Pendant Carboxymethyl Groups Research Articles

Thermosensitive Poloxamer-graft-Carboxymethyl Pullulan: A Potential Injectable Hydrogel for Drug Delivery.

A thermosensitive copolymer composed of amphiphilic triblock copolymer, poloxamer 407, grafted on hydrophilic pullulan with pendant carboxymethyl groups (CMP) was prepared and characterized. The structure of the new copolymer was assessed by Fourier transform infrared (FT-IR) and 1H nuclear magnetic resonance (1H NMR) spectroscopy. The content of the poloxamer in the grafted copolymer was 83.8% (w/w). The effect of the copolymer concentration on the gelation behavior was analyzed by the vertical method and rheological tests; the gel phase of the copolymer occurred at a lower concentration (11%, w/v) as compared with poloxamer (18%, w/v). The starting gelation time under the simulated physiological conditions (phosphate buffer with a pH of 7.4, at 37 °C) was sensitive on the rest temperature before the test, this being 990 s and 280 s after 24 h rest at 4 °C and 20 °C, respectively. The rheological tests evidenced a high elasticity and excellent ability of the copolymer to recover the initial structure after the removal of the applied force or external stimuli. Moreover, the hydrogel has proved a sustained release of amoxicillin (taken as a model drug) over 168 h. Taken together, the results clearly indicate that this copolymer can be used as an injectable hydrogel.

Synthesis and Protonation Constants of an Amide-Based Chelating Cyclophane

Our research group have reported that, under high dilution conditions, condensation reactions between 4,4’-ethylenebis(2,6-morpholinedione), 1, and aromatic diamines gave a new series of tetraaza chelating cylophanes, which have amide and aromatic groups in the ring framework and pendant carboxymethyl groups [1].[...]

Solution 1H n.m.r. of paramagnetic Co2+complexes with dioxobis(carboxymethyl)tetraazamacrocycles

Paramagnetic shifts in the 1H n.m.r. spectra were observed for high-spin Co2+ complexes with 12--14-membered tetraazamacrocycles incorporating two amide groups and two pendant carboxymethyl groups. The pseudocontact term due to the dipolar interaction between the metal ion and the resonant protons was calculated on the basis of X-ray structures, and the Fermi contact term due to spin delocalization was determined. The ethylenediamine moiety of the ligand molecule is coordinated in an unsymmetric manner, even in solution, and internal motion (involving conformational change of the macrocyclic frame and exchange of coordinate bonds) is much slower than the n.m.r. observation frequency. In the 12-membered macrocyclic complex Co(L12), three of the eight CH2 groups fix their orientation in the n.m.r. time scale; in Co(L13) only one CH2 group fixes its orientation; in Co(L14) all CH2 groups undergo a rapid reorientation. The facility in internal motion increases with the ring size, and shows a correlation with the chemical stabilities of these Co2+ complexes against oxidation; to atmospheric oxygen, Co2+(L12) is the most resistant and Co2+(L14) is the most susceptible.

Zinc(II) complexes of xylyl bridged bis(1,4,7-triazacyclononane) derivatives

The xylyl bridged bis(tacn) ligands, T 2- o-X (1,2-bis(1,4,7-triazacyclonon-1-ylmethyl)benzene) and T 2- p-X (1,4-bis(1,4,7-triazacyclonon-1-ylmethyl)benzene) have yielded one mononuclear, [Zn(T 2- o-X)](ClO 4) 2 ( 1), and one dinuclear complex [Zn 2(T 2- p-X)(H 2O) 4(DMF) 2][ZnCl 4] 2 ( 2). A single-crystal X-ray structure determination of 1 has established that T 2- o-X ligand sandwiches a single zinc(II) centre, which adopts a distorted octahedral geometry. A structural analysis of 2 confirmed the formation of a binuclear [Zn 2(T 2- p-X)(H 2O) 4(DMF) 2] 4+ complex in which each zinc centre binds to one of the macrocyclic compartments of the T 2- p-X ligand and the remaining zinc coordination sites are occupied by water and DMF ligands. The coordination of DMF highlights the ability of carbonyl groups in amide molecules to bind to zinc(II), a feature of zinc enzymes that catalyse the hydrolysis of amide bonds in proteins (peptidases). A synthetic procedure has been developed which enables single pendant carboxymethyl groups to be attached to T 2- o-X and T 2- m-X. These bis(tetradentate) ligands form dinuclear zinc(II) complexes [Zn 2(T 2- o-X Ac 2)(H 2O) 4](ClO 4) 2·2H 2O ( 3) and [Zn 2(T 2- m-X Ac 2)(H 2O) 4](ClO 4) 2·2H 2O ( 4), whose structure has been probed by spectroscopic methods.

