Structure‐Based Design of Platinum(II) Complexes as c‐myc Oncogene Down‐Regulators and Luminescent Probes for G‐Quadruplex DNA

A series of platinum(II) complexes with tridentate ligands was synthesized and their interactions with G‐quadruplex DNA within the c‐myc gene promoter were evaluated. Complex 1 , which has a flat planar 2,6‐bis(benzimidazol‐2‐yl)pyridine (bzimpy) scaffold, was found to stabilize the c‐myc G‐quadruplex structure in a cell‐free system. An in silico G‐quadruplex DNA model has been constructed for structure‐based virtual screening to develop new Pt^II‐based complexes with superior inhibitory activities. By using complex 1 as the initial structure for hit‐to‐lead optimization, bzimpy and related 2,6‐bis(pyrazol‐3‐yl)pyridine (dPzPy) scaffolds containing amine side‐chains emerge as the top candidates. Six of the top‐scoring complexes were synthesized and their interactions with c‐myc G‐quadruplex DNA have been investigated. The results revealed that all of the complexes have the ability to stabilize the c‐myc G‐quadruplex. Complex 3 a ([Pt^II L2R ] ⁺ ; L2 =2,6‐bis[1‐(3‐piperidinepropyl)‐1H‐enzo[d]imidazol‐2‐yl]pyridine, R =Cl) displayed the strongest inhibition in a cell‐free system (IC₅₀=2.2 μM ) and was 3.3‐fold more potent than that of 1 . Complexes 3 a and 4 a ([Pt^II L3R ]⁺; L3 =2,6‐bis[1‐(3‐morpholinopropyl)‐1H‐pyrazol‐3‐yl]pyridine, R =Cl) were found to effectively inhibit c‐myc gene expression in human hepatocarcinoma cells with IC₅₀ values of ≈17 μM , whereas initial hit 1 displayed no significant effect on gene expression at concentrations up to 50 μM . Complexes 3 a and 4 a have a strong preference for G‐quadruplex DNA over duplex DNA, as revealed by competition dialysis experiments and absorption titration; 3 a and 4 a bind G‐quadruplex DNA with binding constants (K) of approximately 10⁶–10⁷ dm³ mol^?1, which are at least an order of magnitude higher than the K values for duplex DNA. NMR spectroscopic titration experiments and molecular modeling showed that 4 a binds c‐myc G‐quadruplex DNA through an external end‐stacking mode at the 3′‐terminal face of the G‐quadruplex. Intriguingly, binding of c‐myc G‐quadruplex DNA by 3 b is accompanied by an increase of up to 38‐fold in photoluminescence intensity at λ_max=622 nm.     

Two Lanthanide(III) Complexes based on the Schiff Base N,N′‐Bis(salicylidene)‐1,5‐diamino‐3‐oxapentane: Synthesis,Characterization, DNA‐binding Properties,and Antioxidation

The Schiff base N,N′‐bis(salicylidene)‐1,5‐diamino‐3‐oxapentane (H₂L) and its lanthanide(III) complexes, PrL(NO₃)(DMF)(H₂O) ( 1 ) and Ho₂L₂(NO₃)₂ · 2H₂O ( 2 ), were synthesized and characterized by physicochemical and spectroscopic methods. Single crystal X‐ray structure analysis revealed that complex 1 is a discrete mononuclear species. The Pr^III ion is nine‐coordinate, forming a distorted capped square antiprismatic arrangement. Complex 2 is a centrosymmetric dinuclear neutral entity in which the Ho^III ion is eight‐coordinate with distorted square antiprismatic arrangement. The DNA‐binding properties of H₂L and its Ln^III complexes were investigated by spectrophotometric methods and viscosity measurements. The results suggest that the ligand H₂L and its Ln^III complexes both connect to DNA in a groove binding mode; the complexes bind more strongly to DNA than the ligand. Moreover, the antioxidant activities of the Ln^III complexes were in vitro determined by superoxide and hydroxyl radical scavenging methods, which indicate that complexes 1 and 2 have OH ^· and O₂^{– ·} radical scavenging activity.     

