Diamine Backbone Research Articles

Synthesis, Characterisation, in vitro antibacterial and in silico docking studies of Schiff bases of p-nitro benzaldehyde

Schiff base ligands have more pharamaceutical applications and are widely used in pharmaceutical industries. Herein, two kinds of Schiff base ligands were synthesized using p-nitrobenzaldehyde with (L1) 1H-1,2,4-triazol-3-amine and (L2) 1,4 phenylene diamine backbone. Synthesised ligands were characterized utilizing ultraviolet visible spectroscopy, Fourier Transform Infra-red Spectroscopy, Carbon 13C NMR and Proton 1H. Then in vitro antimicrobial activity, PASS analysis, Drug likeness and in silico docking studies of synthesized ligands (L1 and L2) were carried out. With the help of PASS and bioactive score results, docking studies were done using two different proteins (PDB ID:6D9T and PDB ID:6HZQ) by Auto dock 4.2.6 program. BNBBDA has good affinity with target protein S. aureus (PDB ID:6D9T) and PNBTAA has with protein E.coli (PDB ID:6HZQ). The findings demonstrated that the compounds are the ideal candidates for the subsequent steps of drug discovery.

Ring-Opening Co- and Terpolymerization of Epoxides, Cyclic Anhydrides, and l-Lactide Using Constrained Aluminum Inden Complexes.

Seven constrained aluminum inden complexes having different substituents and diamine backbones were developed for the ring-opening copolymerization (ROCOP) of epoxides and bulky cyclic anhydrides giving alternating polyesters with Tg ranging from 49 to 226 °C. Among several catalyst/cocatalyst screenings, the aluminum inden complex having a rigid phenylene backbone coupled with 4-dimethylaminopyridine showed the best performance giving linear polyesters. In the case of cyclohexene oxide (CHO) and succinic anhydride (SA), the linear poly(CHO-alt-SA) could be transformed to cyclic polymer when the polymerization was left under prolonged reaction time to induce intramolecular transesterification. The kinetic studies of the ROCOP revealed a zeroth-order dependence on cyclic anhydride and a first-order dependence on epoxide and the catalyst. The catalysts can be extended efficiently to the one-pot CHO/PA/l-lactide terpolymerization giving uncommon tapered copolymers of poly(CHO-alt-PA) and PLA via switchable polymerization.

Cyclic Carbonate Synthesis from Epoxides and CO2 Catalyzed by Aluminum-Salen Complexes Bearing a nido-C2B9 Carborane Ligand.

The active and well-designed Schiff base ligands are considered "privileged ligands". The so-called salen ligands, i.e., the tetradentate [O, N, N, O] bis-Schiff base ligands, have also found broad applications in many homogeneous catalytic reactions. Modification of the salen ligands has concentrated on altering the substituents in the phenolate rings and variations in the diamine backbones. Herein, o-carborane-supported salen ligands (2) were designed and prepared. A series of aluminum-salen complexes (3·(sol)2), which were supported by the nido-C2B9 carborane anions, were synthesized. These Al(III) complexes showed high activities (TOF up to 1500 h-1) in catalyzing the cycloaddition of epoxides and CO2 at atmospheric pressure and near room temperature. Complexes 3·(sol)2 are one of the rare examples of Al-based catalysts capable of promoting cycloaddition at 1 bar pressure of CO2. Density functional theory (DFT) studies combined with the catalytic results reveal that the catalytic cycles occur on two axial sites of the Al(III) center.

