Lanthanide Luminescent Displacement Assays: The Sensing of Phosphate Anions Using Eu(III)−Cyclen-Conjugated Gold Nanoparticles in Aqueous Solution

Lanthanide Luminescent Displacement Assays: The Sensing of Phosphate Anions Using Eu(III)−Cyclen-Conjugated Gold Nanoparticles in Aqueous Solutio

Hook, Line, and Sinker! Spectroscopic Studies of Bi-Modular Mono- and Bis-1,8-naphthalimide-Ru(bpy)₃‑conjugates as DNA “Light Switches”

Bi-chromophoric ruthenium polypyridyl complexes comprising one or two nitro-1,8-naphthalimide groups are shown to be effective DNA binders with off–on light switching properties. The binding to DNA was investigated using a combination of studies such as UV–visible absorption and emission titrations, thermal denaturation, and circular dichroism spectroscopy. The DNA affinity was shown to be sensitive to both the linker length and the number of naphthalimides (one vs two) contained in these systems and binding constants ranging from 106 to 107 M–1 for salmon testes DNA. The strong DNA binding is attributed to the combination of naphthalimide intercalation and the electrostatic interaction of the ruthenium complex. Large emission enhancements from the metal to ligand charge transfer (MLCT) emission arising from the metal complex were observed upon DNA binding, which was attributed to the interruption of intramolecular electron transfer quenching processes. Moving the nitro substitution from the 4-position to the 3-position is found to result in modification of the DNA binding and the resulting optical properties. The off–on light switch phenomena reported demonstrate the potential of these complexes to act as DNA probes

Mixed f−d Coordination Complexes as Dual Visible- and Near-Infrared-Emitting Probes for Targeting DNA

A new family of mixed-lanthanide (YbIII and NdIII) transition-metal (f−d) cyclen-RuII(phen)3 (phen = 1,10-phenanthroline) complexes were synthesized as dual visible- and near-infrared (NIR)-emitting DNA probes/sensors. Significant changes were seen in both the RuII visible and the YbIII-centered NIR emission, which was switched off upon binding to DNA at pH 7.4. In contrast, no changes were seen in the NdIII emission of the analogue f−d conjugate

Asymmetrical Diaromatic Guanidinium/2-Aminoimidazolinium Derivatives: Synthesis and DNA Affinity

In this paper we report the synthesis of three families of new amidine-based aromatic derivatives as potential DNA minor groove binding agents for the treatment of cancer. The preparation of monoguanidine, mono-2-aminoimidazoline, and asymmetric diphenylguanidine/2-aminoimidazoline derivatives (compounds 1a−c to 8a−c) is presented. The affinity of these substrates and of a family of mono- and bis-isoureas (previously prepared in Rozas’ laboratory) for DNA was evaluated by means of DNA thermal denaturation measurements. In particular, compounds 2c, 5c, 6c, 7c, and 8c were found to bind strongly both to natural DNA and to adenine−thymine oligonucleotides, showing a preference for the adenine−thymine base pair sequences

Cellular Uptake Mediated Off/On Responsive Near-Infrared Fluorescent Nanoparticles

Fluorescence imaging, utilizing molecular fluorophores, often acts as a central tool for the investigation of fundamental biological processes and offers huge future potential for human imaging coupled to therapeutic procedures. An often encountered limitation with fluorescence imaging is the difficulty in discriminating nonspecific background fluorophore emission from a fluorophore localized at a specific region of interest. This limits imaging to individual time points at which background fluorescence has been minimized. It would be of significant advantage if the fluorescence output could be modulated from off to on in response to specific biological events as this would permit imaging of such events in real time without background interference. Here we report our approach to achieve this for the most fundamental of cellular processes, i.e. endocytosis. We describe a new near-infrared off to on fluorescence switchable nanoparticle construct that is capable of switching its fluorescence on following cellular uptake but remains switched off in extracellular environments. This permits continuous real-time imaging of the uptake process as extracellular particles are nonfluorescent. The principles behind the fluorescence off/on switch can be understood by encapsulation of particles in cellular organelles which effect a microenvironmental change establishing a fluorescence signal

Ordered DNA Wrapping Switches on Luminescence in Single-Walled Nanotube Dispersions

