Due to their unique photophysical properties, upconverting nanoparticles (UCNPs), i. e. particles capable of converting near-infrared (NIR) photons into tunable emissions in the range of ultraviolet (UV) to NIR, have great potential for use in various biomedical fields such as bioimaging, photodynamic therapy and bioanalytical applications.
View Article and Find Full Text PDFA photoactivatable ruthenium(II) carbonyl complex -[Ru(II)Cl(BisQ)(CO)]PF was prepared using a tridentate bisquinoline ligand (BisQ=(2,6-diquinolin-2-yl)pyridin). Compound was thoroughly characterized by standard analytical methods and single crystal X-ray diffraction. The crystal structure of the complex cation reveals a distorted octahedral geometry.
View Article and Find Full Text PDFWe demonstrate a novel strategy for preparing hydrophilic upconverting nanoparticles (UCNPs) by harnessing the photocrosslinking ability of diacetylenes. Replacement of the hydrophobic oleate coating on the UCNPs with 10,12-pentacosadiynoic acid, followed by overcoating with diacetylene phospholipid and subsequent photocrosslinking under 254 nm irradiation produces water-dispersible polydiacetylene-coated UCNPs. These UCNPs resist the formation of a biomolecular corona and show great colloidal stability.
View Article and Find Full Text PDF1,4,7-Triazacyclononane (TACN)-based mono- and poly-nuclear metal complexes have found extensive use as biological mimics for understanding the structural and operational aspects of complex natural systems. Their coordination flexibility has also provided researchers access to a vast library of radiometal-binding motifs that display excellent thermodynamic stability and kinetic inertness upon metal complexation. Synthetic modification of the TACN backbone has yielded ligands that can form metal complexes with coordination geometries well suited for these applications.
View Article and Find Full Text PDFPure hexagonal (β-phase) NaYF-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.
View Article and Find Full Text PDFWe report a simple one-pot method for the rapid preparation of sub-10 nm pure hexagonal (β-phase) NaYF-based upconverting nanoparticles (UCNPs). Using Therminol 66 as a co-solvent, monodisperse UCNPs could be obtained in unusually short reaction times. By varying the reaction time and reaction temperature, it was possible to control precisely the particle size and crystalline phase of the UCNPs.
View Article and Find Full Text PDFThe photodecomposition mechanism of trans,trans,trans-[Pt(N ) (OH) (py) ] (1, py=pyridine), an anticancer prodrug candidate, was probed using complementary Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR), transient electronic absorption, and UV/Vis spectroscopy. Data fitting using Principal Component Analysis (PCA) and Multi-Curve Resolution Alternating Least Squares, suggests the formation of a trans-[Pt(N )(py) (OH/H O)] intermediate and trans-[Pt(py) (OH/H O) ] as the final product upon 420 nm irradiation of 1 in water. Rapid disappearance of the hydroxido ligand stretching vibration upon irradiation is correlated with a -10 cm shift to the antisymmetric azido vibration, suggesting a possible second intermediate.
View Article and Find Full Text PDFPolyacrylic-acid-coated ultra-small super-paramagnetic iron oxide nanoparticles were surface-modified with low-molecular-weight sulfobetaines or 3-(diethylamino)propylamine in order to generate nanoparticles with zwitterionic character (ZW-NPs). The ZW-NPs proved highly resistant to serum protein corona formation in vitro, as revealed by atomic force microscopy, SDS-PAGE and proteomics analysis, and exhibited low cytotoxicity towards A431 and HEK293 cells. The presence of unreacted carboxylic acid groups enabled additional functionalization with fluorescent (Cy5) and radioactive [ Cu-dmptacn; dmptacn=1,4-bis(2-pyridinylmethyl)-1,4,7-triazacyclononane] moieties.
View Article and Find Full Text PDFWe 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.
View Article and Find Full Text PDFThree new conjugates featuring the aminoglycoside antibiotic neomycin B linked to the 1,4,7,10-tetraazacyclododecane (cyclen) macrocycle via alkyl chains of varying lengths were synthesized from suitably protected derivatives of these precursors via conventional peptide coupling protocols. The final products were characterized by H NMR spectroscopy, mass spectrometry, and elemental analysis. FRET-based measurements examining the ability of the compounds to displace coumarin-labelled kanamycin A or neomycin B from Dy547-labelled prokaryotic ribosomal A-site RNA revealed that they bind to the A-site with slightly higher affinities than the parent aminoglycoside (e.
