CIME4R: Exploring iterative, AI-guided chemical reaction optimization campaigns in their parameter space.

Chemical reaction optimization (RO) is an iterative process that results in large, high-dimensional datasets. Current tools allow for only limited analysis and understanding of parameter spaces, making it hard for scientists to review or follow changes throughout the process. With the recent emergence of using artificial intelligence (AI) models to aid RO, another level of complexity has been added.

Open-Source Chromatographic Data Analysis for Reaction Optimization and Screening.

Automation and digitalization solutions in the field of small molecule synthesis face new challenges for chemical reaction analysis, especially in the field of high-performance liquid chromatography (HPLC). Chromatographic data remains locked in vendors' hardware and software components, limiting their potential in automated workflows and data science applications. In this work, we present an open-source Python project called MOCCA for the analysis of HPLC-DAD (photodiode array detector) raw data.

Classifying and Understanding the Reactivities of Mo-Based Alkyne Metathesis Catalysts from Mo NMR Chemical Shift Descriptors.

The most active alkyne metathesis catalysts rely on well-defined Mo alkylidynes, XMo≡CR (X = OR), in particular the recently developed canopy catalyst family bearing silanolate ligand sets. Recent efforts to understand catalyst reactivity patterns have shown that NMR chemical shifts are powerful descriptors, though previous studies have mostly focused on ligand-based NMR descriptors. Here, we show in the context of alkyne metathesis that Mo chemical shift tensors encode detailed information on the electronic structure of these catalysts.

Novel insights into pivotal risk factors for rectal carriage of extended-spectrum-β-lactamase-producing enterobacterales within the general population in Lower Saxony, Germany.

Aims: To estimate the prevalence of extended-spectrum-β-lactamase (ESBL)-producing enterobacterales (ESBL-E) carriage in the general population of Lower Saxony, Germany, and to identify risk factors for being colonized.

Methods And Results: Participants were recruited through local press and information events. Detection of ESBL-E by culture was conducted using ESBL-selective chromagar plates containing third-generation cephalosporins.

Canopy Catalysts for Alkyne Metathesis: Investigations into a Bimolecular Decomposition Pathway and the Stability of the Podand Cap.

Molybdenum alkylidyne complexes with a trisilanolate podand ligand framework ("canopy catalysts") are the arguably most selective catalysts for alkyne metathesis known to date. Among them, complex 1 a endowed with a fence of lateral methyl substituents on the silicon linkers is the most reactive, although fairly high loadings are required in certain applications. It is now shown that this catalyst decomposes readily via a bimolecular pathway that engages the Mo≡CR entities in a stoichiometric triple-bond metathesis event to furnish RC≡CR and the corresponding dinuclear complex, 8, with a Mo≡Mo core.

Productive Alkyne Metathesis with "Canopy Catalysts" Mandates Pseudorotation.

Molybdenum alkylidyne complexes of the "canopy catalyst" series define new standards in the field of alkyne metathesis. The tripodal ligand framework lowers the symmetry of the metallacyclobutadiene complex formed by [2 + 2] cycloaddition with the substrate and imposes constraints onto the productive [2 + 2] cycloreversion; pseudorotation corrects this handicap and makes catalytic turnover possible. A combined spectroscopic, crystallographic, and computational study provides insights into this unorthodox mechanism and uncovers the role that metallatetrahedrane complexes play in certain cases.

Isolation of a Homoleptic Non-oxo Mo(V) Alkoxide Complex: Synthesis, Structure, and Electronic Properties of Penta--Butoxymolybdenum.

Treatment of [MoCl(THF)] with MOBu (M = Na, Li) does not result in simple metathetic ligand exchange but entails disproportionation with formation of the well-known dinuclear complex [(BuO)Mo≡Mo(OBu)] and a new paramagnetic compound, [Mo(OBu)]. This particular five-coordinate species is the first monomeric, homoleptic, all-oxygen-ligated but non-oxo 4d Mo(V) complex known to date; as such, it proves that the dominance of the Mo═O group over (high-valent) molybdenum chemistry can be challenged. [Mo(OBu)] was characterized in detail by a combined experimental/computational approach using X-ray diffraction; UV/vis, MCD, IR, EPR, and NMR spectroscopy; and quantum chemistry.