Bis(amido)bis(oxinate)diamine Ligands for theranostic radiometals

With the interest in radiometal-containing diagnostic and therapeutic pharmaceuticals increasing rapidly, appropriate ligands to coordinate completely and stably said radiometals is essential. Reported here are two novel, bis(amido)bis(oxinate)diamine ligands, H2amidohox (2,2′-(ethane-1,2-diylbis(((8-hydroxyquinolin-2-yl)methyl)azanediyl))diacetamide) and H2amidoC3hox (2,2′-(propane-1,3-diylbis(((8-hydroxyquinolin-2-yl)methyl)azanediyl))diacetamide), that combine two 8-hydroxyquinoline and amide donor groups and differ by one carbon in their 1,2-ethylenediamine vs. 1,3-diaminopropane backbones, respectively. Both ligands have been thoroughly studied via metal complexation, solution thermodynamics and radiolabeling with three radiometal ions: [nat/64Cu]Cu2+, [nat/111In]In3+, and [nat/203Pb]Pb2+. X-ray crystallography determined the structures of the hexacoordinated Cu2+-ligand complexes, indicating a better fit of Cu2+ to the H2amidohox binding pocket. Concentration dependent radiolabeling with [64Cu]Cu2+ was successfully quantitative as low as 1 μM with H2amidohox and 10 μM with H2amidoC3hox within 5 min at room temperature. However, [64Cu][Cu(amidohox)] maintained higher kinetic inertness against a superoxide dismutase enzyme-challenge assay and ligand challenges compared to the [64Cu][Cu(amidoC3hox)] counterpart. Similarly, H2amidohox had significantly higher radiochemical conversion with both [111In]In3+ (97% at 1 μM) and [203Pb]Pb2+ (97% at 100 μM) under mild conditions compared to H2amidoC3hox (76% with [111In]In3+ at 1 μM and 0% with [203Pb]Pb2+). By studying non-radioactive and radioactive complexation with both ligands, a comprehensive understanding of the coordination differences between two- and three‑carbon diamine backbones is discussed. Overall, the ethylenediamine backbone of H2amidohox proves to be superior in rapid, mild radiolabeling and kinetic inertness towards competing ligands and proteins.

A Ligand-Based Approach to Lead Optimization of N, Nʹ-Substituted Diamines for Leishmanicidal Activity

Several N, N-substituted diamines such as putrescine and N-monoalkylated derivatives have demonstrated potential as lead compounds against Leishmania donovani at submicromolar levels. There is a need to refine available diamines for enhanced leishmanicidal activity. A 3D-QSAR by Comparative molecular field analysis (CoMFA) on a series of tested diamines for their activities against L. donovani was conducted to understand better the mechanism of action and SARs of the compounds. The model was constructed with AM1 energy minimized conformers of the training set compounds (n=20) by the PLS algorithm method, cross-validated by the method of leave-one-out (LOO), and externally validated using the test set compounds (n=5). A robust model with high predictability of untested compounds was obtained for 2PC (latent variables). The coefficients of determinations for PLS regression R2, internal cross-validation, Q2 and external prediction P2 were 0.97 (SDEC=0.095), 0.82 (SDEP=0.102) and 0.73 (SDEP=0.115) respectively with F-value 618.8 for 2PC. The model coefficients graphically translated into contour maps showed regions where steric (62 %) and electrostatic (38 %) properties influence the leishmanicidal activity of the compounds. In addition to the optimum chain length (n=4), a steric effect at position 4 alone or combined with the electrostatic effect at position 3 of the diamine backbone significantly enhanced the leishmanicidal activity. It could further be explored for even higher activity. The model supported the empirical data, which identified N, N'-substituted diamine as the scaffold for leishmanicidal activities and further provided insights for further optimization of the lead compound.

Asymmetric Epoxidation of Olefins Catalyzed by Substituted Aminobenzimidazole Manganese Complexes Derived from L‐Proline

AbstractA family of manganese complexes [Mn(Rpeb)(OTf)2] (peb=1‐(1‐ethyl‐1H‐benzo[d]imidazol‐2‐yl)‐N‐((1‐((1‐ethyl‐1H‐benzo[d]imidazol‐2‐yl)methyl) pyrrolidin‐2‐yl)methyl)‐N‐methylmethanamine)) derived from L‐proline has been synthesized and characterized, where R refers to the group at the diamine backbone. X‐ray crystallographic analyses indicate that all the manganese complexes [Mn(Rpeb)(OTf)2] exhibit cis‐α topology. These types of complexes are shown to catalyze the asymmetric epoxidation of olefins employing H2O2 as a terminal oxidant with up to 96% ee. Obviously, the R group of the diamine backbone can influence the catalytic activity and enantioselectivity in the asymmetric epoxidation of olefins. In particular, Mn(i‐Prpeb)(OTf)2 bearing an isopropyl arm, cannot catalyze the epoxidation reaction with H2O2 as the oxidant. However, when PhI(OAc)2 is used as the oxidant instead, all the manganese complexes including Mn(i‐Prpeb)(OTf)2 can promote the epoxidation reactions efficiently. Taken together, these results indicate that isopropyl substitution on the Rpeb ligand inhibits the formation of active Mn(V)‐oxo species in the H2O2/carboxylic acid system via an acid‐assisted pathway.magnified image

Mechanistic Studies Inform Design of Improved Ti(salen) Catalysts for Enantioselective [3 + 2] Cycloaddition.