Synthesis and characterization of cobalt(II) complex with a di- N-carboxymethylated tetraaza macrocycle

The complex [ Co( H 2 L)] Cl 2·4 H 2 O ( 1 ) (H 2L=2,13-bis(2-carboxymethyl)-5,6-dimethyl-2,6,13,17-tetraazatricyclo[14,4,0 1.18,0 7.12]docosane) has been synthesized and structurally characterized. The title compound contains a centrosymmetric cation with the chloride anions and water molecules. The coordination geometry around the cobalt(II) ion is a distorted octahedron with the secondary and tertiary amines of the macrocycle and two oxygen atoms of the pendant carboxymethyl groups. Electronic spectra and effective magnetic moment of the complex also reveal a high-spin six-coordinated geometry.

Synthesis and characterization of copper(II) and nickel(II) complexes of a di- N-carboxymethylated tetraaza macrocycle

The reaction of 3,14-dimethyl-2,6,13,17-tetraazatricyclo[14,4,0 1.18,0 7.12]docosane (L 1) with bromoacetic acid produced the macrocycle (L 2=2,13-bis(2-carboxymethyl)-3,14-dimethyl-2,6,13,17-tetraazatricyclo[14,4,0 1.18,0 7.12]docosane) in which two carboxymethyl groups are appended. The complexes [NiL 2]·4H 2O ( 2) and [CuL 2]·4H 2O ( 3) have been prepared and characterized. The two pendant carboxymethyl groups of the macrocyclic ligand are trans to each other, and the absolute configuration is a trans-III in the solid state. The crystal structures of 2 and 3 revealed an axially elongated octahedral geometry with four nitrogen atoms of the macrocycle and two oxygen atoms of the pendant arms at the axial positions. The nickel(II) and copper(II) ions are located at an inversion center. Macrocycle L 2 reacts more rapidly with metal (II) ions than does L 1. Spectra and electrochemical behaviors of the complexes are also discussed.

Binuclear Gd3+ Complex of a 34-Membered Macrocycle with Six Carboxymethyl Arms: X-ray Structures, Formation Constants, NMR, EPR, and 1H NMR Relaxivities

A 34-membered macrocyclic ligand with six pendant carboxymethyl groups has been synthesized by the coupling of two diethylenetriaminepentaacetate (dtpa) and two 1,4-diaminobutane units: the macroc...

A novel two-dimensional zinc(II) complex of a di-N-carboxymethylated tetraaza macrocycle linked by hydrogen-bonds

The complex [ZnL]·10H2O (L = 2,13-bis(2-carboxymethyl)-3,14-dimethyl-2,6,13,17-tetraazatricyclo[14,4,01.18,07.12]docosane) has been synthesized and structurally characterized. It crystallizes in the monoclinic system, space group P21/c with a = 10.159(1), b = 10.066(3), c = 17.268(2) A, β = 102.92(1)°, V = 1721.0(5) A3, and Z = 2. The crystal structure reveals an axially elongated octahedral geometry with bonds from the zinc(II) ion to the secondary and tertiary amines of the macrocycle and two oxygen atoms of the pendant carboxymethyl groups. The molecules of the zinc(II) complex are connected into a two-dimensional chain via hydrogen bonds.