Effect of Heavy‐Atom (Br) at the Phenyl Rings of Schiff‐Base Ligands on the NIR Luminescence of their Bimetallic Zn‐Nd Complexes

Two heterobimetallic Zn‐Nd phenylene‐bridged Schiff‐base ligands complexes [ZnNd L¹ (Py)(NO₃)₃] ( 1 ) and [Zn L² Nd(Py)(NO₃)₃]·MeCN ( 2 ) (Py = pyridine, H₂L¹ = N,N′‐bis‐ (3‐methoxy‐salicylidene)phenylene‐1,2‐diamine, H₂L² = N,N′‐bis‐5‐bromo‐3‐methoxy‐salicylidene)phenylene‐1,2‐diamine) were obtained. Both 1 and 2 were structurally characterized by X‐ray crystallography, and their near‐infrared (NIR) luminescent properties were determined. For the two complexes, the occupation of pyridine at the axial position of 3d Zn²⁺ ions could effectively prevent luminescent quenching arising from OH‐, NH‐ or CH oscillators of the solvates around the 4f Nd³⁺ ions, and the heavy‐atom (Br) effect of the Schiff‐base ligands on their NIR luminescent properties is also discussed.     

Solution Structure of a G‐quadruplex Bound to the Bisquinolinium Compound Phen‐DC3

Phen‐DC₃ is a highly promising compound that specifically targets G‐quadruplexes, with potent biological effects observed in vivo. We used NMR spectroscopy to solve the structure of the complex formed between Phen‐DC₃ and an intramolecular G‐quadruplex derived from the c‐myc promoter. Structural information revealed that Phen‐DC₃ interacts with the quadruplex through extensive π‐stacking with guanine bases of the top G‐tetrad. On the basis of our structure, modifications are proposed for the development of this compound for selective targeting of a specific G‐quadruplex conformation.     

Template‐Assembled Synthetic G‐Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies

A new biomolecular device for investigating the interactions of ligands with constrained DNA quadruplex topologies, using surface plasmon resonance (SPR), is reported. Biomolecular systems containing an intermolecular‐like G‐quadruplex motif 1 (parallel G‐quadruplex conformation), an intramolecular G‐quadruplex 2 , and a duplex DNA 3 have been designed and developed. The method is based on the concept of template‐assembled synthetic G‐quadruplex (TASQ), whereby quadruplex DNA structures are assembled on a template that allows precise control of the parallel G‐quadruplex conformation. Various known G‐quadruplex ligands have been used to investigate the affinities of ligands for intermolecular 1 and intramolecular 2 DNA quadruplexes. As anticipated, ligands displaying a π‐stacking binding mode showed a higher binding affinity for intermolecular‐like G‐quadruplexes 1 , whereas ligands with other binding modes (groove and/or loop binding) showed no significant difference in their binding affinities for the two quadruplexes 1 or 2 . In addition, the present method has also provided information about the selectivity of ligands for G‐quadruplex DNA over the duplex DNA. A numerical parameter, termed the G‐quadruplex binding mode index (G4‐BMI), has been introduced to express the difference in the affinities of ligands for intermolecular G‐quadruplex 1 against intramolecular G‐quadruplex 2 . The G‐quadruplex binding mode index (G4‐BMI) of a ligand is defined as follows: G4‐BMI=K_D^intra/K_D^inter, where K_D^intra is the dissociation constant for intramolecular G‐quadruplex 2 and K_D^inter is the dissociation constant for intermolecular G‐quadruplex 1 . In summary, the present work has demonstrated that the use of parallel‐constrained quadruplex topology provides more precise information about the binding modes of ligands.     

