Showing papers by "Nathan C. Gianneschi published in 2018"
TL;DR: Two-dimensional covalent organic frameworks (2D COFs) offer broad monomer scope but are generally isolated as powders comprising aggregated nanometer-scale crystallites, but it is found that 2D COF formation could be controlled using a two-step procedure in which monomers are added slowly to preformed nanoparticle seeds, which should enable a broad exploration of synthetic 2D polymer structures and properties.
Abstract: Polymerization of monomers into periodic two-dimensional networks provides structurally precise, layered macromolecular sheets that exhibit desirable mechanical, optoelectronic, and molecular transport properties. Two-dimensional covalent organic frameworks (2D COFs) offer broad monomer scope but are generally isolated as powders comprising aggregated nanometer-scale crystallites. We found that 2D COF formation could be controlled using a two-step procedure in which monomers are added slowly to preformed nanoparticle seeds. The resulting 2D COFs are isolated as single-crystalline, micrometer-sized particles. Transient absorption spectroscopy of the dispersed COF nanoparticles revealed improvement in signal quality by two to three orders of magnitude relative to polycrystalline powder samples, and suggests exciton diffusion over longer length scales than those obtained through previous approaches. These findings should enable a broad exploration of synthetic 2D polymer structures and properties.
402 citations
Journal Article•
TL;DR: A feasible solution for producing structural colors inspired by bird feathers is demonstrated using a one-pot reverse emulsion process and with the combination of only two ingredients, synthetic melanin and silica, it can generate a full spectrum of colors.
131 citations
TL;DR: It is demonstrated that nanoparticle formation can be visualized in situ and that in the presence of excess monomer, nanoparticle growth occurs to yield sizes and morphologies consistent with standard PISA conditions.
Abstract: In this paper, we describe the use of liquid cell transmission electron microscopy (LCTEM) for inducing and imaging the formation of spherical micelles from amphiphilic block copolymers. Within the irradiated region of the liquid cell, diblock copolymers were produced which self-assembled, yielding a targeted spherical micellar phase via polymerization-induced self-assembly (PISA). Critically, we demonstrate that nanoparticle formation can be visualized in situ and that in the presence of excess monomer, nanoparticle growth occurs to yield sizes and morphologies consistent with standard PISA conditions. Experiments were enabled by employing automated LCTEM sample preparation and by analyzing LCTEM data with multi-object tracking algorithms designed for the detection of low-contrast materials.
78 citations
TL;DR: This Account seeks to open a discussion on the topic of standardizing strategies for conducting imaging experiments with a view to characterizing dynamics and motion of nanoscale materials, similar to doing chemistry in a lightning storm.
Abstract: Revolutions in science and engineering frequently result from the development, and wide adoption, of a new, powerful characterization or imaging technique. Beginning with the first glass lenses and telescopes in astronomy, to the development of visual-light microscopy, staining techniques, confocal microscopy, and fluorescence super-resolution microscopy in biology, and most recently aberration-corrected, cryogenic, and ultrafast (4D) electron microscopy, X-ray microscopy, and scanning probe microscopy in nanoscience. Through these developments, our perception and understanding of the physical nature of matter at length-scales beyond ordinary perception have been fundamentally transformed. Despite this progression in microscopy, techniques for observing nanoscale chemical processes and solvated/hydrated systems are limited, as the necessary spatial and temporal resolution presents significant technical challenges. However, the standard reliance on indirect or bulk phase characterization of nanoscale samples in liquids is undergoing a shift in recent times with the realization ( Williamson et al. Nat. Mater . 2003 , 2 , 532 - 536 ) of liquid-cell (scanning) transmission electron microscopy, LC(S)TEM, where picoliters of solution are hermetically sealed between electron-transparent "windows," which can be directly imaged or videoed at the nanoscale using conventional transmission electron microscopes. This Account seeks to open a discussion on the topic of standardizing strategies for conducting imaging experiments with a view to characterizing dynamics and motion of nanoscale materials. This is a challenge that could be described by critics and proponents alike, as analogous to doing chemistry in a lightning storm; where the nature of the solution, the nanomaterial, and the dynamic behaviors are all potentially subject to artifactual influence by the very act of our observation.
76 citations
TL;DR: Aqueous-phase ring-opening metathesis polymerization-induced self-assembly (ROMPISA) was used in this paper for forming micellar polymer nanoparticles at room temperature and high solids concentration.
