs) are an important class of sulphur-containing Schiff base ligands, characterised by thione-thiol tautomerism and versatile coordination through sulphur and nitrogen donor atoms. Owing to their closed-shell d10 electronic configuration and flexible coordination behaviour, Zn(II) and Cd(II) ions form structurally diverse TSC-complexes with tunable physicochemical and functional properties. This review summarises recent studies (2020-2025) on Zn(II)-and Cd(II)-based thiosemicarbazone complexes, focusing on their synthesis, coordination modes, structural features, and structure-property relationships with comparative reference to related Mn, Fe, Co, Ni, Cu, and Hg analogues. Particular attention is given to N, S-bidentate and N, N, S/N, S, O-tridentate coordination patterns and their influence on molecular geometry and stability, as established by crystallographic and spectroscopic analyses. The discussion emphasises how metal coordination modifies electronic structure, lipophilicity, and intermolecular interactions, thereby affecting multifunctional behaviour. Reported antimicrobial, antifungal, anticancer, antioxidant, catalytic, and DNA-binding activities are comparatively analysed to highlight emerging trends and structure-activity relationships. Complementary density functional theory (DFT) calculations and ADMET analyses are also used to rationalise metal-induced electronic effects and guide the design of sulphur-coordinated TSC-complexes with improved functional performance.

A new series of N,O-Schiff base monometallic complexes with pendant alcoholic groups, formulated as [M-II-kappa(2)-bis-N,O-bidentate Schiff base-L-1/L-2] {L-(1) over bar, M-II = Ni (1), Cu (2), or Zn (3); L-(2) over bar, M-II = Ni (4), Cu (5), or Zn (6)}, is reported herein. These complexes were synthesized by reacting monobasic N,O-Schiff bases 2-[(2-Hydroxyphenyl methylene)amino]benzeneethanol (HL1) and 2-[(2-Hydroxynaphthylmethylene)amino]benzeneethanol (HL2) with divalent metal ions in absolute ethanol at room temperature. The complexes were characterized by microanalysis and a range of spectroscopic methods (H-1 and C-13{H-1} NMR, FT-IR, UV-vis absorption). The molecular structures of HL2 and complex 4 were determined using single-crystal X-ray diffraction (SCXRD). The X-ray data confirmed the presence of intramolecular and intermolecular hydrogen bonding interactions involving phenolic O-H, imine, and alcoholic moieties. Hirshfeld analysis quantified these interactions. Magnetic moment data and UV-vis spectra suggest square-planar coordination around the Nickel(II)/Copper(II) centers and a tetrahedral geometry around the Zinc(II) centers, further confirmed by SCXRD and DFT calculations. Notably, fluorescence studies revealed strong visible-range fluorescence upon UV excitation for complex 1. The complexes exhibited thermal stability up to similar to 150 degrees C, with HOMO-LUMO band gaps ranging from 3.4 to 3.7 eV, indicating non-conducting behavior. In vitro antimicrobial assays demonstrated that Zinc(II) complex 3 exhibited significant antifungal activity, while Zinc(II) complex 6 showed notable activity against gram-positive bacteria and fungi. In-silico studies were also performed to reinforce the rationalization of the experimental findings.

