NMR Characterization of PAMAM_G5.NH₂ Entrapped Atomic and Molecular Assemblies

High resolution NMR spectroscopy, NMR diffusiometry, and NMR cryoporometry have been used to investigate aqueous solution (D₂O) of PAMAM_G5.NH₂-(Au)_25–100 and PAMAM_G5.NH₂-(H₂O)₁₀₀₀–(H₂O)₄₀₀₀ systems. In the case of dendrimer entrapped gold nanoparticles, the detailed analysis of high resolution NMR spectra has shown that no precursor complex formation happens under the circumstances applied for reduction. Further PGSE results verify that gold nanoparticles of 1.9–2.6 nm size are entrapped in the outermost part of the dendrimers and probably more than one dendrimer molecule takes part in the stabilization process. This system looks like a transition state between dendrimer encapsulated nanoparticles (DENs) and dendrimer stabilized nanoparticles (DSNs), and we deal with it in details for what this means. NMR cryoporometry experiments were performed to detect the encapsulation of water molecules. The results show that, in the swelling PAMAM_G5.NH₂ dendrimers, by adding water step by step, there are specific cavities for water with diameters of 3.6 and 5.2 nm. These cavities have a penetrable wall for water molecules and probably exist very close to the terminal groups. The permeability of the cavities is increasing with the increase of the water content. In dilute solution, the formation of nanoparticles is determined by the ratio of the rate of nucleation and aggregation and the latter is affected by the PAMAM_G5.NH₂

Impact of Dendrimer Surface Functional Groups on the Release of Doxorubicin from Dendrimer Carriers

Generation 5 (G5) poly­(amidoamine) dendrimers with acetyl (G5.NHAc), glycidol hydroxyl (G5.NGlyOH), and succinamic acid (G5.SAH) terminal groups were used to physically encapsulate an anticancer drug doxorubicin (DOX). Both UV–vis spectroscopy and multiple NMR techniques including one-dimensional NMR and two-dimensional NMR were applied to investigate the interactions between different dendrimers and DOX. The influence of the surface functional groups of G5 dendrimers on the DOX encapsulation, release kinetics, and cancer cell inhibition effect was investigated. We show that all three types of dendrimers are able to effectively encapsulate DOX and display therapeutic inhibition effect to cancer cells, which is solely associated with the loaded DOX. The relatively stronger interactions of G5.NHAc or G5.NGlyOH dendrimers with DOX than that of G5.SAH dendrimers with DOX demonstrated by NMR techniques correlate well with the slow release rate of DOX from G5.NHAc/DOX or G5.NGlyOH/DOX complexes. In contrast, the demonstrated weak interaction between G5.SAH and DOX causes a fast release of DOX, suggesting that the G5.SAH/DOX complex may not be a proper option for further <i>in vivo</i> research. Our findings suggest that the dendrimer surface functional groups are crucial for further design of multifunctional dendrimer-based drug delivery systems for various biomedical applications

[Tl^III(dota)]⁻: An Extraordinarily Robust Macrocyclic Complex

The X-ray structure of {C­(NH₂)₃}­[Tl­(dota)]·H₂O shows that the Tl³⁺ ion is deeply buried in the macrocyclic cavity of the dota^4– ligand (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) with average Tl–N and Tl–O distances of 2.464 and 2.365 Å, respectively. The metal ion is directly coordinated to the eight donor atoms of the ligand, which results in a twisted square antiprismatic (TSAP′) coordination around Tl³⁺. A multinuclear ¹H, ¹³C, and ²⁰⁵Tl NMR study combined with DFT calculations confirmed the TSAP′ structure of the complex in aqueous solution, which exists as the Λ­(λλλλ)/Δ­(δδδδ) enantiomeric pair. ²⁰⁵Tl NMR spectroscopy allowed the protonation constant associated with the protonation of the complex according to [Tl­(dota)]⁻ + H⁺ ⇆ [Tl­(Hdota)] to be determined, which turned out to be p<i>K</i>^H_Tl(dota) = 1.4 ± 0.1. [Tl­(dota)]⁻ does not react with Br^–, even when using an excess of the anion, but it forms a weak mixed complex with cyanide, [Tl­(dota)]⁻ + CN^– ⇆ [Tl­(dota)­(CN)]^2–, with an equilibrium constant of <i>K</i>_mix = 6.0 ± 0.8. The dissociation of the [Tl­(dota)]⁻ complex was determined by UV–vis spectrophotometry under acidic conditions using a large excess of Br^–, and it was found to follow proton-assisted kinetics and to take place very slowly (∼10 days), even in 1 M HClO₄, with the estimated half-life of the process being in the 10⁹ h range at neutral pH. The solution dynamics of [Tl­(dota)]⁻ were investigated using ¹³C NMR spectroscopy and DFT calculations. The ¹³C NMR spectra recorded at low temperature (272 K) point to <i>C</i>₄ symmetry of the complex in solution, which averages to <i>C</i>_4<i>v</i> as the temperature increases. This dynamic behavior was attributed to the Λ­(λλλλ) ↔ Δ­(δδδδ) enantiomerization process, which involves both the inversion of the macrocyclic unit and the rotation of the pendant arms. According to our calculations, the arm-rotation process limits the Λ­(λλλλ) ↔ Δ­(δδδδ) interconversion

Dithallium(III)-Containing 30-Tungsto-4-phosphate, [Tl₂Na₂(H₂O)₂(P₂W₁₅O₅₆)₂]^16–: Synthesis, Structural Characterization, and Biological Studies

Here we report on the synthesis and structural characterization of the dithallium­(III)-containing 30-tungsto<i>-</i>4-phosphate [Tl₂Na₂(H₂O)₂­{P₂W₁₅O₅₆}₂]^16– (<b>1</b>) by a multitude of solid-state and solution techniques. Polyanion <b>1</b> comprises two octahedrally coordinated Tl³⁺ ions sandwiched between two trilacunary {P₂W₁₅} Wells–Dawson fragments and represents only the second structurally characterized, discrete thallium-containing polyoxometalate to date. The two outer positions of the central rhombus are occupied by sodium ions. The title polyanion is solution-stable as shown by ³¹P and ^203/205Tl NMR. This was also supported by Tl NMR spectra simulations including several spin systems of isotopologues with half-spin nuclei (²⁰³Tl, ²⁰⁵Tl, ³¹P, ¹⁸³W). ²³Na NMR showed a time-averaged signal of the Na⁺ counter cations and the structurally bonded Na⁺ ions. ^203/205Tl NMR spectra also showed a minor signal tentatively attributed to the trithallium-containing derivative [Tl₃Na­(H₂O)₂­(P₂W₁₅O₅₆)₂]^14–, which could also be identified in the solid state by single-crystal X-ray diffraction. The bioactivity of polyanion <b>1</b> was also tested against bacteria and <i>Leishmania</i>