A Cyclen‐Based Tetraphosphinate Chelator for the Preparation of Radiolabeled Tetrameric Bioconjugates

The cyclen‐based tetraphosphinate chelator 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrakis[methylene(2‐carboxyethyl)phosphinic acid] (DOTPI) comprises four additional carboxylic acid moieties for bioconjugation. The thermodynamic stability constants (logK_ML) of metal complexes, as determined by potentiometry, were 23.11 for Cu^II, 20.0 for Lu^III, 19.6 for Y^III, and 21.0 for Gd^III. DOTPI was functionalized with four cyclo(Arg‐Gly‐Asp‐D ‐Phe‐Lys) (RGD) peptides through polyethylene glycol (PEG₄) linkers. The resulting tetrameric conjugate DOTPI(RGD)₄ was radiolabeled with ¹⁷⁷Lu and ⁶⁴Cu and showed improved labeling efficiency compared with 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA). The labeled compounds were fully stable in transchelation challenges against trisodium diethylenetriaminepentaacetate (DTPA) and disodium ethylenediaminetetraacetic acid (ETDA), in phosphate buffered saline (PBS), and human plasma. Integrin α_vβ₃ affinities of the non‐radioactive Lu^III and Cu^II complexes of DOTPI(RGD)₄ were 18 times higher (both IC₅₀ about 70 picomolar) than that of the c(RGDfK) peptide (IC₅₀=1.3 nanomolar). Facile access to tetrameric conjugates and the possibility of radiolabeling with therapeutic and diagnostic radionuclides render DOTPI suitable for application in peptide receptor radionuclide imaging (PRRI) and therapy (PRRT).     

Rapid and high-yield solution-phase synthesis of DOTA-Tyr-octreotide and DOTA-Tyr-octreotate using unprotected DOTA

An improved method for the solution-phase derivatization of Tyr³-Lys⁵(Dde)-octreotide (TOC(Dde)) and Tyr³-Lys⁵(Dde)-octreotate (TATE(Dde)) with the macrocyclic chelator DOTA (1,4,7,10-tetraazacyclododecane-N′,N″,N?,N?-tetraacetic acid) has been developed. The fully protected parent peptides were assembled via solid-phase peptide synthesis (SPPS) using Fmoc-strategy. After cleavage from the solid support, disulfide bond formation was carried out using H₂O₂. Both TOC(Dde) and TATE(Dde) were successfully coupled with DOTA in the presence of NHS, EDCI and DIPEA in a water/DMF solvent system. Yields of the coupling reaction were >98% within only 2 h with no detectable formation of sideproducts. This method for the preparation of DOTATOC, DOTATATE and other DOTA-peptide conjugates is therefore a rapid and economic alternative to the currently used methods.     

DOTP versus DOTA as Ligands for Lanthanide Cations: Novel Structurally Characterized CeIV and CeIII Cyclen-Based Complexes and Clusters in Aqueous Solutions

The coordination and redox chemistry of aqueous Ce^IV/III macrocyclic compounds were studied by using the ligands DOTA and DOTP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid), respectively). The hydrolysis tendency of the tetravalent cation in the presence of DOTA is shown to result in the formation of a highly ordered, fluorite-like [Ce^IV₆(O)₄(OH)₄(H₂O)₈(DOTAH)₄] oxo-hydroxo structure both in solution and in the solid state. The lifetime of the analogous species formed in the presence of DOTP was found to be much shorter. Spectroscopic measurements of the latter suggest its similarity to the former. Its gradual decomposition in solution leads to the accumulation of the in-cage complexes [Ce^IVDOTP] and [Ce^IIIDOTP(H₂O)], which were crystallographically characterized in this study. The redox energetics and spectroscopic characteristics for the transition between these two in-cage complexes in aqueous solutions were studied as well. Together with the crystallographic structures of the above-mentioned species, the in-cage [Ce^IVDOTA(H₂O)] complex structure is presented herein for the first time. An elaborative analysis of the X-ray crystallographic structural data obtained for the in-cage complexes studied herein and similar structures published previously suggests that hard-bonding cyclen-derived ligands are, counter-intuitively, better suited for encapsulating, and perhaps kinetically stabilize softer cations than harder ones with DOTP, marked as a possible adequate chelator for the study of the aqueous properties of Ln^II and Ac^III cations.     