Ti(salen) complexes catalyze the asymmetric [3 + 2] cycloaddition of cyclopropyl ketones with alkenes. While high enantioselectivities are achieved with electron-rich alkenes, electron-deficient alkenes are less selective. Herein, we describe mechanistic studies to understand the origins of catalyst and substrate trends in an effort to identify a more general catalyst. Density functional theory (DFT) calculations of the selectivity determining transition state revealed the origin of stereochemical control to be catalyst distortion, which is largely influenced by the chiral backbone and adamantyl groups on the salicylaldehyde moieties. While substitution of the adamantyl groups was detrimental to the enantioselectivity, mechanistic information guided the development of a set of eight new Ti(salen) catalysts with modified diamine backbones. These catalysts were evaluated with four electron-deficient alkenes to develop a three-parameter statistical model relating enantioselectivity to physical organic parameters. This statistical model is capable of quantitative prediction of enantioselectivity with structurally diverse alkenes. These mechanistic insights assisted the discovery of a new Ti(salen) catalyst, which substantially expanded the reaction scope and significantly improved the enantioselectivity of synthetically interesting building blocks.

Enantioselective Resolution Copolymerization of Racemic Epoxides and Anhydrides: Efficient Approach for Stereoregular Polyesters and Chiral Epoxides.

Herein we report an efficient strategy for preparing isotactic polyesters and chiral epoxides via enantioselective resolution copolymerization of racemic terminal epoxides with anhydrides, mediated by enantiopure bimetallic complexes in conjunction with a nucleophilic cocatalyst. The chirality of both the axial linker and the diamine backbones of the ligand are responsible for the chiral induction of this kinetic resolution copolymerization process. The catalyst systems exhibit exceptional levels of enantioselectivity with a kinetic resolution coefficient exceeding 300 for various racemic epoxides, affording highly isotactic copolymers (selectivity factors of more than 300) with a completely alternating structure and low polydispersity index. Most of the produced isotactic polyesters are typical semicrystalline materials with melting temperatures in the range from 77 to 160 °C.

Al(Salen) Metal Complexes in Stereoselective Catalysis.

Salen ligands are a class of Schiff bases simply obtained through condensation of two molecules of a hydroxyl-substituted aryl aldehyde with an achiral or chiral diamine. The prototype salen, or N,N′-bis(salicylidene)ethylenediamine has a long history, as it was first reported in 1889, and immediately, some of its metal complexes were also described. Now, the salen ligands are a class of N,N,O,O tetradentate Schiff bases capable of coordinating many metal ions. The geometry and the stereogenic group inserted in the diamine backbone or aryl aldehyde backbone have been utilized in the past to efficiently transmit chiral information in a variety of different reactions. In this review we will summarize the important and recent achievements obtained in stereocontrolled reactions in which Al(salen) metal complexes are employed. Several other reviews devoted to the general applications and synthesis of chromium and other metal salens have already been published.

Radical formation in polymeric nickel complexes with N2O2 Schiff base ligands: An in situ ESR and UV–vis–NIR spectroelectrochemical study