Photo‐Cross‐Linking Probes for Trapping G‐Quadruplex DNA

We have developed a straightforward synthetic pathway to a set of six photoactivatable G‐quadruplex ligands with a validated G4‐binding motif (the bisquinolinium pyridodicarboxamide PDC‐360A) tethered through various spacers to two different photo‐cross‐linking groups: benzophenone and an aryl azide. The high quadruplex‐versus‐duplex selectivity of the PDC core was retained in the new derivatives and resulted in selective alkylation of two well‐known G‐quadruplexes (human telomeric G4 and oncogene promoter c‐myc G4) under conditions of harsh competition. The presence of two structurally different photoactivatable functions allowed the selective alkylation of G‐quadruplex structures at specific nucleobases and irreversible G4 binding. The topology and sequence of the quadruplex matrix appear to influence strongly the alkylation profile, which differs for the telomeric and c‐myc quadruplexes. The new compounds are photoactive in cells and thus provide new tools for studying G4 biology.     

Effect of the Ancillary Ligands on the Spectral Properties and G‐Quadruplexes DNA Binding Behavior: A Combined Experimental and Theoretical Study

In an effort to explore the effect of ancillary ligands on the spectral properties and overall G‐quadruplex DNA binding behavior, two new ruthenium(II) complexes [Ru(phen)₂(dppzi)]²⁺ ( 1 ) and [Ru(dmp)₂(dppzi)]²⁺ ( 2 ) (phen=1,10‐phenanthroline, dmp=2,9‐dimethyl‐1,10‐phenanthroline, dppzi=dipyrido[3,2‐a:2′,3′‐c]phenazine‐10,11‐imidazole) were prepared. Complex 1 can emit luminescence in the absence and presence of G‐quadruplexes DNA. However, with ?CH₃ substituent on the 2‐ and 9‐positions of the phen ancillary ligand, no detectable luminescence is observed for complex 2 in any organic solvent or in the absence and/or presence of G‐quadruplex DNA. Experimental and molecular docking studies indicated that both complexes interacted with the human telomeric repeat AG3(T2AG3)3 (22AG) G‐quadruplex with the stoichiometric ratio of 1:1, but the two complexes showed different G‐quadruplex DNA binding affinity. Complex 1 binds to the G‐quadruplexes DNA more tightly than complex 2 does. Our results demonstrate that methyl groups on the phen ancillary ligand significantly affect the spectral properties and the overall DNA binding behavior of the complexes. Such difference in spectral properties and DNA binding affinities of these two complexes can be reasonably explained by DFT/TD‐DFT calculations. This work provides guidance not only on exploring the G‐quadruplexes DNA binding behavior of complexes, but also understanding the unique luminescence mechanism.     

The Synthesis and Characterization of s‐Triazine‐Cored Tripodal Structure and Its Salen/Salophen‐Bridged Fe/Cr(III) Capped Complexes

A novel Schiff base compound was synthesized, and its complexation properties with Fe(III) and Cr(III) were investigated. Tripodal ligand was synthesized by the reaction of s‐triazine and 4‐hydroxybenzaldehyde. Then a Schiff base involving 8‐hydroxyquinoline was synthesized by the reaction of 5‐aminomethyl‐8‐hydroxyquinoline ( QN ) and 2,4,6‐tris(p‐formylphenoxy)‐1,3,5‐triazine ( TRIPOD ) in methanol/chloroform media. The obtained Schiff base ( QN-TRIPOD ) was then reacted with four trinuclear Fe(III) and Cr(III) complexes including tetradentate Schiff bases N ,N ′‐bis(salicylidene)ethylenediamine (salenH₂)/bis(salicylidene)‐o‐phenylenediamine (SalophenH₂). The synthesized ligand and complexes were characterized by means of elemental analysis carrying out ¹H NMR, FTIR spectroscopy, thermal analyses, and magnetic susceptibility measurements. Finally, metal ratios of the prepared complexes were determined by using atomic adsorption spectrometry.     