Using Native Chemical Ligation for Site-Specific Synthesis of Hetero-bis-lanthanide Peptide Conjugates: Application to Ratiometric Visible or Near-Infrared Detection of Zn2+

The interest in ratiometric luminescent probes that detect and quantify a specific analyte is growing. Owing to their special luminescence properties, lanthanide(III) cations offer attractive opportunities for the design of dual-color ratiometric probes. Here, the design principle of hetero-bis-lanthanide peptide conjugates by using native chemical ligation is described for perfect control of the localization of each lanthanide cation within the molecule. Two zinc-responsive probes, r-LZF1^Tb|Cs124|Eu and r-LZF1^Eu|Cs124|Tb are described on the basis of a zinc finger peptide and two DOTA (DOTA=1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid) complexes of terbium and europium. Both display dual-color ratiometric emission in response to the presence of Zn²⁺. By using a screening approach, anthracene was identified for the sensitization of the luminescence of two near-infrared-emitting lanthanides, Yb³⁺ and Nd³⁺. Thus, two novel zinc-responsive hetero-bis-lanthanide probes, r-LZF3^Yb|Anthra|Nd and r-LZF3^Nd|Anthra|Yb were assembled, the former offering a neat ratiometric response to Zn²⁺ with emission in the near-infrared around 1000 nm, which is unprecedented.     

Synthesis of peptide conjugated chelator oligomers for endoradiotherapy and MRT imaging

The clinical impact of peptides that accumulate in tumours is determined by the number of particle emitting or paramagnetic isotopes attached. Therefore, attempts should be made to increase the cargo capacity of the peptide carriers. A general synthetic route to conjugates is described that allows insertion of multiple DOTA (1,4,7,10-tetraazacyclododecane-N′,N″,N^?,N?-tetraacetic acid) moieties at the N-terminal end of the cyclic peptide Tyr³-octreotate. The peptide moiety was assembled by Fmoc solid phase synthesis and oxidised to form the cyclic disulfide. Subsequently, the required number of DOTA-tris tert-butyl ester chelating units were attached to the side chains of lysines. The conjugates were purified and thoroughly studied by RP-HPLC, size exclusion HPLC and mass spectrometry. The labelling of the novel conjugates and of DOTA⁰-Tyr³-octreotate (DOTATATE) was exemplified for ⁹⁰Y and ¹¹¹In. The methodology described here allows the versatile introduction of multiple DOTA chelates into a peptide sequence, thus, introducing a new scope to the receptor affine peptides that can be synthesised using solid phase synthesis.     

Optical Activity in the Near‐IR Region: The λ=980 nm Multiplet of Chiral Yb3+ Complexes

We used a very simplified electrostatic model based on charge and polarizability of atoms and groups on an organic ligand around a lanthanide ion to predict the near‐infrared electronic circular dichroism (NIR ECD) spectra of Yb³⁺ (a monoelectronic ion). We tuned our method by using two widely different complexes. The first was the heterobimetallic species CsYb(hfbc)₄ [hfbc=(?)‐3‐heptafluorobutyrylcamphorate], in which the ligand is a diketonate and, as such, is endowed with a chromophore with strong UV absorption (π–π^*). Its oxygen atoms define a square antiprism, which provides a symmetric coordination polyhedron. The second system was Yb DOTMA [DOTMA=(1R,4R,7R,10R)‐α,α′,α′′,α′′′‐tetramethyl‐1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid], a chiral Yb analogue of Gd DOTA (DOTA=1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid), in which the ligand lacks relevant electronic transitions and provides a dissymmetric cage. The relative weights of dynamic (ligand polarization) and static contributions to Yb NIR ECD were evaluated, and the spectra appear to have been well predicted by theory through the introduction of a heuristic weight factor. To validate the approach and to confirm the value of the weight factor, we applied it to two other compounds, namely, Na₃Yb(BINOLate)₃ and Yb(BINOLAM)₃ [BINOLate=2,2′‐dihydroxy‐1,1′‐binaphthyl; BINOLAM=3,3′‐bis(diethylaminomethyl)‐1‐1′‐bi‐2‐naphthol].     