View Article and Find Full Text PDFExamples of proteins that incorporate one or more metal ions within their structure are found within a broad range of classes, including oxidases, oxidoreductases, reductases, proteases, proton transport proteins, electron transfer/transport proteins, storage proteins, lyases, rusticyanins, metallochaperones, sporulation proteins, hydrolases, endopeptidases, luminescent proteins, iron transport proteins, oxygen storage/transport proteins, calcium binding proteins, and monooxygenases. The metal coordination environment therein is often generated from residues inherent to the protein, small exogenous molecules (e.g.
View Article and Find Full Text PDFThe rapid increase in multi-drug resistant bacteria has resulted in previously discontinued treatments being revisited. Aminoglycosides are effective "old" antibacterial agents that fall within this category. Despite extensive usage and understanding of their intracellular targets, there is limited mechanistic knowledge regarding how aminoglycosides penetrate bacterial membranes.
View Article and Find Full Text PDFA new Boc-protected 1,4,7-triazacyclononane (TACN)-based pro-chelator compound featuring a "clickable" azidomethylpyridine pendant has been developed as a building block for the construction of multimodal imaging agents. Conjugation to a model alkyne (propargyl alcohol), followed by deprotection, generates a pentadentate ligand, as confirmed by X-ray crystallographic analysis of the corresponding distorted square-pyramidal Cu(II) complex. The ligand exhibits rapid (64)Cu(II)-binding kinetics (>95% radiochemical yield in <5 min) and a high resistance to demetalation.
View Article and Find Full Text PDFRuthenium complexes are currently considered to be among the most promising alternatives to platinum anticancer drugs. In this work, thirteen structural analogues and organelle/receptor-targeting peptide bioconjugates of a cytotoxic bis(dppz)-Ru(II) complex [Ru(dppz)2 (CppH)](PF6 )2 (1) were prepared, characterized, and assessed for their cytotoxicity and cellular localization (CppH=2-(2'-pyridyl)pyrimidine-4-carboxylic acid; dppz=dipyrido[3,2-a:2',3'-c]phenazine). It was observed that structural modifications (lipophilicity, charge, and size-based) result in the cytotoxic potency of 1 being compromised.
View Article and Find Full Text PDFImproving the selectivity of anticancer drugs towards cancer cells is one of the main goals of drug optimization; the prodrug strategy has been one of the most promising. A light-triggered prodrug strategy is presented as an efficient approach for controlling cytotoxicity of the substitutionally inert cytotoxic complex [Ru(dppz)2(CppH)](PF6)2(C1; CppH=2-(2-pyridyl)pyrimidine-4-carboxylic acid; dppz=dipyrido[3,2-a:2',3'-c]phenazine). Attachment of a photolabile 3-(4,5-dimethoxy-2-nitrophenyl)-2-butyl (DMNPB) ester ("photocaging") makes the otherwise active complex C1 innocuous to both cancerous (HeLa and U2OS) and non-cancerous (MRC-5) cells.
View Article and Find Full Text PDFA series of ruthenium(II) dicarbonyl complexes of formula [RuCl2(L)(CO)2] (L = bpy(CH3,CH3) = 4,4'-dimethyl-2,2'-bipyridine, bpy(CH3,CHO) = 4'-methyl-2,2'-bipyridine-4-carboxyaldehyde, bpy(CH3,COOH) = 4'-methyl-2,2'-bipyridine-4-carboxylic acid, CppH = 2-(pyridin-2-yl)pyrimidine-4-carboxylic acid, dppzcH = dipyrido[3,2-a:2',3'-c]phenazine-11-carboxylic acid), and [RuCl(L)(CO)2](+) (L = tpy(COOH) = 6-(2,2':6',2″-terpyridine-4'-yloxy)hexanoic acid) has been synthesized. In addition, a high-yield synthesis of a peptide nucleic acid (PNA) monomer containing the 2-(pyridin-2-yl)pyrimidine ligand was also developed, and this compound was used to prepare the first Ru(II) dicarbonyl complex, [RuCl2(Cpp-L-PNA)(CO)2],(Cpp-L-PNA = tert-butyl-N-[2-(N-9-fluorenylmethoxycarbonyl)aminoethyl]-N-[6-(2-(pyridin-2-yl)pyrimidine-4-carboxamido)hexanoyl]glycinate) attached to a PNA monomer backbone. Such metal-complex PNA-bioconjugates are attracting profound interest for biosensing and biomedical applications.
