Pendant Side Arm Research Articles

Comparison of the equilibrium, kinetic and water exchange properties of some metal ion-DOTA and DOTA-bis(amide) complexes

The 1,7-diacetate-4,10-diacetamide substituted 1,4,7,10-tetraazacyclododecane structural unit is common to several responsive Magnetic Resonance Imaging (MRI) contrast agents (CAs). While some of these complexes (agents capable of sensing fluctuations in Zn2+, Ca2+ etc. ions) have already been tested in vivo, the detailed physico-chemical characterization of such ligands have not been fully studied. To fill this gap, we synthesized a representative member of this ligand family possessing two acetate and two n-butylacetamide pendant side-arms (DO2A2MnBu = 1,4,7,10-tetraazacyclodoecane-1,7-di(acetic acid)-4,10-di(N-butylacetamide)), and studied its complexation properties with some essential metal and a few lanthanide(III) (Ln(III)) ions. Our studies revealed that the ligand basicity, the stability of metal ion complexes, the trend of stability constants along the Ln(III) series, the formation rates of the Ln(III) complexes and the exchange rate of the bound water molecule in the Gd(III) complex fell between those of Ln(DOTA)− and Ln(DOTA-tetra(amide))3+ complexes (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, DOTAM = 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane). The only exception is the stability of Cu(DO2A2MnBu) which was found to be only slightly lower than that of Cu(DOTA)2− (log KCuL = 19.85 vs. 21.98). This is likely reflects exclusive coordination of the negatively charged acetate donor atoms to the Cu2+ ion forming an octahedral complex with the amides remaining uncoordinated. The only anomaly observed during the study was the rates of acid assisted dissociation of the Ln(III) complexes, which occur at a rate similar to those observed for the Ln(DOTA)− complexes. These data indicate that even though the Ln(DO2A2MnBu)+ complexes have lower thermodynamic stabilities, their kinetic inertness should be sufficient for in vivo use.

Diminishing accessibility of electrophilic nickel(ii) centres due to incorporation of a methylene spacer in the pendant side arm of a series of heterotrinuclear nickel(ii)/sodium complexes: a DFT study using a homodesmotic equation

The ethoxy groups have a dual effect in hindering the attack of the pseudo-halides on the nickel(ii) centre and also in stabilizing the complex by intra-molecular interactions.

Correction: Diminishing accessibility of electrophilic nickel(ii) centres due to incorporation of a methylene spacer in the pendant side arm of a series of heterotrinuclear nickel(ii)/sodium complexes: a DFT study using a homodesmotic equation

Correction for ‘Diminishing accessibility of electrophilic nickel(ii) centres due to incorporation of a methylene spacer in the pendant side arm of a series of heterotrinuclear nickel(ii)/sodium complexes: a DFT study using a homodesmotic equation’ by Prasanta Kumar Bhaumik et al., CrystEngComm, 2020, 22, 2970–2977, DOI: 10.1039/D0CE00251H.

Synthesis, structure and metal ion coordination of novel benzodiazamacrocyclic ligands bearing pyridyl and picolinate pendant side-arms

Complex formation of benzodiazacrown ethers with heavy and transition metal ions was studied using NMR spectroscopy, potentiometry and X-ray crystallography.

Observation of an anion⋯anion interaction in a square planar copper(II) Schiff base complex: DFT study and CSD analysis

A centrosymmetric square planar bis-ligand copper(II) complex, [Cu(HL)2](ClO4)2, with a potential tetradentate Schiff base, HL = 2-(2-(ethylamino)ethyliminomethyl)-6-ethoxyphenol, containing pendant side arm, has been prepared and characterized by elemental and spectral analysis and single crystal X-ray diffraction studies. The potential tetradentate Schiff base is trapped in its zwitterionic form and shows a bidentate bonding mode. Several weak forces like hydrogen bonding and CH∙∙∙π interactions lead to the formation of supra-molecular architecture. The existence of an anion⋯anion interaction between the perchlorate anions have been analyzed using DFT calculations, the Bader’s theory of atoms-in-molecules (AIM) and the non-covalent interaction index (NCI plot). The O⋯O distance is 2.848(2) Å.

