Biomedical subjects
Publications and source records attributed to Joseph W Perry.
Extended bis(donor)-substituted squaraine chromophores exhibit very high two-photon cross-sections (as high as 33 000 GM) in the near-IR; these can be attributed to the combination of large transition dipoles with small detuning energies. The modulus of the third-order nonlinear optical susceptibility at 1.3 mum has been found to be 7.0 x 10-11 esu for one of these chromophores.
Organic materials with large third-order nonlinearities in the near-infrared spectral regime are critical in the development of photonic devices to be utilized in all-optical signal processing. We have developed polymethine materials, specifically bisdioxaborine-terminated polymethine dyes, which possess large ultrafast third-order nonlinearities and low nonlinear loss all in the near-infrared spectral regime. An extended bisdioxaborine polymethine anion exhibited the largest value of gamma (third-order microscopic nonlinearity) at 1.3 mum (|gamma| = 5.7 x 10-32 esu) and showed no characteristics of symmetry breaking, unlike other polymethines of similar lengths. A neat film of this molecule maintained relatively low linear loss in the near-infrared and showed a large third-order macroscopic nonlinearity at 1.3 mum (|chi(3)| = 3.6 x 10-10 esu), with a temporal response of less than 8 ps. Furthermore, the real part of chi(3) was nearly an order-of-magnitude larger than the imaginary component. Consequently, this material exhibited good figures of merit for all-optical signal processing throughout the entire telecommunications band.
A multifunctional ligand-coated nanoparticle system containing approximately 2000 highly two-photon absorptive chromophores has been investigated by means of steady-state and femtosecond time-resolved spectroscopy. This system with a high local concentration of chromophores showed remarkably low self-quenching and a high fluorescence quantum yield, which is important for a variety of two-photon sensing and imaging applications. We have observed evidence for ultrafast energy migration in these chromophore shell-metal nanoparticle systems. Time-resolved experiments also showed non-zero residual anisotropy after the initial fast decay, which can be interpreted as due to the formation of the specific domains on the metal surfaces. This investigation opens new avenues toward the development of multi-chromophoric efficient TPA fluorescence sensing/imaging systems with large numbers of chromophores per one metal particle nanoparticle.
Melanocortin hormones and neurotransmitters regulate a vast array of physiologic processes by interacting with five G-protein-coupled melanocortin receptor types. In the present study, we have systematically studied the regulation of individual human melanocortin receptor wild subtypes using a synthetic rhodamine-labeled human melanotropin agonist and antagonist, arrestins fused to green fluorescent protein in conjunction with two-photon fluorescence laser scanning microscopy and confocal microscopy. Stimulation of the melanocortin receptors by its cognate agonist triggered rapid arrestin recruitment and receptor internalization for all four human melanocortin receptors examined. Antagonists-bound melanocortin receptors, on the other hand, did not recruit beta-arrestins, and remained in the cell membrane even after long-term (30 min) treatment. Agonist-mediated internalization of all melanocortin receptor subtypes was sensitive to inhibitors of clathrin-dependent endocytosis, but not to caveolae inhibitors. In summary, agonist-mediated internalization of all subtypes of melanocortin receptors are dependent upon beta-arrestin-mediated clathrin-coated pits, whereas, beta-arrestin-2 conjugated green fluorescence protein (beta-arrestin-2-GFP) recruitment is not dependent on protein kinase A activation. Real time two-photon fluorescence laser scanning microscopy is a most powerful tool to study the dynamic processes in living cells and tissues, without inflicting significant and often lethal damage to the specimen.
Three quadrupolar oligophenylenevinylenes with five rings in the conjugated backbone, terminal donor groups, and various acceptors and/or donors along the backbone were synthesized and their two-photon spectroscopic properties investigated. These chromophores exhibit large two-photon absorption cross sections over a wide wavelength range and two distinct peaks, the strongest of which (deltamax > 3600 GM) is observed at 960-970 nm, a wavelength close to twice the value of the linear absorption maximum (2lambda(1)max). The findings on these chromophores are compared with those for analogous molecules with shorter conjugation length, for which the main two-photon band is at significantly shorter wavelength than 2lambda(1)max.