View Article and Find Full Text PDFAs a proof-of-principle, two hetero-bimetallic PNA oligomers containing a ruthenium(II) polypyridyl and a cyclopentadienyl manganese tricarbonyl complex have been prepared by serial combination of solid-phase peptide coupling and in-solution thiol chemistry. Solid-phase N-terminus attachment of Ru(II)-polypyridyl carboxylic acid derivative, C1, onto the thiol-functionalized PNA backbone (H-a-a-g-t-c-t-g-c-linker-cys-NH 2) has been performed by standard peptide coupling method. As two parallel approaches, the strong affinity of thiols for maleimide and haloacetyl group has been exploited for subsequent post-SPPS addition of cymantrene-based organometallic cores, C2 and C3.
View Article and Find Full Text PDFA great majority of the Ru complexes currently studied in anticancer research exert their antiproliferative activity, at least partially, through ligand exchange. In recent years, however, coordinatively saturated and substitutionally inert polypyridyl Ru(II) compounds have emerged as potential anticancer drug candidates. In this work, we present the synthesis and detailed characterization of two novel inert Ru(II) complexes, namely, [Ru(bipy)(2)(Cpp-NH-Hex-COOH)](2+) (2) and [Ru(dppz)(2)(CppH)](2+) (3) (bipy = 2,2'-bipyridine; CppH = 2-(2'-pyridyl)pyrimidine-4-carboxylic acid; Cpp-NH-Hex-COOH = 6-(2-(pyridin-2-yl)pyrimidine-4-carboxamido)hexanoic acid; dppz = dipyrido[3,2-a:2',3'-c]phenazine).
View Article and Find Full Text PDFThe feasibility of devising a solid support mediated approach to multimodal Ru(II)-peptide nucleic acid (PNA) oligomers is explored. Three Ru(II)-PNA-like monomers, [Ru(bpy)(2)(Cpp-L-PNA-OH)](2+) (M1), [Ru(phen)(2)(Cpp-L-PNA-OH)](2+) (M2), and [Ru(dppz)(2)(Cpp-L-PNA-OH)](2+) (M3) (bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine, Cpp-L-PNA-OH = [2-(N-9-fluorenylmethoxycarbonyl)aminoethyl]-N-[6-(2-(pyridin-2yl)pyrimidine-4-carboxamido)hexanoyl]-glycine), have been synthesized as building blocks for Ru(II)-PNA oligomers and characterized by IR and (1)H NMR spectroscopy, mass spectrometry, electrochemistry and elemental analysis. As a proof of principle, M1 was incorporated on the solid phase within the PNA sequences H-g-c-a-a-t-a-a-a-a-Lys-NH(2) (PNA1) and H-P-K-K-K-R-K-V-g-c-a-a-t-a-a-a-a-lys-NH(2) (PNA4) to give PNA2 (H-g-c-a-a-t-a-a-a-a-M1-lys-NH(2)) and PNA3 (H-P-K-K-K-R-K-V-g-c-a-a-t-a-a-a-a-M1-lys-NH(2)), respectively.