Molecular recognition of phenethylamine, tyramine and dopamine with new anionic cyclophanes in aqueous media

Water-soluble cyclophanes functionalized by amide groups and pendant carboxymethyl groups have been synthesized, in a single step, by a condensation reaction between ethylenediaminetetraacetic (EDTA) dianhydride and bis(4-aminophenyl) ether or bis(4-aminophenyl)methane: cyclophanes obtained are 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33-octaaza-17,40-dioxa[10.1.10.1]paracyclophane (1) and 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33-octaaza[10.1.10.1]paracyclophane (2). Their complexation with 2-phenylethylamine (phenethylamine), 2-(4-hydroxyphenyl)ethylamine (tyramine) and 2-(3,4-dihydroxyphenyl)ethylamine (dopamine), which have biologically important activities, has been studied by 1H NMR spectroscopy in aqueous media. The formation constants of 1∶1 host–guest complexes, K = [HG]/[H][G], have been determined as: log K = 0.8 for 1–phenethylamine; 1.2 for 1–tyramine; 1.2 for 1–dopamine; 1.6 for 2–phenethylamine; 2.0 for 2–tyramine. Dopamine and 2 form a complex with low water-solubility. The chemical shifts of aromatic protons of the host and guest molecules suggest the formation of inclusion complexes in solutions. The formation of the host–guest complexes is assisted by a hydrogen bond and/or an electrostatic interaction between the pendant –CH2CO2– group of the host and the –CH2CH2NH3+ arm of the guest molecule. The two types of molecular recognition sites of the new cyclophanes result in the selective complex formation with the aromatic amines.

1H NMR and protonation constants of new metal-chelating macrocycles, oxocyclopolyamines with pendant carboxymethyl groups, and the stabilities of their Mg 2+ and Ca 2+ complexes

Potentiometry and 1H NMR have been used to study the protonation of a new series of 12−, 13−, 15−, 16− and 17-membered metal-chelating macrocycles with two or three pendant carboxymethyl groups. In the 12− and 13-membered macrocycles, ethylenediaminetetraacetate and ethylenediamine or propanediamine units are linked by two amide groups; in the 15−, 16−, and 17-membered macrocycles, diethylenetriaminepentaacetate and diamine units are linked by two amide groups. The protonation constants K n ( n = 1, 2, 3) of these new macrocyclic ligands are significantly smaller than the corresponding values for tetraaza and triaza macrocycles such as 1,4,7,10-tetraazacyclododecane- N, N′, N″, N″′-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane- N, N′, N″-triacetic acid (NOTA). The protonation sites have been identified by measuring the 1H NMR chemical shifts at different pD values. Protonation corresponding to K 1 occurs on the amine nitrogen atoms. In the successive protonations, protons are distributed on the amine nitrogen atoms and the carboxylate oxygen atoms so as to minimize electrostatic repulsion. The low basicities of the amine nitrogen atoms in these new macrocycles are attributable to the introduction of amide groups into the ring system. As a consequence of the low basicities of the macrocycles, the formation constants of their Mg 2+ and Ca 2+ chelates are much lower than the corresponding values of EDTA. The ratio of the two formation constants, K f ( Ca) K f ( Mg) , varies in an unpredictable manner with the size of the macrolytic ligand.

Yttrium(III) and lanthanum(III) complexes of a 15-membered macrocycle with three pendant carboxymethyl groups

The yttrium(III) and lanthanum(III) complexes of 9,14-dioxo-1,4,7,10,13-pentaaza-1,4,7-cyclopentadecanetriacetic acid, namely, diaquabis(9,14-dioxo-O 14 :O 9 -1,4,7,10,13-pentaaza-N 1 ,N 4 :N 7 -1,4,7-cyclopentadecanetriacetato-O 1 ,O 4 :O 7 )diyttrium(III) tetradecahydrate [Y 2 (C 16 H 24 N 5 O 8 ) 2 (H 2 O) 2 ].14H 2 O, and diaquabis(9,14-dioxo-O 14 :O 9 -1,4,7,10,13-pentaaza-N 1 ,N 4 :N 7 -1,4,7-cyclopentadecanetriacetato-O 1 ,O 4 :O 7 )dilanthanum(III) tetradecahydrate, [La 2 (C 16 H 24 N 5 O 8 ) 2 (H 2 O) 2 ].14H 2 O, have a binuclear structure in which two metal ions are located between two macrocycles

A new nonionic macrocyclic gadolinium(III) chelate as a potential magnetic-resonance-imaging contrast agent.

