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Causal mechanistic reasoning is a thinking strategy that can help students explain complex phenomena using core ideas commonly emphasized in separate undergraduate courses, as it requires students to identify underlying entities, unpack their relevant properties and interactions, and link them to construct mechanistic explanations. As a crossdisciplinary group of biologists, chemists, and teacher educators, we designed a scaffolded set of tasks that require content knowledge from biology and chemistry to construct nested hierarchical mechanistic explanations that span three scales (molecular, macromolecular, and cellular). We examined student explanations across seven introductory and upper-level biology and chemistry courses to determine how the construction of mechanistic explanations varied across courses and the relationship between the construction of mechanistic explanations at different scales. We found non-, partial, and complete mechanistic explanations in all courses and at each scale. Complete mechanistic explanation construction was lowest in introductory chemistry, about the same across biology and organic chemistry, and highest in biochemistry. Across tasks, the construction of a mechanistic explanation at a smaller scale was associated with constructing a mechanistic explanation for larger scales; however, the use of molecular scale disciplinary resources was only associated with complete mechanistic explanations at the macromolecular, not cellular scale.

Since the first award in 1901, the Nobel Prize has come to signify the pinnacle of scientific achievement. In this Voices piece in the August special issue of Cell Chemical Biology entitled "Bridging chemistry and biology," we ask Nobel laureates to reflect on the impact the prize had on them. We learn how it affected their life or work, their outlook on science, the lessons learned, and their advice for the next generation of scientists., Competing Interests: Declaration of interests T.R.C. receives royalties from W.W. Norton & Co. for his book The Catalyst. R.J.L is a founder of Septerna and is a consultant and stockholder. R.J.L is a member of the Board of Directors of Lexicon and a stockholder., (Copyright © 2024. Published by Elsevier Ltd.)

The Royal Swedish Academy of Sciences awarded the 2017 Nobel Prize for Chemistry to Jacques Dubochet, Joachim Frank, and Richard Henderson for "developing cryoelectron microscopy for the high-resolution structure determination of biomolecules in solution." Achieving this goal, which required innovation, persistence, and uncommon physical insight, has broadened horizons for structural studies in molecular and cell biology., (Copyright © 2017 Elsevier Inc. All rights reserved.)

DNA-encoded chemical library technologies are increasingly being adopted in drug discovery for hit and lead generation. DNA-encoded chemistry enables the exploration of chemical spaces four to five orders of magnitude more deeply than is achievable by traditional high-throughput screening methods. Operation of this technology requires developing a range of capabilities including aqueous synthetic chemistry, building block acquisition, oligonucleotide conjugation, large-scale molecular biological transformations, selection methodologies, PCR, sequencing, sequence data analysis and the analysis of large chemistry spaces. This Review provides an overview of the development and applications of DNA-encoded chemistry, highlighting the challenges and future directions for the use of this technology.

Improvements needed for automated crystallography include crystal detection and crystal harvesting. A technique that uses acoustic droplet ejection to harvest crystals was previously reported. Here a method is described for using the same acoustic instrument to detect protein crystals and to monitor crystal growth. Acoustic pulses were used to monitor the progress of crystallization trials and to detect the presence and location of protein crystals. Crystals were detected, and crystallization was monitored in aqueous solutions and in lipidic cubic phase. Using a commercially available acoustic instrument, crystals measuring ~150 µm or larger were readily detected. Simple laboratory techniques were used to increase the sensitivity to 50 µm by suspending the crystals away from the plastic surface of the crystallization plate. This increased the sensitivity by separating the strong signal generated by the plate bottom that can mask the signal from small protein crystals. It is possible to further boost the acoustic reflection from small crystals by reducing the wavelength of the incident sound pulse, but our current instrumentation does not allow this option. In the future, commercially available sound-emitting transducers with a characteristic frequency near 300 MHz should detect and monitor the growth of individual 3 µm crystals., (© 2015 Society for Laboratory Automation and Screening.)

Materials chemistry has been fundamental to the enormous field that encompasses the delivery of molecules both to desired sites and/or at desired rates and durations. The field encompasses the delivery of molecules including fertilizers, pesticides, herbicides, food ingredients, fragrances and biopharmaceuticals. A personal perspective is provided on our early work in this field that has enabled the controlled release of ionic substances and macromolecules. Also discussed are new paradigms in creating biomaterials for human use, the non-invasive delivery of molecules through the skin and lungs, the development of intelligent delivery systems and extensions to nanomedicine. With the advent of potentially newer biopharmaceutics such as siRNA, mRNA and gene editing approaches and their use being limited by delivery, future research in this field may be more critical than ever before.