A series of electrochemically generated polymeric nickel (II) Schiff base complexes was investigated by in situ electron spin resonance (ESR)/ultraviolet–visible–near infrared (UV–vis–NIR) spectroelectrochemistry and the combination of cyclic voltammetry and quartz crystal microbalance (QCM) techniques. The comparative analysis of the in situ ESR and UV–vis–NIR (including low-energy NIR range) spectra of poly-[Ni(Schiff)] films recorded during their oxidation at ambient temperature was performed, which allowed us to monitor the formation of different charge carriers in the polymer at different doping levels and elucidate their structure as well as the extent of their delocalization. The polymer doping level achieved by its oxidation within selected range of potentials was determined by combining the results of cyclic voltammetry and QCM measurements. The influence of the substituents in the diamine backbone and phenolate moieties of the ligand on the spectroscopic properties of the oxidized polymers and number of electrons per monomer unit exchanged in the redox processes was studied in detail. Integration of data from all techniques allowed us to propose the existence of both inter- and intrachain delocalization of radical cations generated in the doped polymers and show that the highest doping levels (up to two positive charges per a monomer unit) are attained in the poly-[Ni(Schiff)] films with highly localized biphenoxyl radical cations.

A Bifunctional Iridium Catalyst Modified for Persistent Hydrogen Generation from Formic Acid: Understanding Deactivation via Cyclometalation of a 1,2-Diphenylethylenediamine Motif

Thermal degradation of a bifunctional Ir complex with a 1,2-diphenylethylenediamine (DPEN) framework was investigated, which is relevant to catalyst deactivation in the acceptorless dehydrogenation of formic acid. The well-defined hydridoiridium complex 1b, derived from N-triflyl-1,2-diphenylethylenediamine (TfDPEN), proved to be solely transformed at the reflux temperature of 1,2-dimethoxyethane (DME) into two iridacycles (2 and 3) via C–H bond cleavage at the ortho carbon atoms of the phenyl substituents on the diamine backbone. These products were successfully isolated and characterized by NMR, elemental analysis, and X-ray crystallography. The iridacycle formation was significantly enhanced in the presence of water, possibly due to facile deprotonative orthometalation via a hydroxidoiridium intermediate. To prevent the deactivation process caused by the cyclometalation of the DPEN moiety, a hydridoiridium complex (5b) without phenyl substituents was synthesized from N-triflylethylenediamine (TfEN). Th...

Base metal Schiff base complexes applied as catalysts for the oxidation of n-octane

The catalytic oxidation of n-octane to value-added oxygenates has been studied with a series of salen-type complexes of iron. The four iron Schiff base complexes N,N′-bis(salicylidene)-L-iron(III) chloride [L=1,2-phenylenediamine (5); ethylenediamine (6); propylenediamine (7) and butylenediamine (8)] were synthesised by variation of the bridging diamine backbone. All the complexes are fully characterised and the crystal structure of 7 is for the first time reported as a centrosymmetric dimer observed to crystallise in the triclinic P1‾ system. The application of 5–8 in this oxidation reaction represents a rare example of the systematic use of iron-salen complexes for the liquid-phase functionalisation of Csp3–H bonds of straight chain alkanes. All catalysts displayed activity with H2O2 and TBHP as oxidants that resulted in a mixture of oxygenated products dominated by the ketones (2-, 3- and 4-octanones). Observed trends and variations in catalytic activities of the complexes is related to differences in chemical/structural features and changes in reaction conditions. A detailed analysis of selectivity parameters of the complexes to the variety of oxygenates is also presented and rationalised.

Chiral N-Heterocyclic Carbene Ligand Enabled Nickel(0)-Catalyzed Enantioselective Three-Component Couplings as Direct Access to Silylated Indanols.

An enantioselective nickel(0)-catalyzed reductive three-component coupling between aromatic aldehydes, norbornenes, and silanes affords directly silyl-protected indanol derivatives. A new bulky chiral C2-symmetric NHC (NHC = N-heterocyclic carbene) ligand basing on the 1,2-di(napthalen-1-yl)ethylene diamine backbone allows accessing the annulated products as single diastereoisomers in high enantioselectivity.