An extensive study of the time dependence of DNA wrapping in single-walled nanotube (SWNT) dispersions has been carried out, revealing a number of unusual phenomena. SWNTs were dispersed in water with salmon testes DNA and monitored over a three-month period. Between 20 and 50 days after the sample was first prepared, the SWNT photoluminescence (PL) intensity was observed to increase by a factor of 50. This increase was accompanied by a considerable sharpening of the van Hove absorption peaks. High-resolution transmission electron microscopy (HRTEM) images showed the progressive formation of a coating of DNA on the walls of the nanotubes over the three-month period. HRTEM and circular dichroism spectroscopy studies showed that the improvement in both the NIR PL intensity and the van Hove absorption peaks coincided with the completion of a monolayer coating of DNA on the SWNT walls. HRTEM images clearly showed the DNA wrapping helically around the SWNTs in a surprisingly ordered fashion. We suggest that the initial quenching of NIR photoluminescence and broadening of absorption peaks is related to the presence of protonated surface oxides on the nanotubes. The presence of an ordered DNA coating on the nanotube walls mediates both deprotonation and removal of the surface oxides. An extensive DNA coating is required to substantially restore the photoluminescence, and thus, the luminescence switch-on and subsequent saturation indicate the completion of the DNA-wrapping process. The temperature dependence of the PL switch-on, and thus of the wrapping process, was investigated by measuring as functions of temperature both the time before PL switch-on and the time required for the PL intensity to saturate. This allowed the calculation of the activation energies for both the process preceding PL switch-on and the process limiting the rise of PL intensity, which were found to be 31 and 41 kJ mol−1, respectively. The associated entropies of activation were −263 and −225 J mol−1 K−1, respectively. These negative activation entropies suggest that the rate-limiting step is characterized by a change in the system from a less-ordered to a more-ordered state, consistent with the formation of an ordered DNA coating

Cellular Uptake Mediated Off/On Responsive Near-Infrared Fluorescent Nanoparticles

Fluorescence imaging, utilizing molecular fluorophores, often acts as a central tool for the investigation of fundamental biological processes and offers huge future potential for human imaging coupled to therapeutic procedures. An often encountered limitation with fluorescence imaging is the difficulty in discriminating nonspecific background fluorophore emission from a fluorophore localized at a specific region of interest. This limits imaging to individual time points at which background fluorescence has been minimized. It would be of significant advantage if the fluorescence output could be modulated from off to on in response to specific biological events as this would permit imaging of such events in real time without background interference. Here we report our approach to achieve this for the most fundamental of cellular processes, i.e. endocytosis. We describe a new near-infrared off to on fluorescence switchable nanoparticle construct that is capable of switching its fluorescence on following cellular uptake but remains switched off in extracellular environments. This permits continuous real-time imaging of the uptake process as extracellular particles are nonfluorescent. The principles behind the fluorescence off/on switch can be understood by encapsulation of particles in cellular organelles which effect a microenvironmental change establishing a fluorescence signal

Cellular Uptake Mediated Off/On Responsive Near-Infrared Fluorescent Nanoparticles

Fluorescence imaging, utilizing molecular fluorophores, often acts as a central tool for the investigation of fundamental biological processes and offers huge future potential for human imaging coupled to therapeutic procedures. An often encountered limitation with fluorescence imaging is the difficulty in discriminating nonspecific background fluorophore emission from a fluorophore localized at a specific region of interest. This limits imaging to individual time points at which background fluorescence has been minimized. It would be of significant advantage if the fluorescence output could be modulated from off to on in response to specific biological events as this would permit imaging of such events in real time without background interference. Here we report our approach to achieve this for the most fundamental of cellular processes, i.e. endocytosis. We describe a new near-infrared off to on fluorescence switchable nanoparticle construct that is capable of switching its fluorescence on following cellular uptake but remains switched off in extracellular environments. This permits continuous real-time imaging of the uptake process as extracellular particles are nonfluorescent. The principles behind the fluorescence off/on switch can be understood by encapsulation of particles in cellular organelles which effect a microenvironmental change establishing a fluorescence signal

Tracking DNA Excited States by Picosecond-Time-Resolved Infrared Spectroscopy: Signature Band for a Charge-Transfer Excited State in Stacked Adenine–Thymine Systems

UV photoexcitation of an adenine–thymine heterodimer (ApT) in D₂O yields a complex transient infrared signature in the 1500–1600 cm^–1 spectral region. The spectral dynamics fit well to a biexponential decay assignable to two transient species. The first, a short-lived species with a lifetime of ca. 5 ps, originates from the vibrationally hot electronic ground state of the unstacked form of the dinucleotide. The second species is longer-lived (ca. 75 ps), and its yield correlates to the amount of stacked dinucleotide present in solution. We assign the longer-lived component to a charge-transfer (A^•+pT^•–) state by comparison with calculated spectra for the adenine radical cation and thymine radical anion. Significantly, the CT feature is also identified in UV-excited [poly­(dA-dT)]₂. This experimental observation gives a powerful insight into how base–base interactions lead to extended-lifetime electronic excited states of the nucleic acid bases and how a dimeric structure controls the relaxation pathway