Enantiomeric Recognition of d- and l-Lactate by CEST with the Aid of a Paramagnetic Shift Reagent.

A previous report demonstrated that EuDO3A could be used as an NMR shift reagent for imaging extracellular lactate produced by cancer cells using CEST imaging. In this work, a series of heptadentate macrocyclic YbDO3A-trisamide complexes with δ-chiral carbons in the three pendant side-arms were examined as shift reagents for lactate detection. High resolution 1H NMR spectra and DFT calculations provided evidence for the formation of stereoselective lactate·YbDO3A-trisamide complexes each with a different CEST signature. This stereoselectivity allowed discrimination of d- versus l-lactate by both high-resolution NMR and CEST. This work demonstrates that lanthanide-based paramagnetic shift reagents can be designed to detect important metabolites by CEST MRI selectively.

A mechanistic study on unexpected and solvent-based pH-tuneable role of benzylic pendant side-arm on N2O2-donor naphthodiaza-crown macrocyclic ligand as a sensitive fluorogenic chemosensor for Al3+ in aqueous solution: X-ray, NMR, photophysical, and computational studies

Herein, we describe for the first time synthesis, characterization, chemosenor behavior, and mechanism of metal ion-ligand interaction of two novel side-armed naphthodiaza-crown macrocycles (L1 and L2) by employing of IR, 1H and 13C NMR, UV–vis, fluorescence spectroscopy, CHN microanalysis and single crystal X-ray diffraction. Preliminary fluorescence studies in ethanol as solvent revealed that the metal ion recognition by L1 was strongly different from L2 suggesting the importance of the number of benzylic side-arms on the extent of the interaction with Mn+. For instance employing fluorescence titration in ethanol showed binding constant values 105M−1 and 2.6×106M−1 for L1/Al3+ and L2/Al3+, respectively. Such metal ion selectivity by L2, however, was sharply improved in aqueous media (1:1v/v ethanol/water) in comparison with L1. The selective complex formation of L2 with Al3+ supported very low limit of detections, i.e. 5×10−7 and 7×10−6M in ethanol and aqueous medium, respectively. Single crystal X-ray diffraction analysis (in solid) as well as 1H NMR spectroscopy in acidic DMSO-d6 solvent revealed that unparalleled direction of the electron lone pairs on the donor atoms of L2 could not let Al3+ cation to be coordinated simultaneously by both nitrogen-donor groups on the macrocycle ring. The coordination of Al3+ with both of those nitrogen donors on L2, however, was evident from the 1H NMR spectra of L2/Al3+ where the solvent was DMSO-d6.

A combined experimental and theoretical study on supramolecular assemblies in octahedral cobalt(III) salicylaldimine complexes having pendant side arms

Two mononuclear cobalt(III) complexes, [Co(L1)(N3)2(deen)] (1) and [Co(L2)(N3)2(DMSO)] (2), where HL1 {2-(2-(diethylamino)ethyliminomethyl)-4-bromophenol} and HL2 {2-(2-(diethylamino)ethyliminomethyl)-6-methoxyphenol} are tridentate and tetradentate Schiff bases, respectively and deen is a bidentate chelating ligand, N,N-diethyl-1,2-diaminoethane, were prepared and characterized by elemental and spectral analysis. X-ray crystal structure determination confirmed their structures. Both complexes are meridional isomers. The solid state structures show the participation of the organic ligands in concurrent conventional and unconventional CH⋯π interactions along with hydrogen bonding. The energetic features of these interactions have also been studied by means of DFT calculations.

