A5070400538- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Crystallography and molecular interactions
- nanoparticles nucleation surface interactions
- Chemical Thermodynamics and Molecular Structure
- Innovative Microfluidic and Catalytic Techniques Innovation
- Chemistry and Chemical Engineering
- Metal-Organic Frameworks: Synthesis and Applications
- Drug Solubulity and Delivery Systems
- Spectroscopy and Quantum Chemical Studies
- Enzyme Structure and Function
- Multicomponent Synthesis of Heterocycles
- Surface Chemistry and Catalysis
- Thermal and Kinetic Analysis
- Chemical Synthesis and Reactions
- Chemical Synthesis and Analysis
- HIV/AIDS drug development and treatment
- Molecular Junctions and Nanostructures
- Immunodeficiency and Autoimmune Disorders
- Autoimmune and Inflammatory Disorders
- Phytochemical Studies and Bioactivities
- Computational Drug Discovery Methods
- Carbon dioxide utilization in catalysis
- Calcium Carbonate Crystallization and Inhibition
- CCD and CMOS Imaging Sensors
Merck & Co., Inc., Rahway, NJ, USA (United States)
2011-2025
CHA Gangnam Medical Center
2024
Illinois Institute of Technology
2002-2009
University of Hawaii System
2008
Korea Institute of Oriental Medicine
2008
GlaxoSmithKline (Netherlands)
2008
Novartis-MIT Center for Continuous Manufacturing
2008
Massachusetts Institute of Technology
2008
GlaxoSmithKline (United Kingdom)
2007
Astellas Pharma (United States)
2005
Crystallization is vital to many processes occurring in nature and the chemical, pharmaceutical, food industries. Notably, crystallization an attractive isolation step for manufacturing because this single process combines both particle formation purification. Almost all of products based on fine chemicals, such as dyes, explosives, photographic materials, require their manufacture, more than 90% pharmaceutical contain bioactive drug substances excipients crystalline solid state. Hence...
The physicochemical properties of molecular crystals, such as solubility, stability, compactability, melting behaviour and bioavailability, depend on their crystal form1. In silico form selection has recently come much closer to realization because the development accurate affordable free-energy calculations2-4. Here we redefine state art, primarily by improving accuracy calculations, constructing a reliable experimental benchmark for solid-solid differences, quantifying statistical errors...
Patterned glycine crystals nucleated on functionalized metallic square islands. This approach can be used to fabricate particles with micron dimensions and screen solid forms under different conditions. The size of the is controlled by High energy metastable β-glycine crystallizes small islands, whereas for large polymorphic outcome becomes biased toward α-form.
The solution-mediated phase transformation of the metastable A form an active pharmaceutical ingredient (1) to stable B is investigated in 2-propanol. behavior (or rate) quantified using powder X-ray diffraction. studies show that rate sensitive tailor-made impurities and presence certain inhibitors reduces transformation. Concurrently molecular modeling are undertaken investigate incorporation these structurally related into crystal lattice, it observed build-in approach used morphology...
Kristen Fichthorn opened the discussion of introductory lecture by James De Yoreo: I noted that in your potential mean force (PMF) plots for various particle orientations, fluctuations occur such different orientations could be preferred at a fixed distance. Could this affect ag
During the past three decades, ability of guanidinium arenesulfonate host frameworks to encapsulate a wide range guests has been amply demonstrated, with more than 700 inclusion compounds realized. Herein, we report crystalline based on new aliphatic host, cyclohexanemonosulfonate, which surprisingly exhibits four heretofore unobserved architectures, as described by projection topologies organosulfonate residues above and below hydrogen-bonded sulfonate sheets. The adopt layer motif sheets...
Single crystal X-ray diffraction (SCXRD) is arguably the most definitive method for molecular structure determination, but it often challenged by compounds that are liquids or oils at room temperature do not form crystals adequate analysis. Our laboratory previously reported a simple, cost-effective, single-step crystallization based on guanidinium organosulfonate (GS) hydrogen bonded frameworks determination of wide range encapsulated guest molecules, including assignment absolute...
This study demonstrates the effect of solution pH on polymorphic outcome glycine by evaporation-driven crystallization from aqueous solution. More than 2000 droplets under identical conditions were generated using a patterned self-assembled monolayers (SAMs) substrate. Each droplet substrate serves as an independent trial. Glycine nucleated inside through solvent evaporation, and their forms identified via Raman microscopy. Three different (α-, β-, γ-forms) simultaneously crystallized at all...
