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PET-Trackable Carborane-Conjugated Star-Shaped Poly(2-Oxazoline) Scaffold with High Boron Payload and Improved
Yuquan Chi1, Diana Barakhtii1, Alessia Centanni1
1Department of Chemistry, University of Helsinki, FI-00014Helsinki, Finland.
Abstract:
Boron neutron capture therapy (BNCT) requires high, tumor-selective boron delivery, yet carboranes, boron-rich BNCT building blocks, often suffer from poor aqueous solubility and suboptimal in vivo behavior despite exceptional boron density and stability. We report a modular star-shaped poly(2-oxazoline) (POx) scaffold that carries a high carborane payload and can be followed by positron emission tomography (PET). An alkyne-bearing POx was conjugated with azidopropyl meta-carborane, yielding PBMM-mCB20-EIP that remained highly water-soluble (225 g/L, ∼26 g/L of boron, 20 carboranes/star). PBMM-mCB20-EIP exhibited good cytocompatibility in CAL 27 and FaDu head-and-neck cancer cells and showed higher cell-associated boron concentration than the clinical agent sodium borocaptate. A DOTA-modified analogue was prepared and radiolabeled with gallium-68 for PET imaging. In healthy mice, gallium-68-labeled DOTA-PBMM-mCB20 revealed substantial blood-pool activity (17%ID/g) at 90 min, predominant renal clearance, and low background uptake, providing a baseline for further macromolecular engineering of this carrier and irradiation-timing optimization in tumor models.
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Hydroboration-Oxidation of Alkenes
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Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.