W NMR Spectroscopy Guides the Search for Tungsten Alkylidyne Catalysts for Alkyne Metathesis.

Triarylsilanolates are privileged ancillary ligands for molybdenum alkylidyne catalysts for alkyne metathesis but lead to disappointing results and poor stability in the tungsten series. H, W heteronuclear multiple bond correlation spectroscopy, exploiting a favorable J-coupling between the W center and the peripheral protons on the alkylidyne cap, revealed that these ligands upregulate the Lewis acidity to an extent that the tungstenacyclobutadiene formed in the initial [2+2] cycloaddition step is over-stabilized and the catalytic turnover brought to a halt. Guided by the W NMR shifts as a proxy for the Lewis acidity of the central atom and by an accompanying chemical shift tensor analysis of the alkylidyne unit, the ligand design was revisited and a more strongly π-donating all-alkoxide ligand prepared.

"Canopy Catalysts" for Alkyne Metathesis: Molybdenum Alkylidyne Complexes with a Tripodal Ligand Framework.

A new family of structurally well-defined molybdenum alkylidyne catalysts for alkyne metathesis, which is distinguished by a tripodal trisilanolate ligand architecture, is presented. Complexes of type combine the virtues of previous generations of silanolate-based catalysts with a significantly improved functional group tolerance. They are easy to prepare on scale; the modularity of the ligand synthesis allows the steric and electronic properties to be fine-tuned and hence the application profile of the catalysts to be optimized.

Molybdenum Alkylidyne Complexes with Tripodal Silanolate Ligands: The Next Generation of Alkyne Metathesis Catalysts.

A new type of molybdenum alkylidyne catalysts for alkyne metathesis is described, which is distinguished by an unconventional podand topology. These structurally well-defined complexes are easy to make on scale and proved to be tolerant toward numerous functional groups; even certain protic substituents were found to be compatible. The new catalysts were characterized by X-ray crystallography and by spectroscopic means, including Mo NMR.

C-H Pyridonation of (Hetero-)Arenes by Pyridinium Radical Cations.

Pyridones are important heteroaromatic scaffolds found in natural products and pharmaceuticals and are, therefore, of major interest in organic synthetic chemistry. Here we report the first C-H pyridonation of unactivated (hetero-)arenes, providing a methodology to directly access N-aryl-2- and 4-pyridones. Generation of pyridinium radical cations through single-electron reduction allows for the synthesis of pyridones on structurally complex molecules.

Divergent Late-Stage (Hetero)aryl C-H Amination by the Pyridinium Radical Cation.

(Hetero)arylamines constitute some of the most prevalent functional molecules, especially as pharmaceuticals. However, structurally complex aromatics currently cannot be converted into arylamines, so instead, each product isomer must be assembled through a multistep synthesis from simpler building blocks. Herein, we describe a late-stage aryl C-H amination reaction for the synthesis of complex primary arylamines that other reactions cannot access directly.

Phonetics exercises using the Alvin experiment-control software.

Purpose: Exercises are described that were designed to provide practice in phonetic transcription for students taking an introductory phonetics course. The goal was to allow instructors to offload much of the drill that would otherwise need to be covered in class or handled with paper-and-pencil tasks using text rather than speech as input.

Method: The exercises were developed using Alvin, a general-purpose software package for experiment design and control.

Quantifying the cepstral peak prominence, a measure of dysphonia.

Objective: The purpose of this study is to establish normative values for the smoothed cepstral peak prominence (CPPS) and its sensitivity and specificity as a measure of dysphonia.

Study Design: Prospective cohort study.

Methods: Voice samples of running speech were obtained from 835 patients and 50 volunteers.

Electret microphones with stiff diaphragms.

Electret microphones with stiff plates instead of flexible diaphragms are described. The stiff plate and a backplate, separated by a soft cellular polymer spacer ring, yield a capacitance that is varied by the incoming sound wave; thus a voltage change in the plates is induced. Various such plate microphones were built and characterized.

Perception of sinewave vowels.

There is a significant body of research examining the intelligibility of sinusoidal replicas of natural speech. Discussion has followed about what the sinewave speech phenomenon might imply about the mechanisms underlying phonetic recognition. However, most of this work has been conducted using sentence material, making it unclear what the contributions are of listeners' use of linguistic constraints versus lower level phonetic mechanisms.