Spectroscopic and molecular modeling methods to study the interaction between naphthalimide-polyamine conjugates and DNA

The effect of polyamine side chains on the interaction between naphthalimide-polyamine conjugates (1–7) and herring sperm DNA was studied by UV/vis absorption and fluorescent spectra under physiological conditions (pH=7.4). The diverse spectral data and further molecular docking simulation in silico indicated that the aromatic moiety of these compounds could intercalate into the DNA base pairs while the polyamine motif might simultaneously locate in the minor groove. The triamine compound 7 can interact more potently with DNA than the corresponding diamine compounds (1–6). The presence of the bulky terminal group in the diamine side chain reduced the binding strength of compound 1 with DNA, compared to other diamine compounds (2–6). In addition, the increasing methylene number in the diamine backbone generally results in the elevated binding constant of compounds–DNA complex. The fluorescent tests at different temperature revealed that the quenching mechanism was a static type. The binding constant and thermodynamic parameter showed that the binding strength and the type of interaction force, associated with the side chains, were mainly hydrogen bonding and hydrophobic force. And the calculated free binding energies of molecular docking are generally consistent with the stability of polyamine–DNA complexes. The circular dichroism assay about the impact of compounds 1–7 on DNA conformation testified the B to A-like conformational change.

Metal Ion Complexes of N,N'-Bis(2-Pyridylmethyl)-trans-1,2-Diaminocyclohexane-N,N'-Diacetic Acid, H2bpcd: Cis/Trans Isomerization Equilibria.

The synthesis of N,N'-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane-N,N'-diacetic acid (H2bpcd) and its complexation of Ga(III) and Co(III) are reported. H2bpcd and the metal-bpcd(2-) complexes, isolated as hexafluorophosphate salts, were characterized by elemental analysis, X-ray crystallography, IR spectroscopy, and (1)H and (13)C NMR spectroscopy. [Ga(bpcd)]PF6, [Ga(C22H26N4O4)]PF6, crystallized in the orthorhombic space group Ibca, with a = 13.8975(7) Å, b = 15.0872(7) Å, c = 22.2418(10) Å, and Z = 8. Ga is coordinated in a distorted octahedral geometry provided by a N4O2 donor atom set with trans-monodentate acetate groups and cis-2-pyridylmethyl N atoms, i.e., the trans-O,O isomer. The diamagnetic [Co(bpcd)]PF6, [Co(C22H26N4O4)]PF6, also crystallized from solution in the Ibca space group as the trans-O,O isomer. The (1)H and (13)C assignments for H2bpcd and metal-bpcd(2-) complexes were made on the basis of 2D COSY and HSQC experiments, which were used to differentiate among three possible isomers, i.e., one cis (C1 symmetry) and two trans (C2 symmetry). NMR results indicate that the [Ga(bpcd)](+), [Co(bpcd)](+), and cis-O,O, cis-Npy,Npy-[Ga(bppd)](+) cations, where bppd(2-) stands for bis(2-pyridylmethyl)-1,3-diaminopropane diacetate, are present in solution as isomers with the same symmetry as observed in the solid state. The crystallographic data and the dramatic shift that occurs in the position of the cis/trans isomerization equilibria for the [Ga(bpad)](+) cations simply by increasing the number of bridging CH2 groups in the ligand's diamine backbone represent a unique opportunity to assess the accuracy of modern computational methods. The performance of several local density functionals using a pseudopotential-based SDD basis set was compared with the more rigorous HF and MP2 ab initio calculations. The SVWN5 and SV5LYP functionals provide significantly better Ga-O and Ga-N distances than the HF method or the nonlocal BLYP functional. However, to provide proper isomerization energies the pseudopotential-DFT calculations must be augmented by MP2 single-point energies and calculations of solvation free energies.

A Mononuclear Manganese Complex of a Tetradentate Nitrogen Ligand – Synthesis, Characterizations, and Application in the Asymmetric Epoxidation of Olefins

AbstractA new chiral manganese complex (C1) bearing a tetradentate nitrogen ligand containing chiral bipyrrolidine and benzimidazole moieties was prepared. The structure of C1 was confirmed by ESI‐MS and crystallography. This manganese complex is an active catalyst for the asymmetric epoxidation of various olefins with excellent conversion (up to 99 %) and high enantiomeric excess (up to 96 % ee) with hydrogen peroxide as the oxidant in the presence of 2‐ethylhexanoic acid or acetic acid. Compared with previous structurally similar manganese complexes with different diamine backbones (C2, cyclohexanediamine; C3, diamine from L‐proline), C1 showed improved asymmetric induction, especially for simple olefins such as styrene derivatives and substituted chromene. The possible reasons for the improvement of the ee values are discussed in the text on the basis of the crystal structures of the manganese complexes.