Two secondary diamines viz. N,N'-bis{3-( p-methoxybenzylamino)propyl}piperazine (H2L1) 2 L 1 ) and N,N'-bis{3-(p- chlorobenzylamino)propyl}piperazine (H2L2) 2 L 2 ) holding N,N'-bispropylpiperazine linkers have been prepared and subsequently used to derive a new series of N,N'-bis(3-dithiocarbamatopropyl) piperazine bridged metallomacrocyclic complexes [M(II)2-mu 2-bis-{(kappa 2S,S-S2CN(R)C3H6)2piperazine}] 2- mu 2-bis-{( kappa 2 S,S-S 2 CN(R)C 3 H 6 ) 2 piperazine}] wherein R = p-methoxybenzyl, M = Ni(II) 1, Cu(II) 2, Zn(II) 3; R = p-chlorobenzyl, M = Ni(II) 4, Cu(II) 5, Zn(II) 6. The formation and purity of all the metallomacrocyclic dithiocarbamate complexes were verified by microanalysis and standard methods such as HRMS, NMR, IR and UV-Visible absorption spectroscopy and corroborated by density functional theory calculations. The experimental (magnetic susceptibility and UV-Visible) and theoretical calculations suggest a square planar/distorted square planar environment around nickel(II)/copper(II) and tetrahedral/distorted tetrahedral environment around zinc(II) centres in 1-6. Thermogravimetric study was carried out on 1-6 to study their thermal stability and degradation behaviour. Notably, TG curves of compounds 2, 3 and 5 gave a stable residual mass corresponding to corresponding metal sulphides (MS). Notably, the calculated HOMO-LUMO gaps (1.19-1.33 eV) for Cu(II)-dithiocarbamate 2 and 5 indicates their semiconducting nature. The potentials of these metallomacrocycles as a molecular probe for optical sensing of environmentally hazardous heavy metal ions ca Pb(II), Cd(II) and Hg(II) were further examined by using UV-Visible and fluorescence spectroscopies.

We report a novel series of chiral monometallic dithiocarbamate complexes with pendant phenolic groups, formulated as [M{kappa S-2<^>S-S2CN(CH2PhOH)(CH(S-CH3))(NaPh)}(2)] (M = Ni(II) S,S-1, Cu(II) S,S-2, Zn(II) S,S-3) and [M{kappa S-2<^>S-S2CN(CH2PhOH)(CH(R-CH3))(NaPh)}(2)] (M = Ni(II) R,R-4, Cu(II) R,R-5, Zn(II) R,R-6). These compounds were synthesized through a process involving chiral amino precursors S-HL1, R-HL2, CS2 and the corresponding metal acetates. All the compounds have been characterized by microanalysis and standard spectroscopic methods such as H-1 and C-13{H-1}NMR, IR, UV-visible absorption and EPR spectroscopy. The spectral data suggest a square planar coordination geometry around the nickel(II) and copper(II) centers and a tetrahedral coordination geometry around zinc(II), which is corroborated by density functional theory calculations. The unprecedented molecular structures of imine precursors S-I, R-I and Ni(II)-dithiocarbamate complex S,S-1 were elucidated by single crystal X-ray diffraction (SCXRD), and their crystal packing patterns were studied. Evidently, the change in chirality could not induce changes in the donor-acceptor sites of S-I and R-I, and their molecules are primarily stabilized by O-H & ctdot;N and C-H & ctdot;pi interactions, forming a 2D sheet-like structure in the ab-plane. Notably, the chiral S,S-1 complex crystallized in a monomeric achiral space group (triclinic, P1) in which two dithiocarbamate ligands are bonded to the nickel(II) ion in a S<^>S chelating mode forming a square planar geometry around the metal center. The photophysical properties of all the compounds have been investigated using UV-visible absorption, emission, and thermogravimetric analyses. Compounds exhibited intense blue photoluminescence with maximum emissions in the 330-336 nm region upon excitation in the UV region. A molecular docking study was performed to validate the potentials of these compounds in protein-ligand interactions against B-DNA Dodecamer (PDB Id: 1BNA) and cyclins (PDB Id: 1w98), which are indeed essential proteins of the cell cycle, and their proper functioning is necessary for the human health.