Synthesis and metal ion extraction of partial-cone di-ionizable p-tert-butylcalix[4]arene-1,2-crown-5 ligands with elongated acidic side arms

Proton di-ionizable calix[4]arene-1,2-crown-5 ligands with elongated pendant side arms are synthesized in the partial-cone conformation. Solvent extraction studies probed the influence of elongated side arms and conformation toward various metal cations. Results of the solvent extraction experiments show that these compounds are poor extractants from aqueous solutions into chloroform for hard alkali metal cations and alkaline earth metal cations and intermediate Pb2+. For soft Hg2+, the ligands with N-(X)sulfonyl carbamoyl ionizable groups exhibit very good to excellent extraction efficiency. In general, the metal ion extraction behavior for the new partial-cone conformers is quite similar to that reported recently for their cone conformational isomers.

Stereoselective Polymerization of rac-Lactide Catalyzed by Zinc Complexes with Tetradentate Aminophenolate Ligands in Different Coordination Patterns: Kinetics and Mechanism.

A series of monomeric zinc silylamido complexes bearing [NNNO]-type tetradentate aminophenolate ligands, LZnN(SiMe3)2 [L = {(2-R(1))ArCH2N[(CH2)2R(2)]CH2(4-R(4)-6-R(3))C6H2O-}, R(1) = NMe2, R(2) = N(i)Pr2, R(3) = R(4) = Cl (1), R(3) = R(4) = cumyl (3); R(1) = NMe2, R(2) = NEt2, R(3) = R(4) = cumyl (2), R(3) = CPh3, R(4) = Me (4); R(1) = NEt2, R(2) = NEt2, R(3) = CPh3, R(4) = Me (5); R(1) = NMe2, R(2) = (S)-1-butylpyrrolidin-2-yl, R(3) = R(4) = cumyl (6), R(3) = CPh3, R(4) = Me (7)], have been synthesized via reactions of Zn[N(SiMe3)2]2 and 1 equiv of the corresponding aminophenols. The monomeric nature and versatile coordination patterns of these complexes in the solid state were further confirmed by X-ray diffraction studies on complexes 2, 3, 5, and 7. In complex 3, the N,N-diisopropylamino group on the pendant side arm does not coordinate to the metal center; only the remaining three donors of the aminophenolate ligand and the silylamido group interact with the zinc center. By contrast, in complexes 2, 5, and 7, the amino group of the aryl moiety does not coordinate to the metal center, while the amino group on the pendant side arm coordinates. At room temperature, the above-mentioned structural features of these complexes are retained in solution, as confirmed by (1)H NMR spectroscopy. Complexes 1-7 proved to be efficient initiators for the ring-opening polymerization of rac-lactide (rac-LA) at ambient temperature, and the polymerizations were better controlled in the presence of 2-propanol. The coordination pattern of the aminophenolate ligand exerted a significant influence on the stereoselectivity of the corresponding complex toward the polymerization of rac-LA, leading to the production of heterotactic biased polylactides (PLAs) by complexes 1 and 3 (Pm = 0.40-0.46) and moderately to highly isotactic PLAs by complexes 2 and 4-7 (Pm = 0.70-0.81). Detailed kinetic investigations revealed a first-order dependence on the monomer concentration for all complexes and different orders in the initiator concentration ranging from 1.78 to 1.81. The nature of the solvent as well as the molar ratio of the zinc complex and 2-propanol also displayed certain influence on the order of rac-LA polymerization in the initiator concentration. Factional orders of 1.80, 1.38, and 1.11 were obtained by using complex 5/(i)PrOH (1:1) in toluene and tetrahydrofuran and complex 5/(i)PrOH (1:2) in toluene, respectively. On the basis of DOSY and (1)H and (13)C NMR studies of zinc alkoxide model complexes "LZn(OCMe2COOMe)" as well as the fractional orders of 1.78-1.81 in the initiator concentration, activation/insertion processes likely involving more than one monomeric active species were then hypothesized.