Synthesis and Characterization of α-Hexadecyl-DOTA and its Gd（Ⅲ） Chelate

Synthesis and characterization of the ligand, 10-(α-hexadecylcarboxymethyl)- 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (H4L), and its Gd(Ⅲ) chelate are described. Protonation constants for H4L ( lg Ki^H = 10.52, 9.45,4.74, 4.10) and the stability constant for GdL^-(lg KGdL^-=24.50) were determined by potentiometric titrations.The results obtained show that the ligand still maintains the strong chelating properties of the parent DOTA(1,4,7,10-tetraazacyclododecane-N,N‘,N“N′“-tetraacetic acid) after introduction of a linear chain hexadecyl group at the acetic side chain of DOTA, and its basicity is not significantly altered.     

On the Aqueous Chemistry of the UIV–DOTA Complex

The 1,4,7,10-tetrazacyclodecane-1,4,7,10-tetraacetic acid (DOTA) aqueous complex of U^IV with H₂O, OH⁻, and F⁻ as axial ligands was studied by using UV/Vis spectrophotometry, ESI-MS, NMR spectroscopy, X-ray crystallography, and electrochemistry. The U^IV–DOTA complex with either water or fluoride as axial ligands was found to be inert to oxidation by molecular oxygen, whereas the complex with hydroxide as an axial ligand slowly hydrolyzed and was oxidized by dioxygen to a diuranate precipitate. The combined data set acquired shows that, although axial substitution of fluoride and hydroxide ligands instead of water does not seem to significantly change the aqueous DOTA complex structure, it has an important effect on the electronic configuration of the complex. The U^IV/U^III redox couple was found to be quasi-reversible for the complex with both axially bonded H₂O and hydroxide, but irreversible for the complex with axially bonded fluoride. Intriguingly, binding of the axial fluoride renders the irreversible one-electron U^V/U^IV oxidation of the [U^IV(DOTA)(H₂O)] complex quasi-reversible, which suggests the formation of the short-lived pentavalent form of the complex, an aqueous non-uranyl chelated U^V cation.     

Interactions and Encapsulation of Vitamins C,B3, and B6 with Dendrimers in Water

Titrations of commercial diaminobutane (DAB) and polyamidoamine (PAMAM) dendrimers by vitamins C (ascorbic acid, AA), B₃ (nicotinic acid), and B₆ (pyridoxine) were monitored by ¹H NMR spectroscopy using the chemical shifts of both dendrimer and vitamin protons and analyzed by comparison with the titration of propylamine. Quaternarizations of the terminal primary amino groups and intradendritic tertiary amino groups, which are nearly quantitative with vitamin C, were characterized by more or less sharp variations (Δδ) of the ¹H chemical shift (δ) at the equivalence points. The peripheral primary amino groups of the DAB dendrimers were quaternarized first, but not selectively, whereas a sharp chemical‐shift variation was recorded for the inner methylene protons near the tertiary amines, thereby indicating encapsulation, when all the dendritic amines were quaternarized. With DAB‐G5‐64‐NH₂, some excess acid is required to protonate the inner amino groups, presumably because of basicity decrease due to excess charge repulsion. On the other hand, this selectivity was not observed with PAMAM dendrimers. The special case of the titration of the dendrimers by vitamin B₆ indicates only dominant supramolecular hydrogen‐bonding interactions and no quaternarization, with core amino groups being privileged, which indicates the strong tendency to encapsulate vitamins. With vitamin B₃, a carboxylic acid, titration of DAB‐G3‐16‐NH₂ shows that only six peripheral amino groups are protonated on average, even with excess vitamin B₃, because protonation is all the more difficult due to increased charge repulsion, as positive charges accumulate around the dendrimer. Inner amino groups interact with this vitamin, however, thus indicating encapsulation presumably with supramolecular hydrogen bonding without much charge transfer.     

Novel ultrafiltration membranes with the least fouling properties for the treatment of veterinary antibiotics in the pharmaceutical wastewater

Dendrimers have received more attention in all fields of research these days. In the present study, polyamidoamine (PAMAM) dendrimers were synthesized on the acrylic ultrafiltration membranes to minimize fouling as an important deficiency in the separation process. The antifouling activity of these dendrimers with different generations (G0‐3) was tested to restrict three macrolides (tylvalosin, tylosin, and tulathromycin) and two pleuromutilins (tiamulin and valnemulin) as veterinary antibiotic drugs with amine groups and positive charges at pH = 7 of the membrane surface. These compounds are risky for human consumption. Due to having several amine functional groups and branches, PAMAM dendrimers can be a great coating agent for antifouling. G3 PAMAM dendrimer‐coated membranes had the best performance (water flux: 130.7 L/m²·h, rejection of tulathromycin: 91.4%, flux recovery ratio: 86.3%). The function of this ultrafiltration process depended on pore size and also charge surface. A significant reduction for irreversible and reversible fouling was observed for this new ultrafiltration membrane (F_ir: 14.5%, F_re: 21.9%). This observation was confirmed by the power law model. Three 5‐hour cycle ultrafiltration processes were carried out for veterinary antibiotic wastewater that showed 3.18% loss of initial water flux (for the third cycle), final cleaning efficiency of 96.82%, and tylvalosin rejection of 94.1%.     

