Light Dosimetry for Intraperitoneal Photodynamic Therapy in a Murine Xenograft Model of Human Epithelial Ovarian Carcinoma

Few studies have been published to date measuring spatially resolved fluence rates in complex tissue geometries. Here the light distributions of three different intraperitoneal light delivery geometries in a murine ovarian cancer model were investigated to assess their influence on the tumorcidal efficacy of photodynamic therapy (PDT). In vivo fluence rate measurements in the peritoneal cavities of mice, with the light intensity being mapped in three transverse planes, were performed using fiber-optic detectors. Three different source fiber designs and placements were tested for their ability to provide uniform irradiation of the peritoneal cavity. The biological response to a PDT protocol comprising three separate treatments administered at 72 h intervals, each consisting of a 0.25 mg kg intraperitoneal injection of benzopor-phyrin derivative-mono acid ring A followed 90 min later by delivery of 15 J of 690 nm light, was measured. The tissue response was evaluated by measuring the number of remaining visible lesions and the total residual tumor mass. Fluence rate measurements showed large variations in the fluence rate distribution for similar intended treatments. The most uniform and reproducible illumination was achieved using two 18 mm long cylindrical emitting optical fibers. The biological response was comparable to that produced when a flat-cleaved end optical fiber is used to illuminate the four quadrants of the abdomen sequentially. While a good reproducibility in tumor induction in this animal model exists, no correlation was found between the fluence rate distribution measured in one group of animals and the biological response in a separate group of similarly treated animals. Due to the large intra-animal variability in fluence rate distribution, representative fluence rate mapping in complex tissue geometries is of limited value when applied to an individual PDT treatment. Thus, surveillance of the fluence rate during individual treatments will be required for acceptable PDT dosimetry. To improve the versatility of this particular animal model for PDT research, a large number of extended sources are required to increase uniformity of the illumination in order to reduce unwanted cytotoxic side effects resulting from foci of high fluence rates. In this way, subsequent increase of the total energy delivered to the tumor may be possible.     

Intermolecular diels-alder reactions of n-acyl-n-alkyl(aryl)-1-amino-1,3-dienes

Intermolecular Diels-Alder additions of the readily available dienamides $\text{3}$ to various dienophiles proceeded in a regio- and stereoselective manner, allowing the preparation of complex anilides ($\text{5}$), cyclohexenyl amides ($\text{6}$, $\text{8}$) and bridged heterocycles ($\text{13}$).     

Three distinct distances in the plane

For n6 all sets of n points in the plane with three distinct distances are determined.Dedicated to Professor Dr. Laszlo Fejes Töth on the occasion of his eightieth birthday     

Composition and properties of freeze-dried products of nicotinic acid withβ-cyclodextrin and heptakis (2,6-0-dimethyl)-β-cyclodextrin

The purpose of the study was to examine the formation of inclusion compounds in the freeze-dried products obtained from aqueous solutions of nicotinic acid and -cyclodextrin (-CD), or heptakis (2,6-0-dimethyl)--cyclodextrin (DIMEB). The molar ratios used were 1:1 and 2:1. In addition two freezing temperatures (–40 and –196°C) and different secondary drying temperatures (+50 and +80°C) were used. Freeze-dried products with -CD obtained after low temperature freezing are of the same crystallographic structure as seen in a pure inclusion compound prepared by coprecipitation. Amorphous products were formed after fast freezing. The molar ratios of included nicotinic acid in the freeze-dried products vary — dependent on the preparation conditions — between 0.75:1 and 1:1. A factorial design proves that the included drug amount can be increased by enhancement of the amount of nicotinic acid used, by faster freezing, and by the combination of these two factors. The proof of inclusion formation was given by a combination of X-ray diffractography, differential scanning calorimetry, thermogravimetry and thermofractography.The freeze-dried preparations obtained with DIMEB were amorphous mixtures of the two components. No proof for inclusion of the nicotinic acid in the cyclodextrin cavity could be given. Higher (–40°C) or lower (–196°C) freezing temperatures and the running of the secondary drying process could not influence these results. The very low stability constant of the complex and steric reasons are responsible for this behavior.     