Positional isomerism of unsymmetrical semirigid ligands toward the construction of discrete and infinite coordination architectures of zinc(ii) and cadmium(ii) complexes

Three unsymmetrical semirigid ligands, HInMe-n-py (n = 2, 3, 4), showing positional isomerism have assembled with ZnCl2 and CdCl2 to yield supramolecular coordination assemblies. Compound [Zn(InMe-2-py)2]·1/2THF·1/2CH3OH·1/4H2O (1) has a two-dimensional rhombus gridlike (4,4) layer structure constructed from the dinuclear paddlewheel [Zn2(O2C)4N2] units with two pendant side-arms. Compound [Zn2Cl2(InMe-3-py)2(HInMe-3-py)2] (2) forms a discrete armed M2L2 macrocycle, which connects with others by intermolecular O–H⋯O and C–H⋯Cl hydrogen bonds to give rise to a decorated three-dimensional supramolecular pcu net. Compound [Zn(InMe-4-py)2]·1/2H2O (3) adopts a two-dimensional chiral wavy (4,4) square grid. Opposite-handedness chiral wavy grids are stacked in an ABAB type of sequence that has small voids accommodating lattice water molecules. Compound [CdCl(InMe-3-py)] (4) displays a two-dimensional achiral meso layer in which the opposite-handedness Cd–L helical chains are interconnected by the Cd–O bridging bonds and stitched by zigzag Cd–Cl chains. Compound [Cd(InMe-4-py)2(H2O)2] (5) features a two-dimensional rhombus gridlike (4,4)-net. Through the connections of net-to-net O–H⋯O hydrogen bonds, the grids are offset-stacked to be a hydrogen-bonded three-dimensional oblique pcu net. The structural diversity and complexity in these supramolecular coordination architectures are most likely attributed to the various coordination modes adopted by these N- and O-donor ligands of different substituent position and the coordination preference exhibited by the metal ions. Thermogravimetric (TG) analyses showed that all the frameworks of compounds 1–5 exhibit a thermal stability higher than 300 °C. In addition, the solid-state photoluminescent properties of compounds 1–5 were investigated.

“One Ring to Bind Them All”—Part II: Identification of Promising G‐Quadruplex Ligands by Screening of Cyclophane‐Type Macrocycles

A collection of 26 polyammonium cyclophane-type macrocycles with a large structural diversity has been screened for G-quadruplex recognition. A two-step selection procedure based on the FRET-melting assay was carried out enabling identification of macrocycles of high affinity (ΔT1/2 up to 30°C) and high selectivity for the human telomeric G-quadruplex. The four selected hits possess sophisticated architectures, more particularly the presence of a pendant side-arm as well as the existence of a particular topological arrangement appear to be strong determinants of quadruplex binding. These compounds are thus likely to create multiple contacts with the target that may be at the origin of their high selectivity, thereby suggesting that this class of macrocycles offers unique advantages for targeting G-quadruplex-DNA.

Functional Sidearm Promoted Electron-Transfer Reactions: A New Route to Metallacarboranes Incorporating the η7-arachno-Carboranyl Ligands

Reactions of [nido-(Me2NCH2CH2)RC2B10H10]Na2 (R = H, MeOCH2CH2, Me2NCH2CH2) with ZrCl4(THF)2 or SmI2(THF)x gave unprecedentedly metallacarboranes with η7-arachno-carboranyl ligands, in which the heteroatom-containing pendant sidearms are both electronically and entropically necessary for the formation of such complexes with the central metal ions in the highest oxidation state.

(1,4,8,11-Tetraazacyclotetradeca-1,4,8,11-tetrayl)tetraacetamide-kappa6N1,N4,N8,N11,O1,O8]copper(II) sulfate 4.5-hydrate.

The crystal structure of the title copper(II) complex, [Cu(C(18)H(36)N(8)O(4))]SO(4).4.5H(2)O, formed with the tetraamide cyclam derivative 2-(4,8,11-triscarbamoylmethyl-1,4,8,11-tetraazacyclotetradec-1-yl)acetamide (TETAM), is described. The macrocycle lies on an inversion centre occupied by the hexacoordinated Cu atom. The four macrocyclic tertiary amines form the equatorial plane of an axially Jahn-Teller elongated octahedron. Two O atoms belonging to two diagonally opposite amide groups occupy the apical positions, giving rise to a trans-III stereochemistry, while both the remaining pendant side arms extend outwards from the macrocyclic cavity and are engaged in hydrogen bonds with sulfate anions and co-crystallized water molecules.