A new GdIII complex of a 17-membered macrocycle with three pendant carboxymethyl groups has been synthesized; the ligand has been obtained in a single step from diethylenetriaminepentaacetic dianhydride (pentetic dianhydride) and 1,4-butanediamine (putrescine). An X-ray crystal analysis has shown that the complex is a nonionic metal chelate with a coordinated water molecule. The near-zero electrical conductivity, 1 omega-1 cm2 mol-1, of a 1 mM solution indicated that the metal chelate is essentially undissociated. The NMR T1 relaxivity is 2.5 s-1 mM-1 at a resonance field of 64 MHz, and 3.4 s-1 mM-1 at 250 MHz. This new GdIII complex is a potentially important magnetic resonance imaging contrast agent.

Structure of a lead(II) complex of a new 13-membered macrocycle with two pendant carboxymethyl groups

(Aqua)[2,9-dioxo-κ 2 O,O'-1,4,7,10-tetraazaκ 2 N 4 ,N 7 -4,7-cyclotridecanediacetato(2 -)-κ 2 O, O'']-lead(II) dihydrate, [Pb(C 13 H 20 N 4 O 6 )(H 2 O)].2H 2 O, M r =589.56, monoclinic, P2 1 /c, a=8.999;1), b=23.055 (1), c=9.382 (1) A, β=108.58 (1) o , V=1845.I (4) A 3 , Z=4, D x =2.12 g cm -3 , λ(Mo Kα)=0.71073 A, μ=92.6 cm -1 , F(000)=1144, T=294 A, R=0.026 for 2829 independent reflections with I>3σ(I). A Pb II ion is coordinated to six atoms from a macrocyclic ligand and an O atom from water. An additional weak coordination bond with an O atom from an adjacent metal chelate molecule results in a binuclear structure

Simultaneous cyclic voltammetry and electrochemical quartz-crystal microbalance study at polymer film-modified electrodes of molecular inclusion of ferrocene by β-cyclodextrin polymer and carboxymethylated β-cyclodextrin polymer as well as ferrocenecarboxylic acid by β-cyclodextrin polymer

The molecular inclusion equilibria accompanying the ferrocene electrode charge transfer, FC/FC +, in host films of condensation polymers of β-cyclodextrin (β-CDP) and of carboxymethylated cyclodextrin (β-CDPA) were investigated. The inclusion equilibria which accompanied the ferrocenecarboxylic acid electrode processes, FCAH(O)/FCA(I) and FCA(O) −/FCA(I), in the β-CDP film host were also studied. Simultaneous cyclic voltammetry (CV) and electrochemical quartz-crystal microbalance (EQCM) experiments were performed for the relevant inclusion and redox systems by means of the polymer film-modified Au/quartz electrodes. The effects of the electrostatic charge of the guest species, controlled by means of the electrode potential and/or by adjusting the pH of the solution, i.e. the pH and/or redox switching, as well as the effect of counter-ions were investigated for the selective guest ingress and egress. It was found that the FC + electro-oxidation product of FC is partially released from the β-CDP film and is fairly well retained in the β-CDPA one, provided that the fixed cation-exchange carboxylic sites are accessible for ion exchange. Acid-base titration of the CDPA film with the use of EQCM as sensor yielded the acid dissociation constant of the pendant carboxymethyl groups, p K a (β-CDPA) = 4.15. The FCA(I) oxidation product of FCAH is partially released from the β-CDP film at pH > p K a(β-CDP/FCAH), and it precipitates inside the film at pH > p K a(β-CDP/FCAH). The acid dissociation constant of FCAH in the β-CDP film, determined by the EQCM sensor, was found to be p K a(β-CDP/FCAH) = 3.9.