Abstract: We report aqueous-phase Ring-Opening Metathesis Polymerization-Induced Self-Assembly (ROMPISA) for forming well-defined micellar polymer nanoparticles at room temperature and high solids concentration (20 w/w%). This is achieved with a new polymerization initiator, in the form of a water-soluble cationic Hoveyda-Grubbs second generation catalyst. This reaction was used in water to produce diblock copolymers from norbornenyl monomers, which then self-assemble into myriad nanostructure morphologies for which a phase diagram was constructed. Additionally, the living nature of the polymerization initiated by the aqueous initiator was confirmed, as shown by kinetic evaluation under mild conditions in water.
57 citations
TL;DR: A hybrid method combining machine learning and experimental testing for fast optimization of peptides for specific, orthogononal functions is developed and demonstrated that machine learning can be leveraged to guide peptide optimization for specific biochemical functions not immediately accessible by biological screening techniques.
Abstract: The discovery of peptide substrates for enzymes with exclusive, selective activities is a central goal in chemical biology. In this paper, we develop a hybrid computational and biochemical method to rapidly optimize peptides for specific, orthogonal biochemical functions. The method is an iterative machine learning process by which experimental data is deposited into a mathematical algorithm that selects potential peptide substrates to be tested experimentally. Once tested, the algorithm uses the experimental data to refine future selections. This process is repeated until a suitable set of de novo peptide substrates are discovered. We employed this technology to discover orthogonal peptide substrates for 4'-phosphopantetheinyl transferase, an enzyme class that covalently modifies proteins. In this manner, we have demonstrated that machine learning can be leveraged to guide peptide optimization for specific biochemical functions not immediately accessible by biological screening techniques, such as phage display and random mutagenesis.
53 citations
TL;DR: Detailed characterization by several analytical methods reveal that metal ion deposition on the surface of these MOFs occurs in the form of nanoscale metal oxides, rather than yielding exchanged metal sites within the MOFs, as was previously reported.
Abstract: Postsynthetic strategies for modifying metal-organic frameworks (MOFs) have proven to be an incredibly powerful approach for expanding the scope and functionality of these materials. Previously, we reported on the postsynthetic exchange (PSE) of metal ions and ligands in the University of Oslo (UiO) series of MOFs. Detailed characterization by several analytical methods, most notably inductively coupled plasma mass spectrometry and transmission electron microscopy reveal that metal ion deposition on the surface of these MOFs occurs in the form of nanoscale metal oxides, rather than yielding exchanged metal sites within the MOFs, as was previously reported. By contrast, these combined analytical methods do confirm that ligand-based PSE can occur in these MOFs. These findings provide new insight into the postsynthetic manipulation of MOF materials, highlight the importance of rigorously characterizing these materials to correctly assign their composition and structure, and provide a new route to making hybrid solids with a MOF@metal oxide architecture.
50 citations
TL;DR: The physical form of the natural spidroin precursor nanostructures stored within spider glands that seed the formation of their silks are determined and the fundamental structural transformations that occur during the initial stages of extrusion en route to fiber formation are revealed.
Abstract: Many natural silks produced by spiders and insects are unique materials in their exceptional toughness and tensile strength, while being lightweight and biodegradable–properties that are currently unparalleled in synthetic materials. Myriad approaches have been attempted to prepare artificial silks from recombinant spider silk spidroins but have each failed to achieve the advantageous properties of the natural material. This is because of an incomplete understanding of the in vivo spidroin-to-fiber spinning process and, particularly, because of a lack of knowledge of the true morphological nature of spidroin nanostructures in the precursor dope solution and the mechanisms by which these nanostructures transform into micrometer-scale silk fibers. Herein we determine the physical form of the natural spidroin precursor nanostructures stored within spider glands that seed the formation of their silks and reveal the fundamental structural transformations that occur during the initial stages of extrusion en route to fiber formation. Using a combination of solution phase diffusion NMR and cryogenic transmission electron microscopy (cryo-TEM), we reveal direct evidence that the concentrated spidroin proteins are stored in the silk glands of black widow spiders as complex, hierarchical nanoassemblies (∼300 nm diameter) that are composed of micellar subdomains, substructures that themselves are engaged in the initial nanoscale transformations that occur in response to shear. We find that the established micelle theory of silk fiber precursor storage is incomplete and that the first steps toward liquid crystalline organization during silk spinning involve the fibrillization of nanoscale hierarchical micelle subdomains.
39 citations
TL;DR: NanoSIMS and NanoSIMS are concluded that these techniques are powerful for the elucidation of the localization of cargo and carrier, and enable a high-resolution assessment of their performance following in vivo delivery.
