Charles W. Spangler

New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse

Purpose: The aim of this study was to show that novel photodynamic therapy (PDT) sensitizers can be activated by two-photon absorption in the near-IR region of the spectrum and to show, for the first time, that such activation can lead to tumor regressions at significant tissue depth. These experiments also evaluated effects of high-energy femtosecond pulsed laser irradiation on normal tissues and characterized the response of xenograft tumors to our PDT protocols. Experimental Design: Human small cell lung cancer (NCI-H69), non-small cell lung cancer (A549), and breast cancer (MDA-MB-231) xenografts were induced in SCID mice. Irradiation of sensitized tumors was undertaken through the bodies of tumor-bearing mice to give a treatment depth of 2 cm. Posttreatment tumor regressions and histopathology were carried out to determine the nature of the response to these new PDT agents. Microarray expression profiles were conducted to assess the similarity of responses to single and two-photon activated PDT. Results: Regressions of all tumor types tested were seen. Histopathology was consistent with known PDT effects, and no, or minimal, changes were noted in irradiated normal tissues. Cluster analysis of microarray expression profiling showed reproducible changes in transcripts associated with apoptosis, stress, oxygen transport, and gene regulation. Conclusions: These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was consistent with known responses to single-photon activated PDT. Experiments in larger animals are warranted to determine the maximal achievable depth of treatment.

Dendrimer molecules with record large two-photon absorption cross section

We report what is to our knowledge a record high value for an intrinsic two-photon absorption (TPA) cross section, sigma(2) = 11 x 10(-47)> cm>(4)> s photon(-1) molecule(-1), measured with femtosecond pulses in a new dendrimer molecule comprising 29 repeat units of 4, 4(?)-bis(diphenylamino)stilbene chromophore. We measure the dependence of TPA on excitation wavelength in three consecutive generations of the dendrimer and show that the maximum sigma(2) value increases faster than the total number of stilbene chromophores. This result indicates that it is possible to obtain even larger sigma(2) values in higher generations of this dendrimer family.

Enhancement of two-photon absorption in tetrapyrrolic compounds

We study the enhancement of two-photon absorption (TPA) in a series of porphyrins and tetraazaporphyrins by measuring the absolute TPA cross sections with 100-fs-duration pulses in two ranges of laser wavelengths, from 1100 to 1500 and from 700 to 800 nm. The cross section in the Q transition region is σ2∼1–10 GM (where 1 GM=10-50 cm4 s-1 photons-1), a value that is explained by partial lifting of the prohibition that is due to a parity selection rule. In the Soret transition region we find σ2 enhancement by ∼1 order of magnitude owing to the Q transition, which acts as a near-resonance intermediate state, and also owing to the presence of gerade energy levels, which we identify in this spectral region. In tetraazaporphyrins symmetrically substituted with strong electron acceptors, we find further enhancement (up to σ2∼1600 GM). As a possible application, we demonstrate for the first time to our knowledge the photosensitization of singlet-oxygen luminescence by TPA in porphyrin.

Vibronic structure in the optical absorption spectra of phenylene vinylene oligomers: a joint experimental and theoretical study

Abstract We present a joint experimental and theoretical investigation of the optical absorption spectra of phenylene vinylene oligomers. The vibronic structure, which is clearly observed in the experimental spectra, is well described by a simple model based on the Frank-Condon approximation but requires the use of at least two effective modes coupled to the electronic states. Using a fitting procedure, we deduce the displacement of the 1 B u excited state potential energy curve relative to that of the ground state and compare it to the results of recent Hartree-Fock semi-empirical calculations. Such information is of prime importance in the description of the frequency-dependent linear as well as nonlinear optical responses.

Efficient singlet oxygen generation upon two-photon excitation of new porphyrin with enhanced nonlinear absorption

We demonstrate efficient generation of singlet oxygen upon two-photon excitation with 150-fs 780-nm laser pulses of a new porphyrin photosensitizer molecule whose two-photon absorption cross section has been considerably enhanced by chemical design.