This paper outlines a facile synthesis of chiral bisimines R,R-(Thiophene-2,5-diyl)bis(N-(1-phenylethyl)methanimine) R,R-BI-1, S,S-(Thiophene-2,5-diyl)bis(N-(1-phenylethyl)methanimine) S,S-BI-2 and their reduced products R,R-(Thiophene-2,5-diyl)bis(N-(1-phenylethyl)methanamine) R,R-DA-1, S,S-(Thiophene-2,5-diyl)bis(N-(1-phenylethyl) methanamine) S,S-DA-2 holding thiophene spacers. The new derivatives were suitably characterized by microanalysis, standard spectroscopic techniques (H-1, C-13 NMR, FTIR, UV-visible absorption). Single crystal X-ray diffraction (SCXRD) method was used to study the supramolecular structures of R,R-BI-1 and S,S-BI-2, sustained primarily by CH & mldr;pi intermolecular contacts which are well supported by molecular electrostatic potential (MESP). Quantification of short contacts existing in the crystal packing of these molecules was accomplished by Hirshfeld surface and fingerprint plots calculations. The geometry of all the molecules has been optimized by using a density functional theory calculation and the theoretical data were compared well with the experimental outcomes. Further, the calculated HOMO-LUMO band gaps for R,R-BI-1, S,S-BI-2, R,R-DA-1 and S,S-DA-2 (4.05-5.30 eV) suggests their non-conducting nature. Moreover, virtual screening of these nitrogenous compounds has been performed by molecular docking study to propose their potentials as biologically relevant molecules.

An array of mononuclear dithiocarbamate complexes [M-II{k(2)S(boolean AND)S-S2CN(R)CH2C6H4OH}(2)] (R=2-picolyl, M=Ni(II)1, Cu(II)2, Zn(II)3, R=3-picolyl, M=Ni(II)4, Cu(II)5, Zn(II)6); incorporating heterocyclic backbone were synthesised from (2-hydroxybenzyl)(2-picolyl)amine (HL1) and (2-hydroxybenzyl)(3-picolyl)amine (HL2) precursors. The formulation of these complexes was examined using various spectroscopic and analytical techniques (H-1 NMR, C-13 NMR, FTIR, UV-visible, Fluorescence, TGA/DTA) and further corroborated by DFT level calculation. Notably, precursors HL1 and HL2 exhibits maximum emission in the visible nm region (ca 502 and 408 nm) upon excitation of ultraviolet radiation at similar to 280 nm with concomitant Stokes shift ca 220 and 128 nm, respectively. The emission properties of these evidently suppressed after complexation with metal ions. Stability of 1-6 were determined by thermogravimetric analysis. The magnetic moment along with UV-visible of 1-6 suggests square-planar environment around Ni-II and Cu-II and tetrahedral environment around Zn-II in 1-6 which is in accord with their optimized geometries. Compounds were screened for in- vitro antimicrobial activity against E. coli, P. aeruginosa, S. aureus, S. pyogenes, C. albicans, A. niger, A. clavatus by broth dilution method. Molecular docking study was performed to rationalize the results.

Schiff base ligands have received attention due to their versatile coordination abilities and potential applications in medicinal and biological fields. This investigation offers an in-depth summary of the current advancements in comprehending the diverse biological impacts demonstrated by 3d-metal complexes of N, O-donor multidentate Schiff base ligands derived from salicylaldehyde and its derivatives. The coordination of these ligands with 3dmetal ions results in the formation of stable complexes. The increasing interest in the creation and production of compounds involving 3d-metals with biologically active ligands has led to significant advances in the field of coordination chemistry. The investigations incorporate a range of biological aspects, including anticancer, antifungal, antibacterial, antioxidant, antiproliferative, cytotoxic and SOD activities. The metal complexes exhibit enhanced biological activities compared to their parent ligands, attributed to the coordination of the metal ion and the resulting structural modifications. Furthermore, the manuscript discusses the structure-activity relationships that have been established to understand the underlying mechanisms of biological activities of these complexes. Molecular docking studies and spectroscopic techniques have been employed to elucidate the binding interactions between the metal complexes and relevant biomolecules, shedding light on their potential mode of action. These multifaceted complexes, with diverse biological properties, hold promise as valuable candidates in medicinal chemistry and biological research.