Abstract: In nanomedicine, determining the spatial distribution of particles and drugs, together and apart, at high resolution within tissues, remains a major challenge because each must have a different label or detectable feature that can be observed with high sensitivity and resolution. We prepared nanoparticles capable of enzyme-directed assembly of particle therapeutics (EDAPT), containing an analogue of the Pt(II)-containing drug oxaliplatin, an 15N-labeled monomer in the hydrophobic block of the backbone of the polymer, the near-infrared dye Cy5.5, and a peptide that is a substrate for tumor metalloproteinases in the hydrophilic block. When these particles reach an environment rich in tumor associated proteases, the hydrophilic peptide substrate is cleaved, causing the particles to accumulate through a morphology transition, locking them in the tumor extracellular matrix. To evaluate the distribution of drug and EDAPT carrier in vivo, the localization of the isotopically labeled polymer backbone was compared to that of Pt by nanoscale secondary ion mass spectrometry (NanoSIMS). The correlation of NanoSIMS with super-resolution fluorescence microscopy revealed the release of the drug from the nanocarrier and colocalization with cellular DNA within tumor tissue. The results confirmed the dependence of particle accumulation and Pt(II) drug delivery on the presence of a Matrix Metalloproteinase (MMP) substrate and demonstrated antitumor activity. We conclude that these techniques are powerful for the elucidation of the localization of cargo and carrier, and enable a high-resolution assessment of their performance following in vivo delivery.
35 citations
TL;DR: Novel RNA-polymer amphiphiles that assemble into spherical micellar nanoparticles with diameters of ca.
27 citations
TL;DR: The synthesis of two homopolymers with mesogenic side chains that can be cleaved upon exposure to either H2 O2 ( polymer P1) or UV light (polymer P2) validate a simple and generalizable approach to the rational design of polymers that can been used to program stimuli-responsiveness into LC materials.
Abstract: Liquid crystals (LCs) offer the basis of stimuli-responsive materials that can amplify targeted molecular events into macroscopic outputs. However, general and versatile design principles are needed to realize the full potential of these materials. To this end, we report the synthesis of two homopolymers with mesogenic side chains that can be cleaved upon exposure to either H2 O2 (polymer P1) or UV light (polymer P2). Optical measurements reveal that the polymers dissolve in bulk LC and spontaneously assemble at nematic LC-aqueous interfaces to impose a perpendicular orientation on the LCs. Subsequent addition of H2 O2 to the aqueous phase or exposure of the LC to UV was shown to trigger a surface-driven ordering transition to a planar orientation and an accompanying macroscopic optical output. Differences in the dynamics of the response to each stimulus are consistent with sequential processing of P1 at the LC-aqueous interface (H2 O2 ) and simultaneous transformation of P2 within the LC (UV). The versatility of the approach is demonstrated by creating stimuli-responsive LCs as films or microdroplets, and by dissolving mixtures of P1 and P2 into LCs to create LC materials that respond to two stimuli. Overall, our results validate a simple and generalizable approach to the rational design of polymers that can be used to program stimuli-responsiveness into LC materials.
TL;DR: In this article, the authors report the synthesis of families of amphiphilic polymers that differ in (i) side-chain molecular structure, (ii) polymer architecture, and (iii) copolymer composition.
Abstract: Interfacial assemblies formed by polymeric amphiphiles at aqueous interfaces of thermotropic liquid crystals (LCs) can trigger multiscale changes in the organization of the LCs in response to recognition events. However, we have a limited understanding of the rules governing the rational design of LC-integrated polymeric amphiphiles. Herein, we report the synthesis of families of amphiphilic polymers that differ in (i) side-chain molecular structure, (ii) polymer architecture, and (iii) copolymer composition. We used this library in experiments to establish structure–property relationships relevant to the design of multifunctional polymers that can amplify and transduce biomolecular recognition events into optically detectable, macroscopic ordering transitions in LCs. We then utilized these structure–property relationships to guide the design of a peptide–polymer amphiphile (PPA) that assembles at the interface of LC droplets. Enzymatic cleavage of PPA-coated LC droplets by thermolysin directly triggered ...
TL;DR: Lipophilic indocarbocyanine anchors are a promising technology for incorporation of biomolecules and small molecules into biological membranes for in vivo applications.
TL;DR: A lipid-coated polymer gel (lipogel) formulated using a single-pot methodology, where self-assembling liposomes template a UV-curable polymer gel core, which holds potential as a tunable nanomaterial scaffold.
TL;DR: Leriche et al. as mentioned in this paper reported the synthesis of a new archaea-inspired tetraether lipid and study the mechanical elastic properties of membranes made from this bolalipid.
