Nicotinamide phosphoribosyltransferase (Nampt) is an intriguing target for the treatment of many diseases, including cancer. Previously, our group demonstrated that carborane clusters may be used to increase the potency of small molecule inhibitors of Nampt over other, similarly sized organic moieties. Herein, we report a greatly improved, gram-scale synthesis of our most potent agent: 1-(4′-(trans-3″-(3‴-pyridyl) acrylamide)butyl)-1,7-dicarba-closo-dodecaborane (MC4-PPEA). Additionally, the carborane moiety of the molecule has been modified with a hydroxymethyl functional group to allow for its covalent attachment to targeted prodrugs, the synthesis of which are underway. Using cell viability assays, we demonstrate that this new derivative exhibits low, to mid-nanomolar potencies against human breast cancer cell lines in vitro.

•The first direct conversion solid-state neutron detector by combining the 10B with sub-2 nm Pt NP in MOSCAP structures.•Resolve the e–h separation challenge in direct conversion architectures by embedding Pt NPs as charge trap centers.•Both single and dual Pt NP layer embedded architectures, with varying electron addition energies, were studied.•Dual Pt NP layer embedded devices with higher electron addition energy are shown to successfully capture charges.We report a direct conversion solid-state neutron detection device fabricated by combining the large neutron capture cross-section of 10B with the charge trapping attributes of sub-2 nm Pt nanoparticles (Pt NPs) in MOSCAP structures. The 10B embedded polystyrene based neutron conversion layer also serves as the dielectric layer. Neutron sensing is achieved through carrier generation within the active 10B based dielectric layer and subsequent transfer to the embedded Pt NP layers, resulting in a significant change of the device's flat-band voltage upon ex-situ characterization. Both single and dual Pt NP layer embedded architectures, with varying electron addition energies, were tested within this study. While dual-layer Pt NPs embedded direct conversion devices with higher electron addition energy are shown to successfully capture charges generated through energetic reaction product upon neutron capture, the single Pt NP layer embedded device structure with lower electron addition energy displays signs of charge loss attributable to direct tunneling in the ex-situ capacitance–voltage measurement. Although only ex-situ detector operation is demonstrated within the realms of this study, sensitive in-situ neutron detectors and ultra-stable ex-situ dosimeters may be achievable utilizing a similar structure by fine-tuning the Pt NP size and the number of Pt NP layers in the device.

The association constants (\(\text{K}_{\text{a}}^{\prime }\)) of unsubstituted o-, m-, and p-carborane, as well as that of adamantane, with β-Cyclodextrin are reported for the first time using displacement binding in an aqueous solution. The \(\text{K}_{\text{a}}^{\prime }\) of several derivatives of these species are reported as well. The limitations of the displacement binding technique are also explored. Although hydrophobicity plays a major role in the association with β-CD, unsubstituted o-carborane, which is the least hydrophobic of the carborane derivatives, exhibits the highest \(\text{K}_{\text{a}}^{\prime }\) of 2690 M−1. The \(\text{K}_{\text{a}}^{\prime }\) values for the m- and p-carborane isomers decrease with decreasing dipole moment (1830 M−1 and 1560 M−1 respectively). Unsubstituted adamantane exhibits a \(\text{K}_{\text{a}}^{\prime }\) value lower than each of the three carborane isomers at 1410 M−1.

Herein we report the use of carboranes to significantly increase the potency of small molecule inhibitors of nicotinamide phosphoribosyltranferase (Nampt), an enzyme that is central to metabolism and cell survival. We compare the inclusion of carborane with other similarly sized substituents and demonstrate that, compared with their purely organic counterparts, these molecules exhibit up to 10-fold greater antiproliferative activity against cancer cells in vitro and a 100-fold increase in Nampt inhibition.