Comprehensive vibrational spectroscopic investigation of trans,trans,trans-[Pt(N3)2(OH)2(py)2], a Pt(IV) diazido anticancer prodrug candidate

We report a detailed study of a promising photoactivatable metal-based anticancer prodrug candidate, trans,trans,trans-[Pt(N3)2(OH)2(py)2] (C1; py = pyridine), using vibrational spectroscopic techniques. Attenuated total reflection Fourier transform infrared (ATR-FTIR), Raman, and synchrotron radiation far-IR (SR-FIR) spectroscopies were applied to obtain highly resolved ligand and Pt-ligand vibrations for C1 and its precursors (trans-[Pt(N3)2(py)2] (C2) and trans-[PtCl2(py)2] (C3)). Distinct IR- and Raman-active vibrational modes were assigned with the aid of density functional theory calculations, and trends in the frequency shifts as a function of changing Pt coordination environment were determined and detailed for the first time. The data provide the ligand and Pt-ligand (azide, hydroxide, pyridine) vibrational signatures for C1 in the mid- and far-IR region, which will provide a basis for the better understanding of the interaction of C1 with biomolecules

Dendrimers as Nd3+ ligands: Effect of Generation on the Efficiency of the Sensitized Lanthanide Emission

We have designed two novel dendrimers with cyclam cores with appended poly(amido amine) (PAMAM) dendrons, decorated at the periphery with four and eight dansyl chromophores, respectively. The photophysical properties of the dendrimers and their Nd3+ complexes have been investigated. The energy-transfer efficiency to the lanthanide ions from these dendrimers has been studied as a function of the generation. It has been observed that an increase in the dendrimer generation as well as the number of amide units enhances the energy transfer to the lanthanide ion

Facile preparation of multifunctionalisable 'stealth' upconverting nanoparticles for biomedical applications

Pure hexagonal (β-phase) NaYF4-based hydrophobic upconverting nanoparticles (UCNPs) were surface-modified with O-phospho-l-threonine (OPLT), alendronic acid, and PEG-phosphate ligands to generate water-dispersible UCNPs. Fourier-transform infrared (FTIR) spectroscopy was used to establish the presence of the ligands on the UCNP surface. These UCNPs exhibit great colloidal stability and a near-neutral surface at physiological pH, as confirmed by dynamic light scattering (DLS) and zeta potential (ζ) measurements, respectively. The particles also display excellent long-term stability, with no major adverse effect on the size of UCNPs when kept at pH 7.4. Upon exposure to human serum, PEG-phosphate- and alendronate-coated UCNPs showed no formation of biomolecular corona, as confirmed by SDS-PAGE analysis. The photophysical properties of water-dispersible UCNPs were investigated using steady-state as well as time-resolved luminescence spectroscopy, under excitation at ca. 800 nm. The results clearly show that the UCNPs demonstrate bright upconversion (UC) luminescence. Furthermore, the presence of reactive groups on the NPs, such as free amine groups in alendronate-coated UCNPs, enables further functionalisation of UCNPs with, for example, small molecules, peptides, proteins, and antibodies. Overall these protein corona resistant UCNPs show great biocompatibility and are worthy of further investigation as potential new biomaging probes

Amyloid aggregation and membrane activity of the antimicrobial peptide uperin 3.5

Amyloid fibrils are highly ordered, b-sheet rich forms of aggregated peptides and proteins that are associated with a variety of pathological human disorders, including Alzheimer’s and Parkinson’s diseases. Amyloid fibril-forming peptides may be functionally related to antimicrobial peptides, despite differing significantly in sequence and structure. Specifically, their interaction with lipid membranes has mechanistic similarities. The 17-amino acid peptide uperin 3.5 (U3.5) from an Australian amphibian is antimicrobial and amyloidogenic. Using a quartz crystal microbalance, we investigated the interaction of U3.5 with artificial membranes and found that (i) the membrane interaction of U3.5 is independent of the peptide’s aggregation state, (ii) the presence of cholesterol in the membrane dramatically alters peptide–membrane interaction leading to a transmembrane pore-like arrangement of U3.5, and (iii) electrostatic interaction is important for the membrane activity of U3.5 whereby removal of the positive charge at position 7 of U3.5 enhanced its fibrillar aggregation and ablated its membrane interaction, i.e. there is an inverse relationship between the antimicrobial and amyloidogenic properties of U3.5.Lisandra L. Martin, Clemens Kubeil, Stefania Piantavigna, Tarun Tikkoo, Nicholas P. Gray, Torsten John, Antonio N. Calabrese, Yanqin Liu, Yuning Hong, Mohammed A. Hossain, Nitin Patil, Bernd Abel, Ralf Hoffmann, John H. Bowie, John A. Carve