Synthesis and crystal structure of the dinuclear copper(II) Schiff base complex μ‐hydroxido‐μ‐chlorido‐bis{[bis(trans‐2‐nitrocinnamaldehyde)ethylenediamine]chloridocopper(II)} dichloromethane sesquisolvate

Transition metal complexes of Schiff base ligands have been shown to have particular application in catalysis and magnetism. The chemistry of copper complexes is of interest owing to their importance in biological and industrial processes. The reaction of copper(I) chloride with the bidentate Schiff base N,N′‐bis(trans‐2‐nitrocinnamaldehyde)ethylenediamine {Nca₂en, systematic name: (1E,1′E,2E,2′E)‐N,N′‐(ethane‐1,2‐diyl)bis[3‐(2‐nitrophenyl)prop‐2‐en‐1‐imine]} in a 1:1 molar ratio in dichloromethane without exclusion of air or moisture resulted in the formation of the title complex μ‐chlorido‐μ‐hydroxido‐bis(chlorido{(1E,1′E,2E,2′E)‐N,N′‐(ethane‐1,2‐diyl)bis[3‐(2‐nitrophenyl)prop‐2‐en‐1‐imine]‐κ²N,N′}copper(II)) dichloromethane sesquisolvate, [Cu₂Cl₃(OH)(C₂₀H₁₈N₄O₄)₂]·1.5CH₂Cl₂. The dinuclear complex has a folded four‐membered ring in an unsymmetrical Cu₂OCl₃ core in which the approximate trigonal bipyramidal coordination displays different angular distortions in the equatorial planes of the two Cu^II atoms; the chloride bridge is asymmetric, but the hydroxide bridge is symmetric. The chelate rings of the two Nca₂en ligands have different conformations, leading to a more marked bowing of one of the ligands compared with the other. This is the first reported dinuclear complex, and the first five‐coordinate complex, of the Nca₂en Schiff base ligand. Molecules of the dimer are associated in pairs by ring‐stacking interactions supported by C—H…Cl interactions with solvent molecules; a further ring‐stacking interaction exists between the two Schiff base ligands of each molecule.     

Assembly of Palladium(II) and Platinum(II) Metallo‐Rectangles with a Guanosine‐Substituted Terpyridine and Study of Their Interactions with Quadruplex DNA

Two novel [2+2] metallo‐assemblies based on a guanosine‐substituted terpyridine ligand ( 1 ) coordinated to palladium(II) ( 2 a ) and platinum(II) ( 2 b ) are reported. These supramolecular assemblies have been fully characterized by NMR spectroscopy, ESI mass spectrometry and elemental analyses. The palladium(II) complex ( 2 a ) has also been characterized by single crystal X‐ray diffraction studies confirming that the system is a [2+2] metallo‐rectangle in the solid state. The stabilities of these [2+2] assemblies in solution have been confirmed by DOSY studies as well as by variable temperature ¹H NMR spectroscopy. The ability of these dinuclear complexes to interact with quadruplex and duplex DNA was investigated by fluorescent intercalator displacement (FID) assays, fluorescence resonance energy transfer (FRET) melting studies, and electrospray mass spectrometry (ESI‐MS). These studies have shown that both these assemblies interact selectively with quadruplex DNA (human telomeric DNA and the G‐rich promoter region of c‐myc oncogene) over duplex DNA, and are able to induce dimerization of parallel G‐quadruplex structures.     

A simple one pot synthesis of condensed 1,2,4‐triazines by using the tandem aN‐SNipso and SNH‐SNipsa reactions

A new synthetic approach to condensed 1,2,4‐triazines based on using the tandem A_N‐S_N^ipso and S_N^H‐S_N^ipso reactions has been developed. 5‐Methoxy‐3‐penyl‐1,2,4‐triazine and its N₁‐methyl quaternary salt were found to react with C,N‐, C,O‐ and N,N'‐bifunctional nucleophiles (m‐phenylenediamine, resor‐cinol, semicarbazide and ureas) into triazacarbazoles, benzofuro[2,3‐e][1,2,4]‐triazines, and 6‐azapurine derivatives. In all cases nucleophiles attack first the unsubstituted C‐6 carbon of the triazine ring, while the final stage is replacement of the methoxy group affording cyclization products.     