Small droplets of supersaturated hen egg white lysozyme (HEWL) solution were exposed to intense linearly polarized laser pulses with different wavelengths, intensities, and pulse durations. Laser irradiation under some conditions significantly increased the number in which crystals observed a given time period, compared nonirradiated samples. As general rule, nonphotochemical induced nucleation (NPLIN) solutions was more effective shorter aging time, 532-nm wavelength, higher peak intensity,...
Crystal structure prediction (CSP) is an invaluable tool in the pharmaceutical industry because it allows to predict all possible crystalline solid forms of small-molecule active ingredients. We have used a CSP-based cocrystal method rank ten potential coformers by energy cocrystallization reaction with antiviral drug candidate, MK-8876, and triol process intermediate, 2-ethynylglyclerol. For was performed retrospectively successfully predicted maleic acid as most likely be observed. The...
Self-assembled monolayers (SAMs) of rigid biphenyl thiols are employed as heterogeneous nucleants for the crystallization l-alanine and dl-valine. Powder X-ray diffraction interfacial angle measurements reveal that crystallographic planes corresponding to nucleation {200}, {020}, {011} on SAMs 4'-hydroxy-(4-mercaptobiphenyl), 4'-methyl-(4-mercaptobiphenyl), 4-(4-mercaptophenyl)pyridine gold (111) surfaces, respectively. In case dl-valine, monolayer surfaces act hydrogen bond acceptors (e.g.,...
Abstract The primary goal of crystallization process is to generate particles with controlled size, shape and solid form, the desired chemical purity. Many different types approaches including molecular level strategies have been devised employed control final structure crystals. One promising approach utilization self‐assembled monolayers (SAMs) as templates. Recently, we reported that single glycine crystals can nucleate on patterned metallic square islands, size morphology by dimensions...
A robust, green, and sustainable manufacturing process has been developed for the synthesis of gefapixant citrate, a P2X3 receptor antagonist that is under investigation treatment refractory unexplained chronic cough. The newly commercial features low mass intensity (PMI), short synthetic sequence, high overall yield, minimal environmental impact, significantly reduced API costs. key innovations are implementation highly efficient two-step methoxyphenol synthesis, an innovative pyrimidine in...
Herein we report the use of tetrakis (guanidinium) pyrenetetrasulfonate (G
Crystal polymorphism, characterized by different packing arrangements of the same compound, strongly ties to physical properties a molecule. Determining polymorphic landscape is complex and time-consuming, with number experimentally observed polymorphs varying widely from molecule Furthermore, disappearing polymorphs, phenomenon whereby forms cannot be reproduced, pose significant challenge for pharmaceutical industry. Herein, we focused on oxindole (OX), small rigid four known including...
Various synthetic routes to 2-isopropyl-4-methoxyphenol 3, the phenol core of Gefapixant citrate (MK-7264), are described, which provide better alternatives initial four-step supply route. These new include a coumarin fragmentation approach in flow, rhenium-catalyzed isopropylation mequinol, and bromination/methoxylation 2-isopropylphenol. After exploring several approaches, robust two-step process for preparation 3 from commodity starting material 2-isopropylphenol was developed. The...
Although the crystal structures of small-molecule compounds are often determined from single-crystal X-ray diffraction (scXRD), recent advances in three-dimensional electron (3DED) and structure prediction (CSP) methods promise to expand elucidation toolbox available crystallographer. Herein, a comparative assessment scXRD, 3DED, CSP combination with powder is carried out on two former drug candidate multicomponent key building block synthesis gefapixant citrate.
Abstract Single‐crystal X‐ray diffraction (SCXRD) is the preferred and most accurate technique for determining molecular structures. However, it can present challenges when dealing with specific small molecules active pharmaceutical ingredients (APIs), as many do not form quality crystals without coformers or be unstable. In this study, we introduce tetrakis(guanidinium) pyrenetetrasulfonate (G 4 PYR), a robust guanidinium‐organosulfonate (GS) framework that efficiently encapsulates APIs...
We describe the route development and multikilogram-scale synthesis of an HCV NS5B site D inhibitor, MK-8876. The key topics covered are (1) process improvement two main fragments; (2) optimization initially troublesome penultimate step, a bis(boronic acid) (BBA)-based borylation; (3) final Suzuki–Miyaura coupling; (4) control drug substance form. These efforts culminated in 28 kg delivery desired active pharmaceutical ingredient.