View Article and Find Full Text PDFThree new metal-coordinating ligands, L(1)·4HCl [1-(2-guanidinoethyl)-1,4,7-triazacyclononane tetrahydrochloride], L(2)·4HCl [1-(3-guanidinopropyl)-1,4,7-triazacyclononane tetrahydrochloride], and L(3)·4HCl [1-(4-guanidinobutyl)-1,4,7-triazacyclononane tetrahydrochloride], have been prepared via the selective N-functionalization of 1,4,7-triazacyclononane (tacn) with ethylguanidine, propylguanidine, and butylguanidine pendants, respectively. Reaction of L(1)·4HCl with Cu(ClO(4))(2)·6H(2)O in basic aqueous solution led to the crystallization of a monohydroxo-bridged binuclear copper(II) complex, [Cu(2)L(1)(2)(μ-OH)](ClO(4))(3)·H(2)O (C1), while for L(2) and L(3), mononuclear complexes of composition [Cu(L(2)H)Cl(2)]Cl·(MeOH)(0.5)·(H(2)O)(0.
View Article and Find Full Text PDFA series of Ru(II)-peptide nucleic acid (PNA)-like monomers, [Ru(bpy)(2)(dpq-L-PNA-OH)](2+) (M1), [Ru(phen)(2)(dpq-L-PNA-OH)](2+) (M2), [Ru(bpy)(2)(dppz-L-PNA-OH)](2+) (M3), and [Ru(phen)(2)(dppz-L-PNA-OH)](2+) (M4) (bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, dpq-L-PNA-OH = 2-(N-(2-(((9H-fluoren-9-yl)methoxy)carbonylamino)ethyl)-6-(dipyrido[3,2-a:2',3'-c]phenazine-11-carboxamido)hexanamido)acetic acid, dppz-L-PNA-OH = 2-(N-(2-(((9H-fluoren-9-yl) methoxy)carbonylamino)ethyl)-6-(dipyrido[3,2-f:2',3'-h]quinoxaline-2-carboxamido)acetic acid) have been synthesized and characterized by IR and (1)H NMR spectroscopy, mass spectrometry, and elemental analysis. As is typical for Ru(II)-tris(diimine) complexes, acetonitrile solutions of these complexes (M1-M4) show MLCT transitions in the 443-455 nm region and emission maxima at 618, 613, 658, and 660 nm, respectively, upon photoexcitation at 450 nm. Changes in the ligand environment around the Ru(II) center are reflected in the luminescence and electrochemical response obtained from these monomers.
View Article and Find Full Text PDFThree new metal-coordinating ligands, L(1), L(2), and L(3), have been prepared by appending o-, m-, and p-xylylguanidine pendants, respectively, to one of the nitrogen atoms of 1,4,7-triazacyclononane (tacn). The copper(II) complexes of these ligands are able to accelerate cleavage of the P-O bonds within the model phosphodiesters bis(p-nitrophenyl)phosphate (BNPP) and [2-(hydroxypropyl)-p-nitrophenyl]phosphate (HPNPP), as well as supercoiled pBR 322 plasmid DNA. Their reactivity toward BNPP and HPNPP is not significantly different from that of the nonguanidinylated analogues, [Cu(tacn)(OH(2))(2)](2+) and [Cu(1-benzyl-tacn)(OH(2))(2)](2+), but they cleave plasmid DNA at considerably faster rates than either of these two complexes.
View Article and Find Full Text PDFTwo new ligands, L(1) and L(2), have been prepared via N-functionalization of 1,4,7-triazacyclononane (tacn) with pairs of ethyl- or propyl-guanidine pendants, respectively. The X-ray crystal structure of [CuL(1)](ClO4)2 (C1) isolated from basic solution (pH 9) indicates that a secondary amine nitrogen from each guanidine pendants coordinates to the copper(II) center in addition to the nitrogen atoms in the tacn macrocycle, resulting in a five-coordinate complex with intermediate square-pyramidal/trigonal bipyramidal geometry. The guanidines adopt an unusual coordination mode in that their amine nitrogen nearest to the tacn macrocycle binds to the copper(II) center, forming very stable five-membered chelate rings.
View Article and Find Full Text PDFThe tricyclic sesquiterpenol (+)-longifolol served as a lead structure for the design of inhibitors of the human UDP-glucuronosyltransferase (UGT) 2B7. Twenty-four homochiral and epimeric longifolol derivatives were synthesized and screened for their ability to inhibit the enzyme. The absolute configuration at the stereogenic center C1' was determined by X-ray crystallography and 2D NMR spectroscopy (gHSQC, gNOESY).
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