Thermal reactions of N‐alkyl‐2‐benzylaniline and N‐alkyl‐N′‐phenyl‐o‐phenylenediamine: An unusual route to 2‐phenylindole and 2‐phenylbenzimidazole

Thermal cyclization reactions of N‐alkyl‐2‐benzylaniline 1a‐d and N‐alkyl‐N′‐phenyl‐o‐phenylenediamine 2a‐b were carried out expecting to get seven‐membered heterocyclic compounds. However, the results show that aside from the formation of the normally expected six‐membered ring products of acridine 5 , anthracene 6 , and phenazine 8 , thermal cyclization of N‐alkyl‐2‐benzylaniline and N‐alkyl‐N′‐phenyl‐o‐phenylenediamine also resulted to the unexpected formation of 2‐phenylindole 3 and 2,3‐diphenylindole 4 , and 2‐phenylbenzimidazole 7 , respectively.     

Cationic Pentaheteroaryls as Selective G‐Quadruplex Ligands by Solvent‐Free Microwave‐Assisted Synthesis

We report herein a solvent‐free and microwaved‐assisted synthesis of several water soluble acyclic pentaheteroaryls containing 1,2,4‐oxadiazole moieties ( 1 – 7 ). Their binding interactions with DNA quadruplex structures were thoroughly investigated by FRET melting, fluorescent intercalator displacement assay (G4‐FID) and CD spectroscopy. Among the G‐quadruplexes considered, attention was focused on telomeric repeats together with the proto‐oncogenic c‐kit sequences and the c‐myc oncogene promoter. Compound 1 , and to a lesser extent 2 and 5 , preferentially stabilise an antiparallel structure of the telomeric DNA motif, and exhibit an opposite binding behaviour to structurally related polyoxazole ( TOxaPy ), and do not bind duplex DNA. The efficiency and selectivity of the binding process was remarkably controlled by the structure of the solubilising moieties.     

Five related N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamides

In the solid state, 4‐methoxy‐N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamide, C₁₀H₁₀Cl₃N₃O, (I), N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamide, C₉H₈Cl₃N₃, (II), 4‐chloro‐N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamide, C₉H₇Cl₄N₃, (III), 4‐bromo‐N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamide, C₉H₇BrCl₃N₃, (IV), and 4‐trifluoromethyl‐N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamide, C₁₀H₇Cl₃F₃N₃, (V), display strong intramolecular N—H...N hydrogen bonding across the chelate ring and also intramolecular N—H...Cl contacts. Additional intermolecular hydrogen bonds link the molecules into chains, double chains or sheets in all cases except for compound (V). For compound (II), there are three independent molecules per asymmetric unit.     

Mononuclear and three‐dimensional metal complexes based on a multidentate hydrazone ligand

A potentially pentadentate hydrazone ligand, N′‐[1‐(pyrazin‐2‐yl)ethylidene]nicotinohydrazide (HL), was prepared from the condensation reaction of nicotinohydrazide and acetylpyrazine. Reactions of HL with MnCl₂, Mn(CH₃COO)₂ and Cd(CH₃COO)₂ afforded three metal complexes, namely dichlorido{N′‐[1‐(pyrazin‐2‐yl‐κN¹)ethylidene]nicotinohydrazide‐κ²N′,O}manganese(II), [MnCl₂(C₁₂H₁₁N₅O)], (I), bis{N′‐[1‐(pyrazin‐2‐yl‐κN¹)ethylidene]nicotinohydrazidato‐κ²N′,O]manganese(II), [Mn(C₁₂H₁₀N₅O)₂], (II), and poly[[(acetato‐κ²O,O′){μ₃‐N′‐[1‐(pyrazin‐2‐yl‐κ²N¹:N⁴)ethylidene]nicotinohydrazidato‐κ³N′,O:N¹}cadmium(II)] chloroform disolvate], {[Cd(C₁₂H₁₀N₅O)(CH₃COO)]·2CHCl₃}_n, (III), respectively. Complex (I) has a mononuclear structure, the Mn^II centre adopting a distorted square‐pyramidal coordination. Complex (II) also has a mononuclear structure, with the Mn^II centre occupying a special position (C₂ symmetry) and adopting a distorted octahedral coordination environment, which is defined by two O atoms and four N atoms from two N′‐[1‐(pyrazin‐2‐yl)ethylidene]nicotinohydrazidate (L⁻) ligands related via a crystallographic twofold axis. Complex (III) features a unique three‐dimensional network with rectangular channels, and the L⁻ ligand also serves as a counter‐anion. The coordination geometry of the Cd^II centre is pentagonal bipyramidal. This study demonstrates that HL, which can act as either a neutral or a mono‐anionic ligand, is useful in the construction of interesting metal–organic compounds.     

