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Award ID contains: 2102225

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  1. Two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy was evaluated for the identification and quantification of compounds in an unknown street drug sample. Using 2D COSY and HSQC techniques, heroin was successfully quantified, and the presence of 6-monoacetylmorphine (6-MAM), xylazine, and caffeine was confirmed through partial structural elucidation. These methods demonstrated the ability to differentiate structurally similar opioid analogues without reliance on reference library databases. While gas chromatography–mass spectrometry (GC–MS) remains the standard in forensic laboratories, it has limitations in de novo structural analysis and in detecting emerging analogues absent from spectral libraries. In this study, heroin and fentanyl were quantified in both simulated and actual street samples at concentrations ranging from 0.97 to 1.80 mg/mL, with errors between 0% and 34% using a 400 MHz NMR instrument. A benchtop 60 MHz NMR system also detected and quantified 56 mg/mL of heroin with a 24% error in a simulated sample. These findings support the complementary role of 2D NMR spectroscopy in forensic drug analysis in light of the opioid epidemic and the evolving drug market. 
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    Free, publicly-accessible full text available July 25, 2026
  2. Silverman, Scott (Ed.)
    The employment of antibodies as a targeted drug delivery vehicle has proven successful which is exemplified by the emergence of antibody–drug conjugates (ADCs). However, ADCs are not without their shortcomings. Improvements may be made to the ADC platform by decoupling the cytotoxic drug from the delivery vehicle and conjugating an organometallic catalyst in its place. The resulting protein–metal catalyst conjugate was designed to uncage the masked cytotoxin administered as a separate entity. Macropinocytosis of albumin by cancerous cells suggests the potential of albumin acting as the tumor-targeting delivery vehicle. Herein reported are the first preparation and demonstration of ruthenium catalysts with cyclopentadienyl and quinoline-based ligands conjugated to albumin. The effective uncaging abilities were demonstrated on allyloxy carbamate (alloc)-protected rhodamine 110 and doxorubicin, providing a promising catalytic scaffold for the advancement of selective drug delivery methods in the future. 
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  3. Tyrosinase, an important oxidase involved in the primary immune response in humans, can sometimes become problematic as it can catalyze undesirable oxidation reactions. Therefore, for decades there has been a strong pharmaceutical interest in the discovery of novel inhibitors of this enzyme. Recent studies have also indicated that tyrosinase inhibitors can potentially be used in the treatment of melanoma cancer. Over the years, many new tyrosinase inhibitors have been discovered from various natural sources; however, marine natural products (MNPs) have contributed only a small number of promising candidates. Therefore, in this study we focused on the discovery of new MNP tyrosinase inhibitors of marine cyanobacterial and algal origins. A colorimetric tyrosinase inhibitory assay was used to screen over 4,500 marine extracts against mushroom tyrosinase ( A. bisporus ). Our results revealed that scytonemin monomer (ScyM), a pure compound from our compound library and also the monomeric last-step precursor in the biosynthesis of the well-known cyanobacterial sunscreen pigment “scytonemin,” consistently showed the highest tyrosinase inhibitory score. Determination of the half maximal inhibitory concentration (IC 50 ) further indicated that ScyM is more potent than the commonly used commercial inhibitor standard “kojic acid” (KA; IC 50 of ScyM: 4.90 μM vs. IC 50 of KA: 11.31 μM). After a scaled-up chemical synthesis of ScyM as well as its O -methyl analog (ScyM-OMe), we conducted a series of follow-up studies on their structures, inhibitory properties, and mode of inhibition. Our results supported ScyM as the second case ever of a novel tyrosinase inhibitory compound based on a marine cyanobacterial natural product. The excellent in vitro performance of ScyM makes it a promising candidate for applications such as a skin-whitening agent or an adjuvant therapy for melanoma cancer treatment. 
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