Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (7 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2023)

Chapter 1. This section presents an overview of literature pertaining to low-valent/low-oxidation state tin hydrides, transition metal coordinated tin hydrides, and group 10 trinuclear metal cluster synthesis, characterization, and reactivity. Chapter 2. Treatment of the trichlorotin-capped trinuclear nickel cluster, [Ni3(dppm)3(μ3-Cl)(μ3-SnCl3)], 1, with 4 eq. NaHB(Et)3 yields a μ3-SnH capped trinuclear nickel cluster, [Ni3(dppm)3(μ3-H)(μ3-SnH)], 2 [dppm = bis(diphenylphosphino)methane]. Single-crystal X-ray diffraction, nuclear magnetic resonance (NMR) spectroscopy, and computational studies together support that cluster 2 is a divalent tin hydride. Complex 2 displays a wide range of reactivity including oxidative addition of bromoethane across the Sn center. Addition of 1 eq. iodoethane to complex 2 releases H2 (g) and generates an ethyltin-capped nickel cluster with a μ3-iodide, [Ni3(dppm)3(μ3-I)(μ3-Sn(CH2CH3))], 4. Notably, insertion of alkynes into the Sn–H bond of 2 can be achieved via addition of 1 eq. 1-hexyne to generate the 1-hexen-2-yl-tin-capped nickel cluster, [Ni3(dppm)3(μ3H)(μ3-Sn(C6H11))], 5. Addition of H2 (g) to 5 regenerates the starting material, 2, and hexane. The formally 44-electron cluster 2 also displays significant redox chemistry with two reversible one-electron oxidations (E = −1.3 V, −0.8 V vs. Fc0/+) and one-electron reduction process (E = −2.7 V vs. Fc0/+) observed by cyclic voltammetry. Chapter 3. H2 and D2 exchange by a μ3-SnH, μ3-H capped trinuclear nickel cluster, [Ni3(dppm)3(μ3-H)(μ3-SnH)], 1, (dppm = bis(diphenylphosphino)methane) was investigated through a variety of nuclear magnetic resonance (NMR) spectroscopy studies. Mechanistic studies reveal reversible exchange upon addition of D2/H2 between 1 and the deuteride species, [Ni3(dppm)3(μ3-D)(μ3-SnD)], 1D. Furthermore, these studies suggest a conformational change at the Ni-H functionality upon addition of H2. Variable temperature (VT) NMR studies of 1 demonstrate a temperature dependence of the Sn-H and the Ni-H resonances, with the Ni-H experiencing the largest perturbation in chemical shift. Further mechanistic insights were obtained with VT NMR studies performed under an atmosphere H2 and HD. Overall, these studies provide evidence of H2/D2 exchange by complex 1 and suggest a novel mechanism for hydrogen activation and exchange processes. Chapter 4. Spectroscopic and structural comparisons are made between a series of (OR)3Sn capped trinuclear nickel clusters. The synthesis of the (OEt)3Sn and (OPh)3Sn capped nickel clusters, [Ni3(dppm)3(μ3-Cl)(μ3-Sn(OEt)3)] (1), [Ni3(dppm)3(μ3-Cl)(μ3-Sn(OPh)3)] (2), was realized by the treatment of [Ni3(dppm)3(μ3-Cl)(μ3-SnCl3] with 6 eq. of KOEt or NaOPh, respectively. Treatment of complex 1 with 10 eq. glycerol results in the synthesis of the (C3H5O3)Sn capped trinuclear nickel cluster, [Ni3(dppm)3(μ3-Cl)(μ3-Sn(C3H5O3))] (3). The crystallographic studies of these clusters allow a detailed structural comparison. In addition, cyclic voltammetric data were obtained for complexes 1, 2, and 3 and their electrochemical properties are compared. Complex 1 and 3 exhibit reversible oxidation and reduction events. Complex 2 displays a reversible oxidation and a pseudo-reversible reduction. Chapter 5. The focus of this chapter is to briefly describe project ideas based on main group coordinated polynuclear clusters that future researchers may find worthwhile.

