Kinetic, isotopic, and infrared studies on well-defined dispersed Pt clusters are combined here with first-principle theoretical methods on model cluster surfaces to probe the mechanism and structural requirements for CO oxidation catalysis at conditions typical of its industrial practice. CO oxidation turnover rates and the dynamics and thermodynamics of adsorption-desorption processes on cluster surfaces saturated with chemisorbed CO were measured on 1-20 nm Pt clusters under conditions of strict kinetic control. Turnover rates are proportional to O(2) pressure and inversely proportional to CO pressure, consistent with kinetically relevant irreversible O(2) activation steps on vacant sites present within saturated CO monolayers. These conclusions are consistent with the lack of isotopic scrambling in C(16)O-(18)O(2)-(16)O(2) reactions, and with infrared bands for chemisorbed CO that did not change within a CO pressure range that strongly influenced CO oxidation turnover rates. Density functional theory estimates of rate and equilibrium constants show that the kinetically relevant O(2) activation steps involve direct O(2)* (or O(2)) reactions with CO* to form reactive O*-O-C*=O intermediates that decompose to form CO(2) and chemisorbed O*, instead of unassisted activation steps involving molecular adsorption and subsequent dissociation of O(2). These CO-assisted O(2) dissociation pathways avoid the higher barriers imposed by the spin-forbidden transitions required for unassisted O(2) dissociation on surfaces saturated with chemisorbed CO. Measured rate parameters for CO oxidation were independent of Pt cluster size; these parameters depend on the ratio of rate constants for O(2) reactions with CO* and CO adsorption equilibrium constants, which reflect the respective activation barriers and reaction enthalpies for these two steps. Infrared spectra during isotopic displacement and thermal desorption with (12)CO-(13)CO mixtures showed that the binding, dynamics, and thermodynamics of CO chemisorbed at saturation coverages do not depend on Pt cluster size in a range that strongly affects the coordination of Pt atoms exposed at cluster surfaces. These data and their theoretical and mechanistic interpretations indicate that the remarkable structure insensitivity observed for CO oxidation reactions reflects average CO binding properties that are essentially independent of cluster size. Theoretical estimates of rate and equilibrium constants for surface reactions and CO adsorption show that both parameters increase as the coordination of exposed Pt atoms decreases in Pt(201) cluster surfaces; such compensation dampens but does not eliminate coordination and cluster size effects on measured rate constants. The structural features and intrinsic non-uniformity of cluster surfaces weaken when CO forms saturated monolayers on such surfaces, apparently because surfaces and adsorbates restructure to balance CO surface binding and CO-CO interaction energies.

The acid-catalyzed formation of carbon-carbon bonds from C1 precursors via CO insertion into chemisorbed methyl groups occurs selectively within eight-membered ring (8-MR) zeolite channels. This elementary step controls catalytic carbonylation rates of dimethyl ether (DME) to methyl acetate. The number of O-H groups within 8-MR channels was measured by rigorous deconvolution of the infrared bands for O-H groups in cation-exchanged and acid forms of mordenite (M,H-MOR) and ferrierite (H-FER) after adsorption of basic probe molecules of varying size. DME carbonylation rates are proportional to the number of O-H groups within 8-MR channels. Na+ cations selectively replaced protons within 8-MR channels and led to a disproportionate decrease in carbonylation turnover rates (per total H+). These conclusions are consistent with the low or undetectable rates of carbonylation on zeolites without 8-MR channels (H-BEA, H-FAU, H-MFI). Such specificity of methyl reactivity upon confinement within small channels appears to be unprecedented in catalysis by microporous solids, which typically select reactions by size exclusion of bulkier transition states.

This manuscript provides the results of an in-depth survey assessment of the capabilities, experience, and perspectives on continuous processing in the pharmaceutical sector, with respondents from both pharmaceutical companies and Contract Manufacturing Organizations (CMOs). The survey includes staffing (personnel), chemistry, reaction platforms, postreaction processing, analytical, regulatory, and factors that influence the adoption of continuous manufacturing. The results of the survey demonstrate that the industry has been increasing, and will continue to increase, the portion of total manufacturing executed as continuous processes with a decrease in batch processing. In general, most of the experience with continuous processing on scale have been enabling reaction chemistry, while postprocessing and analytical remain in the very early stages of development and implementation.

Process safety groups in the pharmaceutical industry are important components of active pharmaceutical ingredient (API) development through its life cycle from discovery to commercial scale. The pharmaceutical process safety laboratory staff conduct a series of tests to identify chemically unstable reagents, intermediates and solvents, and mixtures to ensure that the proposed operating conditions provide a sufficient safety margin from the onset of undesired and potentially catastrophic thermal decomposition. Across several pharmaceutical companies, the methods used for these assessments and how results and conclusions are made are widespread (vide infra). A working group was created with members from several pharmaceutical companies within the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), with the goal of precompetitive collaboration and to understand each of the participating companies’ procedures and assessment regarding process safety. Each company was invited to provide input using a blind survey format. This was done in the interest of making this knowledge accessible for the participating companies and the wider community of other pharma and chemical companies and even academic institutions in the US and throughout the world. This article provides the results of this in-depth survey of the members of the IQ Consortium thermal hazard working group. General issues around different tools used to assess thermal hazard risk and questions regarding staffing and tech transfer of process safety data/information from development to manufacturing were addressed. A snapshot of how various assessment strategies are employed as a function of stage of development (early, mid, and late) is also presented.

In situ FTIR spectroscopy at 1 cm(-1) resolution was conducted on n-hexane solutions of the bridged [Rh4(CO)9(mu-CO)3] in the interval T= 268-288 K and P(T)= 0.1-7.0 MPa using either helium or carbon monoxide as dissolved gas. Analysis of the spectral data sets was conducted using band-target entropy minimization (BTEM), in order to recover the pure component spectra. A new spectral pattern was recovered with terminal vibrations at 2075, 2069.8, 2044.6 and 2042 cm(-1). The new spectrum is consistent with an all-terminal [Rh4(CO)12] species with a C(3v) anticubeoctahedron structure where 2 different [Rh(CO)3] moieties exist, although the presence of some Td structure can not be entirely excluded. The equilibrium between all-terminal [Rh4(CO)12] and the bridged [Rh(4)(CO)9(mu-CO)3] was determined in the presence of both helium and CO. The equilibrium constant K(eq)=[Rh4(CO)12]/[Rh4(CO)9(mu-CO)3] at 275 K was ca. 0.011 and the determined equilibrium parameters were Delta(r)G= 12.63 +/- 4.8 kJ mol(-1), Delta(r)H=-21.45 +/- 2.3 kJ mol(-1) and Delta(r)S=-114.3 +/- 8.35 J mol(-1) K(-1). The free energy indicates a very small difference between the bridged and terminal geometry, and the lower entropy is consistent with a higher symmetry. This finding helps to address a long-standing issue concerning the existence of various [M4(CO)12] symmetries. In a more general context, the present study illustrates the considerable utility of quantitative infrared spectroscopy (occurring on a fast vibrational timescale) combined with sophisticated deconvolution techniques in order to resolve systems which have been demonstrated to be fluxional on the NMR timescale.