Efficient syntheses of polymerisable pendant arm azamacrocycles and formation of poly(vinylbenzyltriazacyclododecane)

Synthetic routes to a number of metal-free triazacyclo-dodecane derivatives featuring the unsymmetrical incorporation of polymerisable pendant side arms such as vinylbenzene and methacrylate have been developed; the structure of a nitrate salt of the vinylbenzene-substituted species has been determined by single crystal X-ray diffraction and the first polymer-bound triazamacrocycles formed via free-radical polymerisation of a metal-free macrocycle-containing monomer.

Synthesis and characterisation of chelating polycarboxylate ligands capable of forming intermolecular, complementary triple hydrogen bonds

The reaction between the dianhydride of ethylenedinitrilotetraacetic acid (edta) 1 and aminouracil derivatives was utilised to synthesize bifunctional, chelating ligands capable of co-ordinating to a metal centre via the edta backbone, while simultaneously being able to form complementary intermolecular hydrogen bonds via the uracil moieties. 5-Aminouracil 2, 5-aminoorotic acid 3, 5,6-diaminouracil 4 and 5,6-diamino-2-thiouracil 5 were treated with 1 in dry dmf or dmso to give functionalised dicarboxamide derivatives H2L1–H2L4 in 15–90% yield. The 5,6-diaminouracils 4 and 5 reacted with the dianhydride exclusively via the 5-amino position. The reaction of H2L1–H2L4 with basic metal salts [e.g. KVO3 and Zn(O2CMe)2] in aqueous solutions led to the formation of metal complexes of the anionic ligands L1–L4: K[VO2L1]·5H2O, [Zn(OH2)L1]·4H2O and [Zn(OH2)L3]·5H2O were characterized by single-crystal X-ray crystallography. The solid state structures of these complexes show that the uracil moieties are situated on pendant side-arms. The high degree of rotational freedom of these hydrogen-bonding groups makes this class of metal complex promising in terms of specific binding to water-soluble biomolecules having complementary hydrogen-bonding sites.

Pd.H-C Interactions. Preparation and Structure of Orthometalated Tetranuclear Complexes of Palladium(II) and Platinum(II).

The reaction of 2-(1-naphthyl)benzothiazoline with palladium(II) acetate leads to helical mononuclear and orthometalated tetranuclear products. The molecular structures of mononuclear palladium(II) [Pd(H1-nabz)(2)] (1) (H(2)1-nabz = 2-N-(1-naphthylmethylideneamino)benzenethiolate), tetranuclear palladium(II) [Pd(4)(1-nabz)(4)] (2) and tetranuclear platinum(II) [Pt(4)(1-nabz)(4)] (3) have been determined by single-crystal X-ray diffraction method. Crystal data for complex 1 are as follows: a = 14.208(3) Å, b = 18.227(4) Å, c = 14.398(8) Å; beta = 94.55(3) degrees; V = 3717.0(23) Å(3); space group = P2(1)/n, Z = 4. Crystal data for the complex 2 are as follows: a = b = 15.798(3) Å, c = 23.728(4) Å; V = 5921.7(20) Å(3); space group = I4(1)/a, Z = 16 for the Pd(1-nabz) unit. Crystal data for the complex 3 are as follows: a = b = 15.496(2) Å, c = 24.348(3) Å; V = 5846.3(20) Å(3); space group = I4(1)/a, Z = 16 for the Pt(1-nabz) unit. The mononuclear palladium(II) complex reveals short ortho-hydrogen.palladium distances of 2.66(7) and 2.48(7) Å. These short distances and (1)H NMR studies provide a M.H-C interaction which can be regarded as a three-center four-electron interaction. The molecular structures of 2 and 3 confirm the formation of unusual tetranuclear compounds featuring a rare C,N,S-tridentate ligand derived from orthometalation of pendant side arm. The structural and chemical properties of the mononuclear palladium(II) complex 1 clearly suggest that 1 is a potential intermediate in the formation of the tetranuclear complex 2 by orthometalation reactions.