Stabilization of Human Telomeric G‐Quadruplex and Inhibition of Telomerase Activity by Propeller‐Shaped Trinuclear PtII Complexes

Two novel propeller‐shaped, trigeminal‐ligand‐containing, flexible trinuclear Pt^II complexes, {[Pt(dien)]₃(ptp)}(NO₃)₆ ( 1 ) and {[Pt(dpa)]₃(ptp)}(NO₃)₆ ( 2 ) (dien: diethylenetriamine; dpa: bis‐(2‐pyridylmethyl)amine; ptp: 6′‐(pyridin‐3‐yl)‐3,2′:4′,3′′‐terpyridine), have been designed and synthesized, and their interactions with G‐quadruplex (G4) sequences are characterized. A combination of biophysical and biochemical assays reveals that both Pt^II complexes exhibit higher affinity for human telomeric (hTel) and c‐myc promoter G4 sequences than duplex DNA. Complex 1 binds and stabilizes hTel G4 sequence more effectively than complex 2 . Both complexes are found to induce and stabilize either antiparallel or parallel conformation of G4 structures. Molecular docking studies indicate that complex 1 binds into the large groove of the antiparallel hTel G4 structure (PDB ID: 143D) and complex 2 stacks onto the exposed G‐quartet of the parallel hTel G4 structure (PDB ID: 1KF1). Telomeric repeat amplification protocol assays demonstrate that both complexes are good telomerase inhibitors, with IC₅₀ values of (16.0±0.4) μM and (4.20±0.25) μM for 1 and 2 , respectively. Collectively, the results suggest that these propeller‐shaped flexible trinuclear Pt^II complexes are effective and selective G4 binders and good telomerase inhibitors. This work provides valuable information for the interaction between multinuclear metal complexes with G4 DNA.     

Bis{1‐[N‐(2‐methoxy­phenyl)imino­methyl]naphthalen‐2(1H)‐onato‐κ3O,N,O′}zinc(II) ethanol solvate

In the crystal structure of the title compound, [Zn(C₁₈H₁₄NO₂)₂]·C₂H₆O, the Zn atom displays a highly distorted octa­hedral coordination involving the O and N atoms of two mol­ecules of the Schiff base 1‐[N‐(2‐methoxy­phenyl)imino­methyl]naphthalen‐2(1H)‐one, which acts as an O,N,O′‐tridentate ligand. The ethanol mol­ecule is bound to the methoxy group of one ligand mol­ecule via a hydrogen bond.     

Polycyclic Azoniahetarenes: Assessing the Binding Parameters of Complexes between Unsubstituted Ligands and G‐Quadruplex DNA

Polycyclic azoniahetarenes were employed to determine the effect of the structure of unsubstituted polyaromatic ligands on their quadruplex‐DNA binding properties. The interactions of three isomeric diazoniadibenzo[b,k]chrysenes ( 4 a – c ), diazoniapentaphene ( 5 ), diazoniaanthra[1,2‐a]anthracene ( 6 ), and tetraazoniapentapheno[6,7‐h]pentaphene ( 3 ) with quadruplex DNA were examined by DNA melting studies (FRET melting) and fluorimetric titrations. In general, penta‐ and hexacyclic azoniahetarenes bind to quadruplex DNA (K_b≈10⁶ M ^?1) even in the absence of additional functional side chains. The binding modes of 4 a – c and 3 were studied in more detail by ligand displacement experiments, isothermal titration calorimetry, and CD and NMR spectroscopy. All experimental data indicate that terminal π stacking of the diazoniachrysenes to the quadruplex is the major binding mode; however, because of different electron distributions of the π systems of each isomer, these ligands align differently in the binding site to achieve ideal binding interactions. It is proposed that tetraazonia ligand 3 binds to the quadruplex by terminal stacking with a small portion of its π system, whereas a significant part of the bulky ligand most likely points outside the quadruplex structure, and is thus partially placed in the grooves. Notably, 3 and the known tetracationic porphyrin TMPyP4 exhibit almost the same binding properties towards quadruplex DNA, with 3 being more selective for quadruplex than for duplex DNA. Overall, studies on azonia‐type hetarenes enable understanding of some parameters that govern the quadruplex‐binding properties of parent ligand systems. Since unsubstituted ligands were employed in this study, complementary and cooperative effects of additional substituents, which may interfere with the ligand properties, were eliminated.     