One-pot diastereoselective assembly of helicates based on a chiral salen scaffold

The one-pot reaction of (1S,2S)-(+)-1,2-diaminocyclohexane, 3-tert-butyl-2-hydroxybenzaldehyde and Zn(OAc)2·1.5H2O in methanol under reflux gives the diastereoselective formation of the first zinc(II)-salen double helicate, P-(S, S)-1, which adopts a right-handed helicity. The stereochemistry of the helicates can be readily tuned through varying the chiral diamine backbone.

Mechanistic basis for high stereoselectivity and broad substrate scope in the (salen)Co(III)-catalyzed hydrolytic kinetic resolution.

In the (salen)Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of terminal epoxides, the rate- and stereoselectivity-determining epoxide ring-opening step occurs by a cooperative bimetallic mechanism with one Co(III) complex acting as a Lewis acid and another serving to deliver the hydroxide nucleophile. In this paper, we analyze the basis for the extraordinarily high stereoselectivity and broad substrate scope observed in the HKR. We demonstrate that the stereochemistry of each of the two (salen)Co(III) complexes in the rate-determining transition structure is important for productive catalysis: a measurable rate of hydrolysis occurs only if the absolute stereochemistry of each of these (salen)Co(III) complexes is the same. Experimental and computational studies provide strong evidence that stereochemical communication in the HKR is mediated by the stepped conformation of the salen ligand, and not the shape of the chiral diamine backbone of the ligand. A detailed computational analysis reveals that the epoxide binds the Lewis acidic Co(III) complex in a well-defined geometry imposed by stereoelectronic rather than steric effects. This insight serves as the basis of a complete stereochemical and transition structure model that sheds light on the reasons for the broad substrate generality of the HKR.

Synthesis, characterization and X-ray structures of enatiopure-diamine zinc(II) complexes as pre-catalysts for stereoselective production of poly(rac-lactide)

Two novel dichlorozinc complexes, (peeda)ZnCl2 and (pepda)ZnCl2, where peeda is N1,N2-bis{(R)-1-phenylethyl}ethane-1,2-diamine and pepda is N1,N3-bis{(R)-1-phenylethyl}propane-1,3-diamine, were synthesised and characterised by X-ray diffraction. Dialkyl derivatives of these compounds, generated in situ, efficiently initiated the ring-opening polymerisation (ROP) of rac-lactide (rac-LA). The backbone links, composed of diamine units, had a significant influence on the degree of stereoselectivity in the resulting heterotactic polylactide (PLA). Increased flexibility of the diamine backbone resulted in enhanced heterotacticity. (pepda)ZnMe2 produced heterotactic PLA with a Pr of 0.78 at −25°C.

Probing differences in binding of methylbenzylamine enantiomers to chiral cobalt(ii) salen complexes

In this work, we investigate the mode of chiral interactions between the asymmetric Co(II) salen complex, (S,S)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-diamine-Co(II) ([Co(1)]), and single enantiomers of methylbenzylamine (MBA) using different continuous-wave and pulsed electron paramagnetic resonance techniques combined with density functional theory computations. While [Co(1)] displays a large affinity for binding a single MBA molecule, it has a much weaker affinity for binding a second MBA molecule. Subtle differences are detected in the EPR spectra of the homochiral (S,S-[Co(1)](S-MBA)) and heterochiral (S,S-[Co(1)](R-MBA)) adducts using low [Co(1)] : MBA ratios. Moreover at high concentrations of racemic MBA, a strong preference (80%) is observed for the formation of the bis-ligated heterochiral adduct (S,S-[Co(1)](R-MBA)(2)) compared to the homochiral analogue (20% of S,S-[Co(1)](S-MBA)(2)). Differences in the (14)N hyperfine coupling from the diamine backbone in [Co(1)] were also evidenced by hyperfine sublevel correlation (HYSCORE), revealing magnetically equivalent N nuclei for the homochiral adducts and inequivalent N nuclei for the heterochiral adducts. Using DFT, these slight differences were reproduced, and explained based upon the different modes of alignment of the MBA molecule in the adduct. The current findings therefore reveal the appreciable enantiodiscrimination that occurs during the binding of MBA enantiomers to the chiral Co(II) salen complex.