Key defining attributes of an antibody-drug conjugate (ADC) include the choice of the targeting antibody, linker, payload, and the drug-to-antibody ratio (DAR). Historically, most ADC platforms have used the same DAR for all targets, regardless of target characteristics. However, recent studies and modeling suggest that the optimal DAR can depend on target expression level and intratumoral heterogeneity, target internalization and trafficking, and characteristics of the linker and payload.
View Article and Find Full Text PDFThe synthesis and single crystal structures of Am(iii) and Cm(iii) thiocyanate complexes are reported along with an isostructural series of lanthanide thiocyanate complexes. Because the complexes are isostructural, a comparative study of the metal-thiocyanate bonds was conducted using Raman spectroscopy indicating very similar and electrostatic metal-ligand interactions.
View Article and Find Full Text PDFFive heteroleptic Cu(i)bis(phenanthroline) chromophores with distinct variation in the steric bulk at the 2,9-phenanthroline position were synthesized using the HETPHEN method, and their ground and excited state properties are described. Analysis of the crystal structures reveals a significant distortion from tetrahedral geometry around the Cu(i) centre which is attributed to favourable aromatic interactions between the two phenanthroline ligands. Ultrafast and nanosecond transient optical spectroscopies reveal that the excited state lifetime can be tuned across two orders of magnitude up to 74 nanoseconds in acetonitrile by changing the 2,9-substituent from hydrogen to sec-butyl.
View Article and Find Full Text PDFThis manuscript describes a combination of DFT calculations and experiments to assess the reduction of borazines (B-N heterocycles) by η-coordination to Cr(CO) or [Mn(CO)] fragments. The energy requirements for borazine reduction are established as well as the extent to which coordination of borazine to a transition metal influences hydride affinity, basicity, and subsequent reduction steps at the coordinated borazine molecule. Borazine binding to M(CO) fragments decreases the thermodynamic hydricity by >30 kcal mol, allowing it to easily accept a hydride.
View Article and Find Full Text PDFThe synthesis, X-ray crystal structure, vibrational and optical spectroscopy for the eight-coordinate thiocyanate compounds, [Et4 N]4 [Pu(IV) (NCS)8 ], [Et4 N]4 [Th(IV) (NCS)8 ], and [Et4 N]4 [Ce(III) (NCS)7 (H2 O)] are reported. Thiocyanate was found to rapidly reduce plutonium to Pu(III) in acidic solutions (pH<1) in the presence of NCS(-) . The optical spectrum of [Et4 N][SCN] containing Pu(III) solution was indistinguishable from that of aquated Pu(III) suggesting that inner-sphere complexation with [Et4 N][SCN] does not occur in water.
View Article and Find Full Text PDFBoron clusters are proposed as a new concept for the design of magnesium-battery electrolytes that are magnesium-battery-compatible, highly stable, and noncorrosive. A novel carborane-based electrolyte incorporating an unprecedented magnesium-centered complex anion is reported and shown to perform well as a magnesium-battery electrolyte. This finding opens a new approach towards the design of electrolytes whose likelihood of meeting the challenging design targets for magnesium-battery electrolytes is very high.
View Article and Find Full Text PDFMonoclonal antibodies (mAbs) are currently the dominant class of biopharmaceuticals. Due to the high dosage requirements of most mAb therapeutics, high productivity and low aggregation are prevailing criteria during cell line generation and process development. Given that light chains (LCs) play an important role in antibody folding and assembly, and that most mAb producing cell lines also manufacture free LCs, we sought to investigate whether there was a relationship between free LC levels in cell culture media and mAb productivity/quality.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2012
Recharging spent BN fuel: {Cr(CO)(3)} mediates the reduction of borazines by hydride and methyl nucleophiles to generate anionic complexes of dearomatized hexamethylborazine. Subsequent quenching leads to the release of a substituted cyclotriborazane, successfully demonstrating the stepwise reduction of a B=N bond.
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