Chiral alpha-iodoamides (S)-IA-1, (R)-IA-2, (S)-IA-3 and (R)-IA-4 were synthesized and characterized prior to use in the synthesis of four chiral ferrocenyl secondary amines viz. (S)-2-(ferrocenylmethylamino)-N-(1-phenylethyl) acetamide, (S)-FA-5, (R)-2-(ferrocenyl methylamino)-N-(1-phenylethyl)acetamide, (R)-FA-6, (S)-2-(ferrocenylmethylamino)-N-(1-(naphthalen-1-yl)ethyl)acetamide, (S)-FA-7 and (R)-2-(ferrocenylmethylamino)-N-(1(naphthalen-1-yl)ethyl)acetamide, (R)-FA-8. The purity and composition of the compounds were ascertained by elemental, 1H, 13C NMR, FTIR, UV-visible emission spectral and X-ray diffraction methods. The formation of diverse supramolecular assemblies sustained by several NH...O, CH...O and CH...I intermolecular hydrogen bonding interactions was confirmed by single crystal X-ray diffraction (SCXRD). The impact of Eh and chirality on the anti-proliferative activity of these compounds has been explored. Notably, R-enantiomers are found to be superior to S-enantiomers in the studied MCF 7, IMR 32, HepG2 and L132 cell lines of human origin. In instance, (R)-FA-6 has demonstrated superior activity than cisplatin against MCF 7 (IC 50: 31.38 +/- 0.24 mu M) and HepG2 (IC 50: 18.78 +/- 0.14 mu M). Further research, including electrochemical, DFT calculations and a docking analysis, was performed to rationalize and confirm the results.

Potassium salt of N,N-Bis(2-dithiocarbonatoethyl)-4-methylbenzenesulfon amide (K2xan) was synthesized and characterized prior to use in the progress of a 24-membered binuclear metallomacrocyclic compound [NiII2-µ2-bis-{(κ2S,S-S2COCH2CH2)2N(Ts)}] (1) and a synthetically challenging 16-member organic functional macrocycle 6,14-ditosyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dithione (2). Compounds have been characterized by using microanalysis, standard spectroscopic and crystallographic techniques. A plausible mechanism for the formation of compound 2 has been established based on experimental evidence. Compounds 1 and 2 fluoresces at 377 and 293 nm upon excitation at 314 and 232 nm, respectively. The single crystal X-ray diffraction (SCXRD) study revealed a distorted square planar coordination geometry around NiII-centre in 1 which is consistent in the solution of non-coordinating solvents such as CH2Cl2. In a coordinating solvent such as DMSO, however, charge transfer bands 421, 481 nm vanished and characteristic d-d transition band at 698 nm appeared which suggest a change in the coordination geometry around NiII centre from square planar (in CH2Cl2) to octahedral complex (in DMSO). This solvatochromic behaviour of NiII-xanthate complex 1 is supplemented by reversible thermochromic behaviour over a wide temperature ca 30–90°C. Notably, thermal degradation of NiII-xanthate complex 1 gave a stable residual mass that corresponds to NiS. The X-band EPR, UV–visible and TD-DFT studies and electrochemical investigations have been performed to rationalize the results and establish the structure-property correlation.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Potassium salt of N,N-Bis(2-dithiocarbonatoethyl)-4-methylbenzenesulfon amide (K2xan) was synthesized and characterized prior to use in the progress of a 24-membered binuclear metallomacrocyclic compound [NiII2-mu 2-bis-{(kappa 2S,S-S2COCH2CH2)2N(Ts)}] (1) and a synthetically challenging 16-member organic functional macrocycle 6,14-ditosyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dithione (2). Compounds have been character-ized by using microanalysis, standard spectroscopic and crystallographic techniques. A plausible mechanism for the formation of compound 2 has been established based on experimental evidence. Compounds 1 and 2 fluo-resces at 377 and 293 nm upon excitation at 314 and 232 nm, respectively. The single crystal X-ray diffraction (SCXRD) study revealed a distorted square planar coordination geometry around NiII-centre in 1 which is consistent in the solution of non-coordinating solvents such as CH2Cl2. In a coordinating solvent such as DMSO, however, charge transfer bands 421, 481 nm vanished and characteristic d-d transition band at 698 nm appeared which suggest a change in the coordination geometry around NiII centre from square planar (in CH2Cl2) to octahedral complex (in DMSO). This solvatochromic behaviour of NiII-xanthate complex 1 is supplemented by reversible thermochromic behaviour over a wide temperature ca 30-90 degrees C. Notably, thermal degradation of NiII- xanthate complex 1 gave a stable residual mass that corresponds to NiS. The X-band EPR, UV-visible and TD-DFT studies and electrochemical investigations have been performed to rationalize the results and establish the structure-property correlation.