The reaction of 3,4‐diamino‐1,2,5‐oxadiazoles with formaldehyde

The compounds 5,6‐dihydro‐4H‐imidazo[4,5‐c][1,2,5]oxadiazole ( 3a , R?H), 4,6,10,12‐tetramethyl‐5,6,11,12‐tetrahydro‐4H,10H‐bis(1,2,5)oxadiazolo[3,4‐d:3′,4′‐I][1,3,6,8]tetraazecine ( 4b , R?CH₃), N³,N³′‐methylenebis‐3,4‐diamino‐1,2,5‐oxadiazole ( 5a , R?H) and N³,N³′‐methylenebis(N,N′‐dimethyl‐3,4‐diamino‐1,2,5‐oxadiazolee) ( 5b , R?CH₃) were synthesized from the reaction of formaldehyde with 3,4‐diamino‐1,2,5‐oxadiazole and N,N′‐3,4‐dimethylamino‐1,2,5‐oxadiazole in an acetonitrile.     

Synthesis,characterization and crystal structures of the bidentate Schiff base N,N′‐bis(2‐nitrocinnamaldehyde)ethylenediamine and its complex with CuNCS and triphenylphosphane

Reaction of copper(I) thiocyanate and triphenylphosphane with the bidentate Schiff base N,N′‐bis(trans‐2‐nitrocinnamaldehyde)ethylenediamine {Nca₂en, (1); systematic name (1E,1′E,2E,2′E)‐N,N′‐(ethane‐1,2‐diyl)bis[3‐(2‐nitrophenyl)prop‐2‐en‐1‐imine]}, C₂₀H₁₈N₄O₄, in a 1:1:1 molar ratio in acetonitrile resulted in the formation of the complex {(1E,1′E,2E,2′E)‐N,N′‐(ethane‐1,2‐diyl)bis[3‐(2‐nitrophenyl)prop‐2‐en‐1‐imine]‐κ²N,N′}(thiocyanato‐κN)(triphenylphosphane‐κP)copper(I)], [Cu(NCS)(C₂₀H₁₈N₄O₄)(C₁₈H₁₅P)] or [Cu(NCS)(Nca₂en)(PPh₃)], (2). The Schiff base and copper(I) complex have been characterized by elemental analyses, IR, electronic and ¹H NMR spectroscopy, and X‐ray crystallography [from synchrotron data for (1)]. The molecule of (1) lies on a crystallographic inversion centre, with a trans conformation for the ethylenediamine unit, and displays significant twists from coplanarity of its nitro group, aromatic ring, conjugated chain and especially ethylenediamine segments. It acts as a bidentate ligand coordinating via the imine N atoms to the Cu^I atom in complex (2), in which the ethylenediamine unit necessarily adopts a somewhat flattened gauche conformation, resulting in a rather bowed shape overall for the ligand. The NCS⁻ ligand is coordinated through its N atom. The geometry around the Cu^I atom is distorted tetrahedral, with a small N—Cu—N bite angle of 81.56 (12)° and an enlarged opposite angle of 117.29 (9)° for SCN—Cu—P. Comparisons are made with the analogous Schiff base having no nitro substituents and with metal complexes of both ligands.