    Cover page: Synthesis, structure, and reactivity of µ3-Sn capped trinuclear nickel clusters
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2019)
    Rationale: Intraoperative visualization in small surgical cavities and hard-to-access areas are essential requirements for modern, minimally invasive surgeries and demand significant miniaturization. However, current optical imagers require multiple hard-to-miniaturize components including lenses, filters and optical fibers. These components restrict both the form-factor and maneuverability of these imagers, and imagers largely remain stand-alone devices with centimeter-scale dimensions. Methods: We have engineered INSITE (Immunotargeted Nanoparticle Single-Chip Imaging Technology), which integrates the unique optical properties of lanthanide-based alloyed upconverting nanoparticles (aUCNPs) with the time-resolved imaging of a 25-micron thin CMOS-based (complementary metal oxide semiconductor) imager. We have synthesized core/shell aUCNPs of different compositions and imaged their visible emission with INSITE under either NIR-I and NIR-II photoexcitation. We characterized aUCNP imaging with INSITE across both varying aUCNP composition and 980 nm and 1550 nm excitation wavelengths. To demonstrate clinical experimental validity, we also conducted an intratumoral injection into LNCaP prostate tumors in a male nude mouse that was subsequently excised and imaged with INSITE. Results: Under the low illumination fluences compatible with live animal imaging, we measure aUCNP radiative lifetimes of 600 μs - 1.3 ms, which provides strong signal for time-resolved INSITE imaging. Core/shell NaEr0.6Yb0.4F4 aUCNPs show the highest INSITE signal when illuminated at either 980 nm or 1550 nm, with signal from NIR-I excitation about an order of magnitude brighter than from NIR-II excitation. The 55 μm spatial resolution achievable with this approach is demonstrated through imaging of aUCNPs in PDMS (polydimethylsiloxane) micro-wells, showing resolution of micrometer-scale targets with single-pixel precision. INSITE imaging of intratumoral NaEr0.8Yb0.2F4 aUCNPs shows a signal-to-background ratio of 9, limited only by photodiode dark current and electronic noise. Conclusion: This work demonstrates INSITE imaging of aUCNPs in tumors, achieving an imaging platform that is thinned to just a 25 μm-thin, planar form-factor, with both NIR-I and NIR-II excitation. Based on a highly paralleled array structure INSITE is scalable, enabling direct coupling with a wide array of surgical and robotic tools for seamless integration with tissue actuation, resection or ablation.
      Cover page: A 25 micron-thin microscope for imaging upconverting nanoparticles with NIR-I and NIR-II illumination
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2019)
      Rationale: Intraoperative visualization in small surgical cavities and hard-to-access areas are essential requirements for modern, minimally invasive surgeries and demand significant miniaturization. However, current optical imagers require multiple hard-to-miniaturize components including lenses, filters and optical fibers. These components restrict both the form-factor and maneuverability of these imagers, and imagers largely remain stand-alone devices with centimeter-scale dimensions. Methods: We have engineered INSITE (Immunotargeted Nanoparticle Single-Chip Imaging Technology), which integrates the unique optical properties of lanthanide-based alloyed upconverting nanoparticles (aUCNPs) with the time-resolved imaging of a 25-micron thin CMOS-based (complementary metal oxide semiconductor) imager. We have synthesized core/shell aUCNPs of different compositions and imaged their visible emission with INSITE under either NIR-I and NIR-II photoexcitation. We characterized aUCNP imaging with INSITE across both varying aUCNP composition and 980 nm and 1550 nm excitation wavelengths. To demonstrate clinical experimental validity, we also conducted an intratumoral injection into LNCaP prostate tumors in a male nude mouse that was subsequently excised and imaged with INSITE. Results: Under the low illumination fluences compatible with live animal imaging, we measure aUCNP radiative lifetimes of 600 μs - 1.3 ms, which provides strong signal for time-resolved INSITE imaging. Core/shell NaEr0.6Yb0.4F4 aUCNPs show the highest INSITE signal when illuminated at either 980 nm or 1550 nm, with signal from NIR-I excitation about an order of magnitude brighter than from NIR-II excitation. The 55 μm spatial resolution achievable with this approach is demonstrated through imaging of aUCNPs in PDMS (polydimethylsiloxane) micro-wells, showing resolution of micrometer-scale targets with single-pixel precision. INSITE imaging of intratumoral NaEr0.8Yb0.2F4 aUCNPs shows a signal-to-background ratio of 9, limited only by photodiode dark current and electronic noise. Conclusion: This work demonstrates INSITE imaging of aUCNPs in tumors, achieving an imaging platform that is thinned to just a 25 μm-thin, planar form-factor, with both NIR-I and NIR-II excitation. Based on a highly paralleled array structure INSITE is scalable, enabling direct coupling with a wide array of surgical and robotic tools for seamless integration with tissue actuation, resection or ablation.
        Cover page: A 25 micron-thin microscope for imaging upconverting nanoparticles with NIR-I and NIR-II illumination.
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2018)
          Cover page: Dicopper Alkyl Complexes: Synthesis, Structure, and Unexpected Persistence
          • Article
          • Peer Reviewed
          LBL Publications (2023)

          Purpose

          Intraoperative detection and removal of microscopic residual disease (MRD) remain critical to the outcome of cancer surgeries. Today's minimally invasive surgical procedures require miniaturization and surgical integration of highly sensitive imagers to seamlessly integrate into the modern clinical workflow. However, current intraoperative imagers remain cumbersome and still heavily dependent on large lenses and rigid filters, precluding further miniaturization and integration into surgical tools.

