Formulation of benzoporphyrin derivatives in Pluronics

This study investigates the potential of Pluronics for the formulation of tetrapyrrole-based photosensitizers, with a particular focus on B-ring benzoporphyrin derivatives. The B-ring derivatives have a high tendency to aggregate in aqueous solutions, and this poses a significant formulation problem. Pluronics are ABA-type triblock copolymers composed of a central hydrophobic polypropylene oxide section with two hydrophilic polyethylene oxide sections of equal length at either end. Out of a range of different commercially available block copolymers studied, it was found that the longer the hydrophobic block, the better the stabilization of tetrapyrrolic drugs in monomeric form in aqueous suspensions. Of these the best performance was observed in the micelle-forming Pluronic P123. Micelle size determination by laser light scattering confirmed that particle size in stable Pluronic formulations was around 20 nm. Pluronics such as L122 formed emulsions spontaneously without the need for emulsion stabilizers; emulsions were highly stable at ambient temperatures over several days and also highly effective as potential drug delivery agents.     

Magnetic Resonance Imaging Evaluation of Photodynamic Therapy-Induced Hemorrhagic Necrosis in the Murine M1 Tumor Model

Abstract— Proton magnetic resonance imaging (MRI) and histological methods were used to evaluate photodynamic therapy (PDT)-induced hemorrhagic necrosis in the murine Ml tumor within 72 h of treatment of male DBA/2 mice. The effects of three photosensitizing drugs were investigated: Photofrin (n = 4), Zn (II) phthalocyanine (n = 7) and benzoporphyrin derivative monoacid ring A (n = 11). As noted in previous studies of PDT using MRI, MRI makes possible serial, noninvasive, in vivo observation of tissue response to PDT. Our serial study of MRI and histological data confirms that tumors responded in the same way to PDT treatment using the three photosensitizing drugs: vascular damage followed by hemorrhagic necrosis. Most importantly and unlike previous MRI studies of PDT, we used a very high field magnet that enhanced the effect of magnetic susceptibility on image signal when blood is processed by the body after PDT-induced hemorrhagic necrosis. This last finding demonstrates the utility of high field magnets and the importance of localized, serial experiments in future magnetic resonance studies of PDT.     

Skeletons and Central Sets

Let be an open proper subset of Rⁿ. Its skeleton is the setof points with more than one nearest neighbour in the complementof its central set is the set of centres in maximal open ballsincluded in . Intuitively, if we think of as a land mass inwhich height is proportional to distance from the sea, its skeletonand central set can be thought of as corresponding to ridgesin the mountains of . In this note I discuss the metric andtopological properties of such sets. I show that any skeletonin Rⁿ is F, and has dimension at most n – 1, by any ofthe usual measures of dimension; that if is bounded and connected,its skeleton and central set are connected; and that separatesRⁿ iff its skeleton does iff its central set does. Any centralset in Rⁿ is a G set of topological dimension at most n –1. In the plane, I show that both skeletons and central setsare locally path-connected, and indeed include many paths offinite length. For any , its central set includes its skeleton;I give examples to show that the central set can be significantlylarger than the skeleton. 1991 Mathematics Subject Classification:54F99.     

Interaction of Derivatized Capped Iron(II) Porphyrin Complexes with CO and O(2)

A series of porphyrins strapped and capped by benzene and amidobenzene rings have been prepared. O(2) and CO bindings to their iron(II) complexes have been examined, and the role of hydrogen-bonding in stabilizing O(2) binding has been measured. Each comparison between the benzene ring (no H-bonding) and the amidobenzene ring analogues showed a free energy gain of approximately 1 kcal/mol (at -45 degrees C) for the amidobenzene derivatives. An X-ray structure analysis was carried out for the ferric (Cl(-)) complex of the benzene-capped porphyrin strapped by two butyl side chains. The crystals were monoclinic, with a = 10.557(3) ?, b = 31.290(5) ?, c = 11.221(3) ?, beta = 104.62(2) degrees, Z = 4, and space group P2(1)/n. The structure was solved by the Patterson method and was refined by full-matrix least-squares procedures to R = 0.040 (R(w) = 0.041) for 3844 reflections with I >/= 3sigma(F(2)).     

Synthesis,crystal structures,and redox potentials of 2,3,12,13-tetrasubstituted 5,10,15,20-tetraphenylporphyrin zinc(II) complexes

Zinc(II) complexes of antipodal beta-tetrasubstituted meso-tetraphenylporphyrin with trifluoromethyl (Zn(TPP(CF(3))(4)) (1a)), bromine (Zn(TPPBr(4)) (2a)), and methyl groups (Zn(TPP(CH(3))(4)) (3a)) were synthesized in order to examine the steric and the electronic effects of trifluoromethyl groups on the macrocycle. The analysis of X-ray crystal structures of the five-coordinate complexes Zn(TPP(CF(3))(4))(EtOH)(3) (1b), Zn(TPPBr(4))(MeOH)(DMF) (2b), and Zn(TPP(CH(3))(4))(THF)(1.6)(CHCl(3))(0.4) (3b) revealed distorted macrocyclic cores where significant differences in the Zn-N distance between the beta-substituted and the non-beta-substituted side were observed. The difference was significant in 1b due to the strong steric interactions among the peripheral substituents and the electronic effects of trifluoromethyl groups. The macrocycles of 1b-3b are saddle-distorted and slightly ruffled due to the five-coordination of zinc(II) and the peripheral substitution. Distortion of the macrocycles of 2b and 3b were modest. On the other hand, distortion in 1b was severe due to the peripheral strain. Cyclic voltammetric measurements of the four-coordinate complexes Zn(TPP) and 1a-3a were performed and their redox potentials were analyzed together with previously reported potentials of Zn(TPP(CN)(4)). The oxidation potential of 1a did not gain as much as expected from the electron-withdrawing effect of the four trifluoromethyl groups. The HOMO-LUMO gap of 1a was very small (1.5 V) and cannot just be explained by macrocyclic distortion. The magnitude of this gap is very similar to that of Zn(TPP(CN)(4)). Compound 2a also exhibited a modest gap contraction. Compound 3a was easier to oxidize and harder to reduce than Zn(TPP), even though the HOMO-LUMO gap of 3a was similar to that of Zn(TPP).