Multiple‐Frequency and Variable‐Temperature EPR Study of Gadolinium(III) Complexes with Polyaminocarboxylates: Analysis and Comparison of the Magnetically Dilute Powder and the Frozen‐Solution Spectra

An electron paramagnetic resonance (EPR) study of glasses and magnetically dilute powders of [Gd(DTPA)(H₂O)]^2?, [Gd(DOTA)(H₂O)]^?, and macromolecular gadolinate(1?) complexes P792 was carried out at the X‐ and Q‐bands and at 240 GHz (DTPA=diethylenetriaminepentaacetato; DOTA=1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetato). The results show that the zero‐field splitting (ZFS) parameters for these complexes are quite different in a powder as compared to the frozen aqueous solution. In several complexes, an inversion of the sign of the axial component D of the zero field splitting is observed, indicating a significant structural change. In contrary to what was expected, powder samples obtained by lyophilization do not allow a more precise determination of the static ZFS parameters. The results obtained in glasses are more relevant to the problem of electron spin relaxation in aqueous solution than those obtained from powders.     

Synthesis of perfluorinated analogs of DOTA and NOTA: bifunctional chelating groups with potential applications in hybrid molecular imaging

The synthesis of novel NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelating groups bearing perfluorinated appendages is described. DOTA and NOTA groups are used in the production of radiopharmaceutical agents for PET and SPECT imaging (by chelation of radioactive metal ions), as well as MRI contrast agents (by chelation of lanthanide Ln³⁺ ions). The novel perfluorinated variants disclosed herein will enhance the synthesis and purification of such agents, as they are compatible with fluorous purification strategies. Moreover, the perfluorous tag is anticipated to be detectable by ¹⁹F-MRI, suggesting future applications in hybrid molecular imaging such as PET–MRI.     

Oxidative Conversion of a Europium(II)‐Based T1 Agent into a Europium(III)‐Based paraCEST Agent that can be Detected In Vivo by Magnetic Resonance Imaging

The Eu^II complex of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) tetra(glycinate) has a higher reduction potential than most Eu^II chelates reported to date. The reduced Eu^II form acts as an efficient water proton T₁ relaxation reagent, while the Eu^III form acts as a water‐based chemical exchange saturation transfer (CEST) agent. The complex has extremely fast water exchange rate. Oxidation to the corresponding Eu^III complex yields a well‐defined signal from the paraCEST agent. The time course of oxidation was studied in vitro and in vivo by T₁‐weighted and CEST imaging.     

Modular Synthesis of DOTA-Metal-Based PSMA-Targeted Imaging Agents for MRI and PET of Prostate Cancer

A practical, convergent synthesis of prostate-specific membrane antigen (PSMA) targeted imaging agents for MRI, PET, and SPECT of prostate cancer has been developed. In this approach, metals chelated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were placed on the side chains of lysine early in the synthesis to form imaging modules. These are coupled to targeting modules, in this case consisting of the PSMA-binding urea DCL, bonded to an activated linker. The modular approach to targeted molecular imaging agents (TMIAs) offers distinct advantages. By chelating the MRI contrast metal Gd early, it doubles as a protecting group for DOTA. Standard coupling and deprotection steps may be utilized to assemble the modules into peptides, and the need for tri-tert-butyl protection of DOTA requiring removal by strong acid is averted. This enables mild conjugation of the imaging module to a wide variety of targeting agents in the final step. It was further discovered that two labile metals, La³⁺ or Ce³⁺, can be used as placeholders in DOTA during the synthesis, then transmetalated in mild acid by Cu²⁺, Ga³⁺, In³⁺, and Y³⁺, metals used in PET/SPECT. This enables the efficient synthesis of nonradioactive analogues of targeted molecular imaging agents that may be transported or stored until needed. A simple and mild two-step transmetalation, involving de-metalation in dilute acid, followed by rapid chelation of the radioactive metal, may be conveniently performed later at the clinic to provide the TMIAs for PET or SPECT.     