The crystal structure of trans,trans-1,3,5,7-octatetraene as a model for fully-ordered trans-polyacetylene

Abstract The crystal structure of trans,trans -1,3,5,7-octatetraene has been determined using x-ray diffraction techniques. This crystal structure, the first for an unsubstituted polyene, is used to predict the molecular and crystallographic structures of trans -polyacetylene. The structure of the octatetraene crystal is monoclinic, P2 1 /c, and has two centrosymmetric molecules in a unit cell with dimensions a = 10.228(8) A , b = 4.120(1) A , c = 8.313(3) A , and β = 96.53(4)°. The carbon skeleton is planar to within the experimental error and the carbon-carbon bond lengths starting from the chain end are 1.336(4), 1.451(3), 1.327(4), and 1.451(5) A. The average CCC angle is 125.0(3)°. From the intermolecular packing mode of octatetraene, the predicted structure of trans -polyacetylene is monoclinic, P2 1 /n, with a = 7.38 A , b = 4.12 A , c = 2.47 A ( chain axis ), β = 97.8° , and two chains per unit cell (2C 2 H 2 units). These axial lengths deviate at most by 1% from the average of three experimental determinations using x-ray diffraction and suggest that alternate proposed cells are less likely. Likewise, the predicted setting angle of the polymer chain (52.7° relative to the (010) of the present cell) is in good agreement with the results of crystal energy calculations (51.0°) and x-ray diffraction analyses (55°). Using the octatetraene data, the predicted single-bond length, double-bond length and CCC angle in trans -polyacetylene are 1.451(5) A, 1.327(4) A, and 125.3(4)°. These results are in reasonable agreement with bond lengths derived from nutation n.m.r. studies on trans -polyacetylene ( 1.44 ± 0.02 a and 1.36 ± 0.02 A ). The dimerization parameter ( μ 0 ) derived from the octatetraene results is 0.035(1) A, which can be compared with values previously estimated from the analysis of the limited available electron and x-ray diffraction intensities for poorly ordered trans -polyacetylene ( 0.012 ± 0.001 A and 0.03 A , respectively.

Preparation of Conjugated Aromatic Polyenals by Wittig Oxopropenylation

Abstract Heteroaromatic, or aromatic polyenals containing either electron-donating or withdrawing substituents can now be prepared easily in excellent yield by Wittig oxopropenylation with 1,3-dioxan-2-yl methyltributyl phosphorane

Reactions of low work function metals Na, Al, and Ca on α,ω‐diphenyltetradecaheptaene. Implications for metal/polymer interfaces

The interactions between different low work function metals aluminium,calcium and sodium, and α,ω‐diphenyltetradecaheptaene, a model molecule for certain conjugated polymers, have been investigated using both x‐ray photoelectron spectroscopy and ultraviolet photoelectron spectroscopy. The spectra are interpreted with the help of the results of quantum chemical calculations performed within the local spin density (LSD) approximation methodology. The metals are found to interact with the conjugated system in very different ways. Aluminium forms a covalent bond, which strongly modifies the π‐electronic structure of the conjugated molecule, while both the sodium and the calcium atoms act as doping agents, inducing new states in the otherwise forbidden bandgap. These new gap states can be viewed as a soliton–antisoliton pair for the Na/DP7 and a bipolaronic‐like defect for Ca/DP7.

New copolymers for applications as organic LEDs

During the past five years, (pi) -conjugated organic polymers, such as poly[p-phenylene vinylene] (PPV) and polythiophenes, have become attractive alternatives to semiconducting materials as light-emitting diodes. Various approaches to tuning emission wavelength have been proposed, such as controlling the conjugation length by employing polymer oligomers or via steric effects in the fully conjugated polymers, or by using substituent effects to fine-tune the band gap. In the present study, we demonstrate that these features can be designed into copolymeric structures in which (pi) -conjugated emitters of carefully controlled length alternate with various non-emitting flexible spacers which improve solubility and thus processibility. These copolymers display predictable emission characteristics which can also be fine-tuned by incorporation of electronic substituent effects.

Excited state energies and internal conversion in diphenylpolyenes: from diphenylbutadiene to diphenyltetradecaheptaene

Abstract Time-resolved and steady-state fluorescence investigations on a series of α,ω-diphenylpolyenes have been made. Dual S 1 /S 2 fluorescence was observed for polyenes with more than three double bonds in the polyene chain and the intensity and lifetime of the S 1 fluorescence decreased with increasing chain length. The 1B u energy was almost inversely proportional to the square root of the total molecular length. A similar dependence was found for the energy of the 1A g level, but the length without the phenyl rings was used. The logarithm of the S 1 →S 0 internal conversion rate in long-chain diphenylpolyenes exhibits a linear dependence on the S 1 energy. The rate in diphenylhexatriene is slightly higher than the value predicted from the linear dependence, while the internal conversion of diphenylbutadiene is much faster due to stronger S 1 –S 2 interaction.