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Boron neutron capture therapy (BNCT) is a binary cancer treatment that involves the irradiation of 10B-containing tumors with low-energy neutrons (thermal or epithermal). The alpha particles and recoiling Li nuclei that are produced in the 10B-capture nuclear reaction are high-linear-energy transfer particles that destroy boron-loaded tumor cells; therefore, BNCT has the potential to be a localized therapeutic modality. Two boron-delivery agents have been used in clinical trials of BNCT in patients with malignant brain tumors, cutaneous melanoma, or recurrent tumors of the head and neck region, demonstrating the potential of BNCT in the treatment of difficult cancers. A variety of potentially highly effective boron-delivery agents have been synthesized in the past four decades and tested in cells and animal models. These include boron-containing nucleosides, peptides, proteins, polyamines, porphyrins, liposomes, monoclonal antibodies, and nanoparticles of various types. The most promising agents are multi-functional boronated molecules and nanoparticles functionalized with tumor cell-targeting moieties that increase their tumor selectivity and contain a radiolabel or fluorophore to allow quantification of 10B-biodistribution and treatment planning. This review discusses multi-functional boron agents reported in the last decade, but their full potential can only be ascertained after their evaluation in BNCT clinical trials. 

Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 (15) are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, esophageal, and brain cancers. After the initial misidentification of the structure of this chlorin-e6 aspartic acid conjugate as (13), NMR and other synthetic procedures described herein arrived at the correct structure (15), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e6 chemistry (including the intramolecular formation of an anhydride (24)) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 131 (formic), 152 (acetic), and 173 (propionic) of chlorin e6 (14). Cellular investigations of several amino acid conjugates of chlorin-e6 revealed that the 131-aspartylchlorin-e6 derivative is more phototoxic than its 152- and 173-regioisomers, in part due to its nearly linear molecular conformation. 

Some of the most persistent challenges facing society and the environment arise from an intricate coupling of natural and human systems (CNHS). These challenges resist traditional expert-driven problem-solving approaches and require a careful synthesis of both “explanation” and “understanding” to achieve equity and sustainability. Whereas, explanations tend to be the domain of scientific experts who seek generalizable solutions through theory building, modeling, and testing, understandings represent the wisdom of practitioners that enables real-world problem solving to proceed by accounting for contextual values, capacities, and constraints. Using a case study from Bangladesh as an illustrative case of CNHS, we take an explanatory approach in using the extended case study method to show why and how an expert-led response to remediation of arsenic-contaminated wells led to unintended outcomes, which could have been accounted for if a complexity science informed framework of the problem was in place. The complexity frame keeps one alert to emergent patterns that otherwise remain unanticipated, and thereby, form the basis of adaptive actions. For a path forward in addressing complex CNHS problems, we introduce a novel problem-solving approach that combines pragmatic explanations and interpretive understandings with attention to emergent patterns. We argue that this problem-solving approach – which we term principled pragmatism – can effectively synthesize and apply scientific knowledge and local practical knowledge to develop and implement adaptive, actionable, and sustainable interventions.

 

A 1,3,5,7-tetramethyl-8-(2,4,6-triphenylphenyl)-BODIPY and its 2,6-dichloro derivative were synthesized and their spectroscopic properties compared experimentally and computationally with those of the corresponding 8-phenyl and 8-mesityl derivatives. The new 2,6-dichloro-1,3,5,7-tetramethyl-8-(2,4,6-triphenylphenyl)-BODIPY shows the highest fluorescence quantum yields in dichloromethane and toluene. 

The synthesis and reactivity of 3,8‐dibromo‐dodecafluoro‐benzo‐fused BOPHY2are reported, via S_NAr with O‐, N‐ S‐ and C‐nucleophiles, and in Pd(0)‐catalyzed cross‐coupling reactions (Suzuki and Stille). The resulting perfluoro‐BOPHY derivatives were investigated for their reactivity in the presence of various nucleophiles. BOPHY3displays reversible color change and fluorescence quenching in the presence of bases (Et₃N, DBU), whereas BOPHY7reacts preferentially at the α‐pyrrolic positions, and BOPHY8undergoes regioselective fluorine substitution in the presence of thiols. The structural and electronic features of the fluorinated BOPHYs were studied by TD‐DFT computations. In addition, their spectroscopic and cellular properties were investigated; BOPHY10shows the most red‐shifted absorption/emission (λ_max659/699 nm) and7the highest fluorescence (Φ_f=0.95), while all compounds studied showed low cytotoxicity toward human HEp2 cells and were efficiently internalized.