Electret accelerometers: physics and dynamic characterization.

Electret microphones are produced in numbers that significantly exceed those for all other microphone types. This is due to the fact that air-borne electret sensors are of simple and low-cost design but have very good acoustical properties. In contrast, most of the discrete structure-borne sound sensors (or accelerometers) are based on the piezoelectric effect.

The role of f (0) and formant frequencies in distinguishing the voices of men and women.

The purpose of the present study was to determine the contributions of fundamental frequency (f (0)) and formants in cuing the distinction between men's and women's voices. A source-filter synthesizer was used to create four versions of 25 sentences spoken by men: (1) unmodified synthesis, (2) f (0) only shifted up toward values typical of women, (3) formants only shifted up toward values typical of women, and (4) both f (0) and formants shifted up. Identical methods were used to generate four corresponding versions of 25 sentences spoken by women, but with downward shifts.

Speech perception based on spectral peaks versus spectral shape.

This study was designed to measure the relative contributions to speech intelligibility of spectral envelope peaks (including, but not limited to formants) versus the detailed shape of the spectral envelope. The problem was addressed by asking listeners to identify sentences and nonsense syllables that were generated by two structurally identical source-filter synthesizers, one of which constructs the filter function based on the detailed spectral envelope shape while the other constructs the filter function using a purposely coarse estimate that is based entirely on the distribution of peaks in the envelope. Viewed in the broadest terms the results showed that nearly as much speech information is conveyed by the peaks-only method as by the detail-preserving method.

Open source software for experiment design and control.

The purpose of this paper is to describe a software package that can be used for performing such routine tasks as controlling listening experiments (e.g., simple labeling, discrimination, sentence intelligibility, and magnitude estimation), recording responses and response latencies, analyzing and plotting the results of those experiments, displaying instructions, and making scripted audio-recordings.

Cepstral peak prominence: a more reliable measure of dysphonia.

Quantification of perceptual voice characteristics allows the assessment of voice changes. Acoustic measures of jitter, shimmer, and noise-to-harmonic ratio (NHR) are often unreliable. Measures of cepstral peak prominence (CPP) may be more reliable predictors of dysphonia.

A narrow band pattern-matching model of vowel perception.

The purpose of this paper is to propose and evaluate a new model of vowel perception which assumes that vowel identity is recognized by a template-matching process involving the comparison of narrow band input spectra with a set of smoothed spectral-shape templates that are learned through ordinary exposure to speech. In the present simulation of this process, the input spectra are computed over a sufficiently long window to resolve individual harmonics of voiced speech. Prior to template creation and pattern matching, the narrow band spectra are amplitude equalized by a spectrum-level normalization process, and the information-bearing spectral peaks are enhanced by a "flooring" procedure that zeroes out spectral values below a threshold function consisting of a center-weighted running average of spectral amplitudes.

Preservation of place and manner cues during simultaneous communication: a spectral moments perspective.

Unlabelled: Spectral moments, which describe the distribution of frequencies in a spectrum, were used to investigate the preservation of acoustic cues to intelligibility of speech produced during simultaneous communication (SC) in relation to acoustic cues produced when speaking alone. The spectral moment data obtained from speech alone (SA) were comparable to those spectral moment data reported by Jongman, Wayland, and Wong (2000) and Nittrouer (1995). The spectral moments obtained from speech produced during SC were statistically indistinguishable from those obtained during SA, indicating no measurable degradation of obstruent spectral acoustic cues during SC.

Speech synthesis using damped sinusoids.

A speech synthesizer was developed that operates by summing exponentially damped sinusoids at frequencies and amplitudes corresponding to peaks derived from the spectrum envelope of the speech signal. The spectrum analysis begins with the calculation of a smoothed Fourier spectrum. A masking threshold is then computed for each frame as the running average of spectral amplitudes over an 800-Hz window.

Effects of consonant environment on vowel formant patterns.

A significant body of evidence has accumulated indicating that vowel identification is influenced by spectral change patterns. For example, a large-scale study of vowel formant patterns showed substantial improvements in category separability when a pattern classifier was trained on multiple samples of the formant pattern rather than a single sample at steady state [J. Hillenbrand et al.