A series of alpha,omega-bis donor substituted oligophenylenevinylene dimers held together by the [2.2]paracyclophane core were synthesized to probe how the number of repeat units and through-space delocalization influence two-photon absorption cross sections. Specifically, the paracyclophane molecules are tetra(4,7,12,15)-(4'-dihexylaminostyryl)[2.2]paracyclophane (3R(D)), tetra(4,7,12,15)-(4' '-(4'-dihexylaminostyryl)styryl)[2.2]paracyclophane (5R(D)), and tetra(4,7,12,15)-(4' "-(4' '-(4'-dihexylaminostyryl)styryl)styryl)[2.2]paracyclophane (7R(D)). The compounds bis(1,4)-(4'-dihexylaminostyryl)benzene (3R) and bis(1,4)-(4' '-(4'-dihexylaminostyryl)styryl)benzene (5R) were also synthesized to reveal the properties of the "monomeric" counterparts. The two-photon absorption cross sections were determined by the two-photon induced fluorescence method using both femtosecond and nanosecond pulsed lasers as excitation sources. While there is a red shift in the linear absorption spectra when going from the "monomer" chromophore to the paracyclophane "dimer" (i.e., 3R --> 3R(D), 5R --> 5R(D)), there is no shift in the two-photon absorption maxima. A theoretical treatment of these trends and the dependence of transition dipole moments on molecular structure rely on calculations that interfaced time-dependent density functional theory (TDDFT) techniques with the collective electronic oscillator (CEO) program. These theoretical and experimental results indicate that intermolecular interactions can strongly affect B(u) states but weakly perturb A(g) states, due to the small dipole-dipole coupling between A(g) states on the chromophores in the dimer.
Chromophores based on a donor-acceptor-donor structure possessing a large two-photon absorption cross section and one or two mono-aza-15-crown-5 ether moieties, which can bind metal cations, have been synthesized. The influence of Mg(2+) binding on their one- and two-photon spectroscopic properties has been investigated. Upon binding, the two-photon action cross sections at 810 nm decrease by a factor of up to 50 at high Mg(2+) concentrations and this results in a large contrast in the two-photon excited fluorescence signal between the bound and unbound forms, for excitation in the range of 730 to 860 nm. Experimental and computational results indicate that there is a significant reduction of the electron donating strength of the aza-crown nitrogen atom(s) upon metal ion binding and that this leads to a blue shift in the position as well as a reduction in the strength of the lowest-energy two-photon absorption band. The molecules reported here can serve as models for the design of improved two-photon excitable metal-ion sensing fluorophores.
Quantum-chemical calculations of the two-photon absorption (TPA) cross-sections are used to determine the characteristics of the electronic excited states responsible for the observed peaks in the TPA spectra of two bis-dioxaborine-substituted biphenyl derivatives. We find two distinct TPA-active states with very different TPA cross-sections: the difference is explained on the basis of electron correlation. These effects, on the one hand, lead to TPA cross-sections of up to 500 x 10(-50) cm4 s photon(-1) for the state favored by correlation; on the other hand, they limit the overall cross-sections achievable in this class of materials.
Receptor-based signaling mechanisms are the primary source of cellular regulation. The superfamily of G protein-coupled receptors (GPCR) is the largest and most ubiquitous of the receptor-mediated processes. Desensitization of G-protein-coupled receptors is a fundamental mechanism regulating the cellular response to agonists. We have recently studied the agonist and antagonist of the human melanocortin receptors (hMC1, hMC3, hMC4, and hMC5 receptors), the human delta opioid receptor, and the human gluacagon receptor with the help of synthetic fluorescent labeled ligands and fluorescent protein-labeled beta-arrestin-receptors that shed new insight on cellular signaling and rapid screening of drugs in real time. It was demonstrated that stimulation of these receptors by the cognate agonist triggers the rapid internalization of ligand-receptor complexes, while the interaction of the receptor with antagonists does not follow this pathway. Furthermore, receptor internalization is dependent upon beta-arrestin, which has been shown to be responsible for the rapid desensitization of cAMP-signaling processes.
Silver nanoparticles coated with a self-assembled layer of approximately 2500 chromophoric alkylthiol ligands, that exhibit a huge per particle two-photon absorption cross section (2.7 x 10-45 cm4 s photon-1) and a high fluorescence quantum yield (0.33), are reported. Polyfunctionalized variants of these nanoparticles have been produced that show reasonable solubility in water/ethanol mixtures. By virtue of the large number of tethered chromophores, these particles act as strongly two-photon absorbing nanobeacons and may have applications in fluorescence imaging and sensing.
A two-photon-activatable photoacid generator, based on a bis[(diarylamino) styryl]benzene core with covalently attached sulfonium moieties, has been synthesized. The photoacid generator has both a large two-photon absorption cross section (delta = 690 x 10(-50) centimeter(4) second per photon) and a high quantum yield for the photochemical generation of acid (phiH+ = 0.5). Under near-infrared laser irradiation, the molecule produces acid after two-photon excitation and initiates the polymerization of epoxides at an incident intensity that is one to two orders of magnitude lower than that needed for conventional ultraviolet-sensitive initiators. This photoacid generator was used in conjunction with a positive-tone chemically amplified resist for the fabrication of a three-dimensional (3D) microchannel structure.
New triarylamine dialkylsulfonium salts that are photosensitive in the near-ultraviolet have been prepared. The quantum yields of photoacid generation were found to be approximately 0.5 and are independent of the counterion. On the other hand, the efficiencies of the sulfonium salts toward the photopolymerization of cyclohexene oxide depend on the counterion and the sulfonium substituents. Photopolymerization kinetic studies demonstrate that these triphenylamine sulfonium salts are highly efficient cationic photoinitiators.