High-Resolution,Higher-Order UV/VIS Derivative Spectrophotometry

Derivative spectrophotometry has gained increasing importance in the past two years and is currently experiencing vigorous development. Following and introduction the present article provides a review of this extremely effective method. In particular, the advantages of higher-order derivative spectrophotometry (HODS method, n > 2) are discussed on the basis of practical examples from a wide range of analytical fields. The results are achieved with the aid of a newly developed analog computer unit, whereby for the first time readily reproducible, low-noise, on-line spectra can be obtained up to the 7th order and even, in favorable cases, up to the 9th order. In practice it has proved valuable to work with spectra of the 3rd to 5th order; but even higher derivations could be profitable for the separation of strongly superposed signals or for “fingerprinting”.     

Ab initio studies of structural features not easily amenable to experiment. 17. The molecular structures of some strained cyclic hydrocarbons and estimates of their strain energies

The molecular structures of tricyclohexane, norbornane, quadricyclane, and cubane were completely refined by standard ab initio force relaxation on the 4-21G level. The results can be used as a basis to interpret some contradictory experimental reports found in the literature and to establish some hitherto unobserved structural trends involving the C? C and C? H bond distances of the cases studied. Group Delta;E values for C? (H)₃(C), C? (H)₂(C)₂, and C? (H)(C)₃ (Benson's notation) derived from the total energies of the completely relaxed 4-21G geometries of a number of unstrained hydrocarbons are also listed. The values are used to estimate the strain energies of the systems studied and of the optimized 4-21G geometries of cyclopropane, cyclobutane, cyclohexane, and bicyclo (2.1.0)pentane. Cooperative effects in the strain energies are discussed.     

‘Face-to-Face’-Benzo-anellierte homologe Hypostrophene. Synthesen,Röntgenstrukturanalysen und PE-Spektren

‘Face-to-Face’ Benzo-anellated Homologous Hypostrophenes. Syntheses, X-Ray-Structure Analyses and PE Spectra ‘Face-to-face’ Benzo-anellated homologous hypostrophenes (series M ), of interest as substrates for [6 + 6]-photocycloaddition reactions, have been synthesized. From X-ray structural analyses of 13b and 13c shortest C? C distances of 2.80(2.76)/2.71 Å and interorbital angles (ω) of 129° (128°)/130° between the benzene rings have been determined. The PE spectra are discussed in the context of transannular π,π interactions.     

Infrared absorption by collisional CH4+X pairs, with X=He, H2, or N2

Existing measurements of the collision-induced rototranslational absorption spectra of gaseous mixtures of methane with helium, hydrogen, or nitrogen are compared to theoretical calculations, based on refined multipole-induced and dispersion force-induced dipole moments of the interacting molecular pairs CH4-He, CH4-H2, and CH4-N2. In each case the measured absorption exceeds the calculations substantially at most frequencies. We present the excess absorption spectra, that is the difference of the measured and the calculated profiles, of these supramolecular CH4-X systems at various gas temperatures. The excess absorption spectra of CH4-X pairs differ significantly for each choice of the collision partner X, but show common features (spectral intensities and shape) at frequencies from roughly 200 to 500 cm(-1). These excess spectra seem to defy modeling in terms of ad hoc exchange force-induced dipole components attempted earlier. We suggest that besides the dipole components induced by polarization in the electric molecular multipole fields and their gradients, and by exchange and dispersion forces, other dipole induction mechanisms exist in CH4-X complexes that presumably are related to collisional distortion of the CH4 molecular frame.     

New aspects in the reaction of azomethines with cyclic CH-acidic compounds

Summary Treatment of substituted benzylidene anilines1 a – df with cyclic CH-acidic compounds2a–m in ethanol at room temperature yields in additon/elimination reactions the corresponding arylidene derivatives4 and the 2:1 adducts5. The addition products3, which are formed as intermediates, could not be isolated in any case. The donor/acceptor effect of the substituents on the benzylidene moiety influences to a significant extent the reactivity towards the azomethine carbon.

---

Neue Aspekte der Reaktion von Azomethinen mit cyclischen CH-aciden Verbindungen

Zusammenfassung Bei der Umsetzung der substituierten Benzylidenaniline1 a – f mit den cyclischen CH-aciden Verbindungen2 a – m in Ethanol bei Raumtemperatur erhält man in Additions/Eliminierungsreaktionen die Arylidenderivate4 und die 2:1-Addukte5. Die als Intermediat gebildeten Additionsprodukte3 konnten in keinem Fall isoliert werden. Die Donor-bzw. Acceptorwirkung der Substituenten am Benzylidenrest beeinflußt maßgebend die Reaktivität am Azomethinkohlenstoff.