          Procedures

          We have successfully engineered a chip-scale intraoperative micro-imager array-without optical filters or lenses-integrated with lanthanide-based alloyed upconverting nanoparticles (aUCNPs) to achieve tissue imaging using a single micro-chip. This imaging platform is able to leverage the unique optical properties of aUCNPs (long luminescent lifetime, high-efficiency upconversion, no photobleaching) by utilizing a time-resolved imaging method to acquire images using a 36-by-80-pixel, 2.3 mm [Formula: see text] 4.8 mm silicon-based electronic imager micro-chip, that is, less than 100-µm thin. Each pixel incorporates a novel architecture enabling automated background measurement and cancellation. We have validated the performance, spatial resolution, and the background cancellation scheme of the imaging platform, using resolution test targets and mouse prostate tumor sample intratumorally injected with aUCNPs. To demonstrate the ability to image MRD, or tumor margins, we evaluated the imaging platform in visualizing a single-cell thin section of the injected prostate tumor sample.

          Results

          Tested on USAF resolution targets, the imager is able to achieve a resolution of 71 µm. We have also demonstrated successful background cancellation, achieving a signal-to-background ratio of 8 when performing ex vivo imaging on aUCNP-injected prostate tumor sample, improved from originally 0.4. The performance of the imaging platform on single-cell layer sections was also evaluated and the sensor achieved a signal-to-background ratio of 4.3 in resolving cell clusters with sizes as low as 200 cells.

          Conclusion

          The imaging system proposed here is a scalable chip-scale ultra-thin alternative for bulky conventional intraoperative imagers. Its novel pixel architecture and background correction scheme enable visualization of microscopic-scale residual disease while remaining completely free of lenses and filters, achieving an ultra-miniaturized form factor-critical for intraoperative settings.
            Cover page: Fully Integrated Ultra-thin Intraoperative Micro-imager for Cancer Detection Using Upconverting Nanoparticles
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2018)
            Multiphoton imaging techniques that convert low-energy excitation to higher energy emission are widely used to improve signal over background, reduce scatter, and limit photodamage. Lanthanide-doped upconverting nanoparticles (UCNPs) are among the most efficient multiphoton probes, but even UCNPs with optimized lanthanide dopant levels require laser intensities that may be problematic. Here, we develop protein-sized, alloyed UCNPs (aUCNPs) that can be imaged individually at laser intensities >300-fold lower than needed for comparably sized doped UCNPs. Using single UCNP characterization and kinetic modeling, we find that addition of inert shells changes optimal lanthanide content from Yb3+, Er3+-doped NaYF4 nanocrystals to fully alloyed compositions. At high levels, emitter Er3+ ions can adopt a second role to enhance aUCNP absorption cross-section by desaturating sensitizer Yb3+ or by absorbing photons directly. Core/shell aUCNPs 12 nm in total diameter can be imaged through deep tissue in live mice using a laser intensity of 0.1 W cm-2.
              Cover page: Low irradiance multiphoton imaging with alloyed lanthanide nanocrystals
              • Article
              • Peer Reviewed
              LBL Publications (2023)
              Liquid organic hydrogen carrier (LOHC) systems are an excellent alternative to pressurized gas and liquid hydrogen storage technologies due to their high volumetric storage capacities and straightforward adaptation to existing infrastructure. Homogeneous catalysts are promising for the selective and reversible release of hydrogen from LOHC. However, separation from product mixtures and recycling inhibit their use, particularly when comprised of costly low-abundance elements, motivating the development of heterogeneous versions that are more easily recovered and reused. Here, we describe two methods for the heterogenization of molecular Ru catalysts that efficiently dehydrogenate the polyalcohol LOHCs ethylene glycol (EG) and 1,2-propanediol (1,2-PDO). The heterogeneous versions of these catalysts maintain catalytic activity for hydrogen production comparable to the homogeneous complexes, with up to 81% conversion and 99% selectivity. DFT modeling indicates mechanistic similarities for the dehydrogenations of EG and 1,2-PDO, with the rate-limiting steps associated with protonation of the Ru-H bond to form H2 and the alkoxide species coordinated to Ru(II), followed by β-hydride elimination to regenerate the Ru-H bond. Overall, the data suggest these heterogenized molecular catalysts have potential for practical use in polyalcohol-based LOHC systems.
                Cover page: Heterogenization of Homogeneous Ruthenium(II) Catalysts for Carbon-Neutral Dehydrogenation of PolyalcoholsCreative Commons 'BY-NC' version 4.0 license
                Top