Abstract: Author(s): Leriche, G; Manafirad, A; Nguyen, S; Bell, N; Patterson, JP; Thayumanavan, S; Yang, J; Dinsmore, AD; Gianneschi, NC | Abstract: Researchers report the synthesis of a new archaea-inspired tetraether lipid and study the mechanical elastic properties of membranes made from this bolalipid. To access structural diversity in the hydrophobic moiety of the lipids and to tune membrane properties, they have used used Huisgen 1,3-dipolar cycloaddition strategy to design and synthesize a tetraether lipid incorporating phytanyl side chains and polar 1,4 triazole rings known to change lipid packing. The researchers demonstrate the first example of the synthesis of phytanyl side chain incorporated tetraether lipids with 1,4-triazole rings. They also confirm the ability of lipids incorporating 1,4-triazole rings to form stable small and giant vesicles and examined their physical and mechanical properties using a micropipette aspiration technique.
TL;DR: In this paper, the authors present a survey of the chemistry and biochemistry departments at the University of California, San Diego and Northwestern University in the US, focusing on the use of multiscale electron microscopy.
Abstract: 1. Department of Chemistry, Department of Materials Science and Engineering, and Department of Biomedical Engineering, Northwestern University, Evanston, USA. 2. Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, USA. 3. Laboratory of Materials and Interface Chemistry and Center of Multiscale Electron Microscopy, Department of Chemical Engineering, Eindhoven University of Technology, Eindhoven, NL. 4. SuperSTEM Laboratory, SciTech Daresbury Campus, Daresbury, UK.
TL;DR: In this article, the authors proposed a method for using multiscale Electron Microscopy (MEMC) to study the properties and properties of high-dimensional materials.
Abstract: 1. Department of Chemistry, Department of Materials Science and Engineering, and Department of Biomedical Engineering, Northwestern University, Evanston, USA. 2. Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, USA. 3. Laboratory of Materials and Interface Chemistry and Center of Multiscale Electron Microscopy, Department of Chemical Engineering, Eindhoven University of Technology, Eindhoven, NL.
Patent•
27 Sep 2018
TL;DR: The present disclosure generally provides compounds useful for treating cancer as discussed by the authors, including compounds that are chemically modified to have one or more moieties that include hydrophobic portions, and compositions that include modified peptides and another protein, such as albumin or albumin mimetics.
Abstract: The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides containing compounds that are chemically modified to have one or more moieties that include hydrophobic portions. In some aspects, the disclosure provides compositions that include such modified peptides and another protein, such as albumin or albumin mimetics. Further, the disclosure provides various uses of these compounds and compositions.
Patent•
27 Sep 2018
TL;DR: The present disclosure generally provides compounds useful for treating cancer as discussed by the authors, and in some aspects, the disclosure provides compositions that include such modified platinum compounds and a protein, such as albumin or albumin mimetics.
Abstract: The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides platinum compounds that are chemically modified to have one or more moieties that include hydrophobic portions. In some aspects, the disclosure provides compositions that include such modified platinum compounds and a protein, such as albumin or albumin mimetics. Further, the disclosure provides various uses of these compounds and compositions.
Patent•
27 Sep 2018
TL;DR: In this article, the disclosure provides small-molecule histone deacetylase inhibitors (HDIs) that are chemically modified to have one or more moieties that include hydrophobic portions.
Abstract: The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides small-molecule histone deacetylase inhibitors (HDIs) that are chemically modified to have one or more moieties that include hydrophobic portions. In some aspects, the disclosure provides compositions that include such modified HDIs and a protein, such as albumin or albumin mimetics. Further, the disclosure provides various uses of these compounds and compositions.
Patent•
11 Jun 2018TL;DR: Cyclic peptide pro-gelator compositions, and methods of therapeutic use, which assemble into macromolecular hydrogel when administered through cleavage by endogenous enzymes upregulated at a site of tissue injury, such as a myocardial infarction, are discussed in this article.
Abstract: Cyclic peptide pro-gelator compositions, and methods of therapeutic use, which assemble into macromolecular hydrogel when administered through cleavage by endogenous enzymes upregulated at a site of tissue injury, such as a myocardial infarction.
Patent•
27 Sep 2018
TL;DR: The present disclosure generally provides compounds useful for treating cancer In some aspects, the disclosure provides anthracycline compounds that are chemically modified to have one or more moieties that include hydrophobic portions.
Abstract: The present disclosure generally provides compounds useful for treating cancer In some aspects, the disclosure provides anthracycline compounds that are chemically modified to have one or more moieties that include hydrophobic portions In some aspects, the disclosure provides compositions that include such modified amrubicin compounds and a protein, such as albumin or albumin mimetics Further, the disclosure provides various uses of these compounds and compositions