Multi-functional ligand precursors 2-[2-(1-piperazinyl)ethyliminomethyl] phenol (L-1), 1-[2-(1-piperazinyl)ethyliminomethyl]naphthlene-2-ol (L-2) and 6-methoxy-2-[2-(1-piperazinyl)ethyliminomethyl]phenol (L-3) were selected to derive a new series of binuclear and mononuclear M-II-dithiocarbamate complexes of the type [Cu{kappa S-2, S-S2C-piperazine-C2H4N=C(H)(R)}(2)] (2) (R = -Ph(OH) (1), -Naph(OH) (2), -Ph(OH)(OCH3) (3) and [M{kappa S-2,S-S(2)Cpiperazine-C2H4N = C(H)(R)}(2)] (R = -Ph(OH), M = Ni-II 4, Zn-II 5; R = -Naph(OH), M = Ni-II 6, Zn-II 7; R =- Ph(OH) (OCH3), M = Ni-II 8, Zn-II 9). All the compounds have been characterized by microanalysis and standard spectroscopic methods such as H-1 and C-13 NMR, IR and UV-visible absorption spectroscopy. The molecular structures for L-1 and its Cu-II-/Ni-II-dithiocarbamate complexes 1 and 4 were elucidated by single crystal X-ray diffraction (SCXRD) and their crystal packing patterns were studied. Interestingly, molecules of L-1 forms 3D multiple open tubular supramolecular assembly by involving H bonding and other NH center dot center dot center dot O=C, CHbenzene center dot center dot center dot O and CHpiperazine center dot center dot center dot O weak intermolecular forces. Notably, Zn-II-dithiocarabamate complexes give maximum emission in visible nm region (ca 444-489) upon excitation of ultraviolet radiation with concomitant Stock shift ca < 200 nm. Thermogravimetric study was performed on 1-9 to investigate their thermal stability and degradation patterns. All the compounds have been screened for their potential in vitro antimicrobial activity against by using S. aureus, E. coli and C. albicans by Broth dilution method. The density functional theory calculations have been carried out to reinforce the experimental outcomes.

This study presents a novel recycling scheme for spent Li-ion batteries that involves the leaching of lithium in hot water followed by the dissolution of all transition metals in HCl solution and their separation using the ionic liquid Cyphos IL104. The parametric studies revealed that >84 % Li was dissolved while the cathode material was leached at 90 degrees C for 2 h. Approximately 98 % Li from the non-acidic solution was directly precipitated as Li2CO3 at a Li+:CO32- ratio of 1:1.5. The transition metals from the Li-depleted cathode mass were efficiently (>98 %) dissolved in 3.0 mol.L-1 HCl at 90 degrees C for a 3 h leaching process. Manganese from the chloride leach liquor was selectively precipitated by adding KMnO4 at a 1.25-fold higher quantity than the stoichiometric ratio, pH value 2.0, and temperature 80 degrees C. The remaining co-existing metals (Ni and Co) were separated from the chloride solution by contacting it with a phosphonium-based ionic liquid at an equilibrium pH value of 5.4 and an organic-to-aqueous phase ratio of 2/3. The loaded ionic liquid was quantitatively stripped in 2.0 mol.L-1 H2SO4 solution, which yielded high-purity CoSO4 center dot xH(2)O crystals after evaporation of the stripped liquor. Subsequently, similar to 99 % nickel was recovered as nickel carbonate [NiCO3 center dot 2Ni(OH)(2)] from the Co-depleted raffinate by the precipitation performed at Ni2+:CO32- ratio of 1:2.5, pH value of 10.8, and temperature of 50 degrees C. Finally, a process flow with mass and energy balances yielding a high recovery rate of all metals in the exhausted cathode powder of spent LiBs was proposed.