Development of [<Superscript>64</Superscript>Cu]-DOTA-anti-CD20 for targeted therapy

Copper-64 was produced as a by-product of ⁵⁵Co via ⁶⁴Ni(p,n)⁶⁴Cu by 15 MeV proton bombardment of ^natNi resulting in a thick target yield of 5.31 MBq/μAh (143.5 μCi/μAh) and a radiochemical separation yield of 95% (radionuclide purity >97% after 25 hours of bombardment). Rituximab was successively labeled with [⁶⁴Cu]-CuCl₂. N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 °C using DOTA and N-hydroxy succinimide (NHS) in CH₂Cl₂ followed by the addition of 1 ml of a Rituximab pharmaceutical solution. Radiolabeling was performed at 37 °C in 3 hours. Radio thin-layer chromatography showed an overall radiochemical purity of 90–95% at optimized conditions (specific activity=30 GBq/mg, labeling efficacy; 82%) using various chromatography systems. The final isotonic ⁶⁴Cu-DOTA-Rituximab complex was passed through a 0.22 μm filter and checked by gel electrophoresis for radiolysis control. Stability of the final product was checked in the formulation and in presence of human serum at 37 °C.     

Colorimetric Determination of Polyamidoamine Dendrimers and their Derivates using a Simple and Rapid Ninhydrin Assay

Abstract

A simple, accurate and rapid colorimetric method using ninhydrin reagent was developed for the determination of polyamidoamine (PAMAM) dendrimers (G4, G5, and G6) and their derivates in aqueous medium. This method was based on the interaction of the primary amino group of PAMAM dendrimers with ninhydrin reagent to form a blue‐colored product with λ_max at 570 nm. Beer's law was obeyed in the concentration range of 25–200 µg/ml of all the three investigated PAMAM dendrimers. The effects of experimental parameters such as reagent concentration and reaction time were studied to optimize the colorimetric method. Accuracy and precision of the colorimetric method were assessed by statistical analysis. Acetylated G5 PAMAM dendrimers with various acetylated rates were simultaneously measured by the described ninhydrin assay and NMR studies and the data obtained by the two methods approximately accorded with each other. Results showed that the suggested procedures were suitable for the determination of PAMAM dendrimers and their derivates in aqueous solutions with satisfactory accuracy and precision.     

Thermodynamic and Kinetic Study of Scandium(III) Complexes of DTPA and DOTA: A Step Toward Scandium Radiopharmaceuticals

Diethylenetriamine‐N,N,N′,N′′,N′′‐pentaacetic acid (DTPA) and 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) scandium(III) complexes were investigated in the solution and solid state. Three ⁴⁵Sc NMR spectroscopic references suitable for aqueous solutions were suggested: 0.1 M Sc(ClO₄)₃ in 1 M aq. HClO₄ (δ_Sc=0.0 ppm), 0.1 M ScCl₃ in 1 M aq. HCl (δ_Sc=1.75 ppm) and 0.01 M [Sc(ox)₄]^5? (ox^2?=oxalato) in 1 M aq. K₂C₂O₄ (δ_Sc=8.31 ppm). In solution, [Sc(dtpa)]^2? complex (δ_Sc=83 ppm, ?ν=770 Hz) has a rather symmetric ligand field unlike highly unsymmetrical donor atom arrangement in [Sc(dota)]^? anion (δ_Sc=100 ppm, ?ν=4300 Hz). The solid‐state structure of K₈[Sc₂(ox)₇] ? 13 H₂O contains two [Sc(ox)₃]^3? units bridged by twice “side‐on” coordinated oxalate anion with Sc³⁺ ion in a dodecahedral O₈ arrangement. Structures of [Sc(dtpa)]^2? and [Sc(dota)]^? in [(Hguanidine)]₂[Sc(dtpa)] ? 3 H₂O and K[Sc(dota)][H₆dota]Cl₂ ? 4 H₂O, respectively, are analogous to those of trivalent lanthanide complexes with the same ligands. The [Sc(dota)]^? unit exhibits twisted square‐antiprismatic arrangement without an axial ligand (TSA′ isomer) and [Sc(dota)]^? and (H₆dota)²⁺ units are bridged by a K⁺ cation. A surprisingly high value of the last DOTA dissociation constant (pK_a=12.9) was determined by potentiometry and confirmed by using NMR spectroscopy. Stability constants of scandium(III) complexes (log K_ScL 27.43 and 30.79 for DTPA and DOTA, respectively) were determined from potentiometric and ⁴⁵Sc NMR spectroscopic data. Both complexes are fully formed even below pH 2. Complexation of DOTA with the Sc³⁺ ion is much faster than with trivalent lanthanides. Proton‐assisted decomplexation of the [Sc(dota)]^? complex (τ_1/2=45 h; 1 M aq. HCl, 25 °C) is much slower than that for [Ln(dota)]^? complexes. Therefore, DOTA and its derivatives seem to be very suitable ligands for scandium radioisotopes.     

