Multi-Technique Characterization of Poly-L-lysine Dendrigrafts-Cu(II) Complexes for Biocatalysis

Abstract

Poly-L-lysine is a biocompatible polymer used for drug or gene delivery, for transport through cellular membranes, and as nanosized magnetic resonance imaging contrast agents. Cu(II)-poly-L-lysine complexes are of particular interest for their role in biocatalysis. In this study, poly-L-lysine dendrigrafts (DGLs) at different generations (G2, G3, and G4) are synthesized and characterized in absence and presence of Cu(II) by means of electron paramagnetic resonance (EPR), UV-Vis, potentiometric titration and circular dichroism (CD). The analysis is performed as a function of the [Cu(II)]/[Lys] (=R) molar ratio, pH and generation by identifying differently flexible complexes in different dendrimer regions. The amine sites in the lateral chains become increasingly involved with the increase of pH. The good agreement and complementarity of the results from the different techniques provide an integrate view of the structural and dynamic properties of Cu(II)-DGL complexes implementing their use as biocatalysts.

Fine-Tuning the Interaction and Therapeutic Effect of Cu(II) Carbosilane Metallodendrimers in Cancer Cells: An In Vitro Electron Paramagnetic Resonance Study

“…The magnetic parameters from computation (the computed line, in red, is also shown in Figure S1) of the fast component of dendrimer 2 in RPMI, ⟨A⟩ ≥ 69 G and ⟨g⟩ ≥ 2.123, compared with literature ones, ,− ,− indicate the formation of a square planar (orthorhombically distorted) Cu­(II)-N 4 coordination. The nitrogen sites are the iminopyridine groups at the dendrimer surface, and nitrogen sites present in the RPMI medium are listed above.…”

“…For an axial symmetry, where g zz and A zz are the largest values, the z molecular axis corresponds to the main direction of the orbital containing the unpaired electron. The magnetic g ii and A ii components were compared with values found in previous literature in order to extract information about ,− ,− (i) the type of coordination in Cu­(II) complexes (such as the number of oxygen and nitrogen ligands); (ii) the geometry of the Cu­(II) complex; and (iii) the strength of the coordinating bonds. In detail, an increase in the A ii values (mainly A zz , but, for clarity, the average value ⟨A⟩ = (A xx + A yy + A zz )/3 was calculated and compared between spectra) and a decrease in the g ii values (mainly g xx was clearly evaluable in all our spectra) are usually reflected in an increased number of nitrogen ligands and/or by a stronger interaction; (b) the correlation time for the rotational motion (τ) that provides information about the flexibility and coordination strength of the dendrimer branches by measuring the mobility of the complex; an increase of τ reveals an increase of the microviscosity at the Cu­(II) site and, consequently, a decreased in mobility.…”

“…The EPR study provided dynamical and structural information on the in vitro behavior of the metallodendrimers in both healthy and tumor cells. This technique has already demonstrated to be a powerful tool to characterize Cu­(II) dendrimer complexes. ,− Finally, the intracellular trafficking and mechanism of action of the Cu­(II) carbosilane dendrimer complexes to be used as anticancer drugs was evaluated by means of various biological tests, including cytotoxicity, alteration of mitochondria membrane potential, and autophagy flux.…”

Highly Branched Polymers Based on Poly(amino acid)s for Biomedical Application

“…More recently, highly branched PAAs gained attention for their ability to (i) mimic globular proteins, so called ‘proteinoids’, which can be studied as mock proteins or peptides for their interaction with various environments [ 6 , 7 , 8 , 9 ] and were mentioned as early as 1958 in this capacity by Fox and Harada [ 10 ], and (ii) interact with biologically relevant molecules. The latter one has become the more intensely researched area as PAAs lend themselves to a multitude of biomedical applications, including the delivery of drugs [ 11 , 12 , 13 ] and nucleotides, for a review see Kataoka [ 14 ], and as imaging reagents, [ 15 , 16 ] and tissue adhesives [ 17 , 18 ] and most recently in the development of theranostics [ 19 , 20 ].…”

Everything You Always Wanted to Know about Poly‐l‐lysine Dendrigrafts (But Were Afraid to Ask)

“…All reactionsfor arm and core modificationso ft he native DGLs reported in the literature so far.Auniquee xample of introduced motif per type of reaction is showed here (with the corresponding references[20][21][22][23][24][25]). …”