Optically pure enantiomeric pair viz. ferrocene functionalized chiral tertiary amines S,S-(-)-1 and R,R-(+)-2 have been synthesized from ferrocenylmethylamine to probe the influence of chirality and the redox potential on their anti-proliferative activity. Compounds were characterized by microanalysis, HPLC, H-1, C-13 NMR, UV-visible, fluorescence, FTIR, thermogravimetric and crystallographic techniques. The single crystal X-ray diffraction (SCXRD) study revealed that the molecules of 1 holding S,S-chirality at benzylic carbons forms a fascinating M-helix while 2 holding R,R-chirality at benzylic carbons forms P-helix by involving intra- and intermolecular H-bonding interactions as verified by Hirshfeld surface analysis. Chirality-related influence was observed on the antiproliferative activity of enantiomeric pair and at the supramolecular level. For instance, enantiomer R,R-(+)-2 is found to be highly active against all the investigated human carcinoma cell lines MCF 7, IMR 32, HepG2, and immortal L132 cell lines. In particular, R,R-(+)-2 exhibited more than 10 folds better antiproliferation (IC50 : 6.35 +/- 0.19 mu M) than other enantiomer S,S-(-)-1 (IC50 : 65.96 +/- 0.12 mu M) and four folds better activity than highly successful anticancer drug, cisplatin (IC50 : 24.3 +/- 1.7 mu M) against Hep G2 cell line. The electrochemical, DFT calculations and molecular docking study have been performed to justify the experimental outcomes. (C) 2021 Elsevier B.V. All rights reserved.

The present report describes a new series of amide functionalized 20‐ and 30‐aminomethylferrocene derived from ferrocenylmethylamine. The compounds 1a‐5a and 1b‐5b were characterized by microanalysis, 1H, 13C NMR, UV–visible, fluorescence, FTIR, thermogravimetric and crystallographic techniques. The X‐ray analysis demonstrated the ability of these molecules to form various intermolecular hydrogen bonding interactions, as verified by Hirshfeld surface analysis. All the compounds were evaluated against MCF 7, IMR 32, HepG2 and immortal L132 cell lines by MTT assay and the results were compared with cisplatin. Interestingly, many compounds were very active against all the investigated cell lines and proved to be more potent as cytotoxic agents than cisplatin. The western blot, gene expression, mitochondrial membrane potential and flow cytometry study were used to investigate the mode of action of these derivatives as antitumor agents. The results showed apoptotic property of the compounds by modulating inflammatory pathway against human tumor cells of different origin. We performed the density functional theory calculations and molecular docking to rationalize the experimental results.

Diethanol amine (DEA) was selected as a lead compound to prepare N-tosyldiethanol amine 1, N-tosylbis(2-(tosyloxy)ethyl)amine 2 and disubstituted piperazines ca N-alkyl-N′-tosylpiperazines 3–5 in high yield. The new compounds were characterized by using relevant techniques viz. MS, IR, 1H, 13C, DEPT 135 NMR, UV–vis. absorption and fluorescence spectral studies. Single crystal X-ray diffraction technique was used to detect a new polymorphic form of 2 and to measure the influence of various N-substituents on the association of molecules of 3–5 in the solid state. Evidently, the introduction of N-cyclohexyl substituent in 3 successfully switches off all the synthons ca CH…O and CH…N seen in compound 4 and 5. Compounds 4 and 5 holding N-furfuryl and N-benzyl substituents, respectively, adopt other packing strategies based on CH…O, CH…N (4) and CH…O (5) interactions. The antitumor activity of 1–5 was evaluated in vitro against Hep 3B and IMR 32 by the MTT assay and the results were compared with cisplatin. Remarkably, some compounds were found extremely active against both the cell lines and proved to be more potent as cytotoxic agents than cisplatin. Density functional theory and molecular docking studies have been performed to rationalize the experimental results.