Determination of maximum loading capacity of polyamidoamine (PAMAM) dendrimers and evaluation of Cu55 dendrimer‐encapsulated nanoparticles for catalytic activity

Spectrophotometric titrations provide information about the interior of the polyamidoamine (PAMAM) dendrimers, and therefore how nanoparticles are encapsulated. In this work, binding studies were performed to determine maximum loading capacities (N) of hydroxyl terminated G4, G5, and G6 PAMAM dendrimers with Cu²⁺ ions. The values of N found via spectrophotometric titrations were 16.22, 31.86, and 57.36 for G4‐OH, G5‐OH, and G6‐OH, respectively. The determination of loading capacity was also done using Viva spin filtration, and the results were found to be in agreement with those found via spectrophotometric titrations. From the binding isotherm, the values of equilibrium constant (K′) were determined and found to be 0.0488 (G4‐OH), 0.0291 (G5‐OH), and 0.0158 (G6‐OH). Owing to instability of G4‐OH (Cu₁₆), G5‐OH (Cu₃₂), and G6‐OH (Cu₅₇) dendrimer‐encapsulated nanoparticles (DENs) synthesized, G6‐OH (Cu₅₅) DENs of average size 2.6 ± 0.3 nm were prepared and were found to be relatively stable. Thus G6‐OH (Cu₅₅) catalyst was evaluated for the reduction of 4‐nitrophenol and was found to be catalytically active toward reduction of 4‐nitrophenol. Reaction kinetics of 4NP reduction was thoroughly studied in light of the Langmuir‐Hinshelwood kinetic model, and surface rate k, and the adsorption rates K_4NP, and K_BH4 were determined. The reaction was performed at different temperatures, which further expanded the study into determination of thermodynamic (ΔH^‡, ΔS^‡, ΔG^‡, and E_A) parameters.     

Evaluation of different PAMAM dendrimers as molecular vehicle of 1,2,4-triazine N-oxide derivative with potential antitumor activity

The interaction between a 1,2,4-triazine N-oxide derivative, that holds potential antitumor activity under hypoxic conditions, and diverse polyamidoamine (PAMAM) dendrimers were investigated with the purpose of select the most appropriate macromolecule to act as potential molecular carrier of this active compound. The results shows that dendrimers with amine terminal groups (PAMAM-AT G = 3) and dendrimers with carboxylate terminal groups (PAMAM-CT G2.5 and G4.5) produces triazine derivative hydrolysis, even in buffered medium, and are not suitable as carriers. In contrast, dendrimers with neutral end groups (PAMAM-OHT) shows stable association with the active compound, making this dendrimer a possible medium for triazine carriage.     

Synthesis of P(MBA-co-MAA) microsphere-grafted PAMAM dendrimers and their application as supporters for gold nanoparticles

Poly(N,N′-methylenebisacrylamide-co-acrylic acid) microsphere-supported polyamidoamine (PAMAM) dendrimers up to third generation (G) were grown onto the surface as well as the gel-layer of P(MBA-co-MAA) microspheres by a divergent method. The P(MBA-co-MAA) supported PAMAM dendrimers were used as heterogeneous stabilizers for the gold nanoparticles by an in situ reduction of HAuCl₄ via the efficient coordination interaction between the amino groups of the supported PAMAM dendrimers and the gold atoms. The effects of the generations of the P(MBA-co-MAA) supported PAMAM dendrimer on the loadings and the catalytic activity of the heterogeneous Au nanoparticles were systematically investigated with the reduction of 4-nitrophenol to 4-aminophenol as a model reaction.