Search for: All records

Octreotide acetate, the active pharmaceutical ingredient in the long‐acting release (LAR) drug product Sandostatin®, is a cyclic octapeptide that mimics the naturally occurring somatostatin peptide hormone. Modern NMR can be a robust analytical method to identify and quantify octreotide molecules. Previous¹H chemical shift assignments were mostly performed in organic solvents, and no assignments for heteronuclear¹³C,¹⁵N, and aromatic¹H nuclei are available. Here, using state‐of‐the‐art 1D and 2D homo‐ and heteronuclear NMR experiments, octreotide was fully assigned, including water exchangeable amide protons, in aqueous buffer except for¹³CO and¹⁵NH of F1,¹⁵NH of C2, and¹⁵NζHζof K5 that were not observed because of water exchange or conformational exchange. The solution NMR spectra were then directly compared with 1D¹H/¹³C/¹⁵N solid‐state NMR (SSNMR) spectra showing the potential applicability of¹³C/¹⁵N SSNMR for octreotide drug product characterization.

Invasive species are a major threat to global biodiversity, yet also represent large‐scale unplanned ecological and evolutionary experiments to address fundamental questions in nature. Here we analyzed both native and invasive populations of predatory northern pike (Esox lucius) to characterize landscape genetic variation, determine the most likely origins of introduced populations, and investigate a presumably postglacial population from Southeast Alaska of unclear provenance. Using a set of 4329 SNPs from 351 individual Alaskan northern pike representing the most widespread geographic sampling to date, our results confirm low levels of genetic diversity in native populations (average 𝝅 of 3.18 × 10⁻⁴) and even less in invasive populations (average 𝝅 of 2.68 × 10⁻⁴) consistent with bottleneck effects. Our analyses indicate that invasive northern pike likely came from multiple introductions from different native Alaskan populations and subsequently dispersed from original introduction sites. At the broadest scale, invasive populations appear to have been founded from two distinct regions of Alaska, indicative of two independent introduction events. Genetic admixture resulting from introductions from multiple source populations may have mitigated the negative effects associated with genetic bottlenecks in this species with naturally low levels of genetic diversity. Genomic signatures strongly suggest an excess of rare, population‐specific alleles, pointing to a small number of founding individuals in both native and introduced populations consistent with a species' life history of limited dispersal and gene flow. Lastly, the results strongly suggest that a small isolated population of pike, located in Southeast Alaska, is native in origin rather than stemming from a contemporary introduction event. Although theory predicts that lack of genetic variation may limit colonization success of novel environments, we detected no evidence that a lack of standing variation limited the success of this genetically depauperate apex predator.

A facile and efficient two‐step synthesis ofp‐substituted tris(2‐pyridylmethyl)amine (TPMA) ligands to form Cu complexes with the highest activity to date in atom transfer radical polymerization (ATRP) is presented. In the divergent synthesis,p‐Cl substituents in tris(4‐chloro‐2‐pyridylmethyl)amine (TPMA^3Cl) were replaced in one step and high yield by electron‐donating cyclic amines (pyrrolidine (TPMA^PYR), piperidine (TPMA^PIP), and morpholine (TPMA^MOR)) by nucleophilic aromatic substitution. The [Cu^II(TPMA^NR2)Br]⁺complexes exhibited larger energy gaps between frontier molecular orbitals and >0.2 V more negative reduction potentials than [Cu^II(TPMA)Br]⁺, indicating >3 orders of magnitude higher ATRP activity. [Cu^I(TPMA^PYR)]⁺exhibited the highest reported activity for Br‐capped acrylate chain ends in DMF, and moderate activity toward C−F bonds at room temperature. ATRP ofn‐butyl acrylate using only 10–25 part per million loadings of [Cu^II(TPMA^NR2)Br]⁺exhibited excellent control.

A facile and efficient two‐step synthesis ofp‐substituted tris(2‐pyridylmethyl)amine (TPMA) ligands to form Cu complexes with the highest activity to date in atom transfer radical polymerization (ATRP) is presented. In the divergent synthesis,p‐Cl substituents in tris(4‐chloro‐2‐pyridylmethyl)amine (TPMA^3Cl) were replaced in one step and high yield by electron‐donating cyclic amines (pyrrolidine (TPMA^PYR), piperidine (TPMA^PIP), and morpholine (TPMA^MOR)) by nucleophilic aromatic substitution. The [Cu^II(TPMA^NR2)Br]⁺complexes exhibited larger energy gaps between frontier molecular orbitals and >0.2 V more negative reduction potentials than [Cu^II(TPMA)Br]⁺, indicating >3 orders of magnitude higher ATRP activity. [Cu^I(TPMA^PYR)]⁺exhibited the highest reported activity for Br‐capped acrylate chain ends in DMF, and moderate activity toward C−F bonds at room temperature. ATRP ofn‐butyl acrylate using only 10–25 part per million loadings of [Cu^II(TPMA^NR2)Br]⁺exhibited excellent control.