Computers have changed the way we do science. Surrounded by a sea of data and with phenomenal computing capacity, the methodology and approach to scientific problems is evolving into a partnership between experiment, theory and data analysis. Given the pace of change of the last twenty-five years, it seems folly to speculate on the future, but along with unpredictable leaps of progress there will be a continuous evolution of capability, which points to opportunities and improvements that will certainly appear as our discipline matures.

This account highlights some of our recent activities focused on developing microfluidic technologies for application in high-throughput and high-information content chemical and biological analysis. Specifically, we discuss the use of continuous and segmented flow microfluidics for artificial membrane formation, the analysis of single cells and organisms, nanomaterial synthesis and DNA amplification via the polymerase chain reaction. In addition, we report on recent developments in small-volume detection technology that allow access to the vast amounts of chemical and biological information afforded by microfluidic systems.

In recent years classifiers generated with kernel-based methods, such as support vector machines (SVM), Gaussian processes (GP), regularization networks (RN), and binary kernel discrimination (BKD) have been very popular in chemoinformatics data analysis. Aizerman et al. were the first to introduce the notion of employing kernel-based classifiers in the area of pattern recognition. Their original scheme, which they termed the potential function method (PFM), can basically be viewed as a kernel-based perceptron procedure and arguably subsumes the modern kernel-based algorithms. PFM can be computationally much cheaper than modern kernel-based classifiers; furthermore, PFM is far simpler conceptually and easier to implement than the SVM, GP, and RN algorithms. Unfortunately, unlike, e.g., SVM, GP, and RN, PFM is not endowed with both theoretical guarantees and practical strategies to safeguard it against generating overfitting classifiers. This is, in our opinion, the reason why this simple and elegant method has not been taken up in chemoinformatics. In this paper we empirically address this drawback: while maintaining its simplicity, we demonstrate that PFM combined with a simple regularization scheme may yield binary classifiers that can be, in practice, as efficient as classifiers obtained by employing state-of-the-art kernel-based methods. Using a realistic classification example, the augmented PFM was used to generate binary classifiers. Using a large chemical data set, the generalization ability of PFM classifiers were then compared with the prediction power of Laplacian-modified naive Bayesian (LmNB), Winnow (WN), and SVM classifiers.

Heparan sulfate is a sulfated glycan that exhibits essential physiological functions. Interrogation of the specificity of heparan sulfate-mediated activities demands a library of structurally defined oligosaccharides. Chemical synthesis of large heparan sulfate oligosaccharides remains challenging. We report the synthesis of oligosaccharides with different sulfation patterns and sizes from a disaccharide building block using glycosyltransferases, heparan sulfate C(5)-epimerase, and sulfotransferases. This method offers a generic approach to prepare heparan sulfate oligosaccharides possessing predictable structures.

Outside formal university chemistry classes in Scotland, which existed mainly to fulfil the requirements of medical courses, chemistry teaching was available from extramural lecturers. This form of teaching was often aimed at medical students, who could fulfil their graduation requirements if the lecturer had approved status. However, most of those attending would not have been seeking any formal qualification: there was a wave of enthusiasm among people from many walks of life about gaining chemical knowledge. Audiences included fashionable gentlefolk, manufacturers and industrialists, apprentice surgeons, mechanics, and artisans. Much of the teaching was at a highly proficient level, chemists of the stature of Thomas Thomson, Andrew Ure, Andrew Fyfe, Edward Turner, William Gregory, Thomas Graham, David Boswell Reid and George Wilson all offering classes. For several such teachers, it was the first step in a career that would later lead to significant academic or governmental appointments. In an Appendix, the article lists forty-eight chemists who have been identified as having taught extramurally between the later eighteenth and mid-nineteenth centuries.

Chemistry with its key targets of providing materials and processes for conversion of matter is at the center stage of the energy challenge. Most energy conversion systems work on (bio)chemical energy carriers and require for their use suitable process and material solutions. The enormous scale of their application demands optimization beyond the incremental improvement of empirical discoveries. Knowledge-based systematic approaches are mandatory to arrive at scalable and sustainable solutions. Chemistry for energy, "ENERCHEM" contributes in many ways already today to the use of fossil energy carriers. Optimization of these processes exemplified by catalysis for fuels and chemicals production or by solid-state lightning can contribute in the near future substantially to the dual challenge of energy use and climate protection being in fact two sides of the same challenge. The paper focuses on the even greater role that ENERCHEM will have to play in the era of renewable energy systems where the storage of solar energy in chemical carries and batteries is a key requirement. A multidisciplinary and diversified approach is suggested to arrive at a stable and sustainable system of energy conversion processes. The timescales for transformation of the present energy scenario will be decades and the resources will be of global economic dimensions. ENERCHEM will have to provide the reliable basis for such technologies based on deep functional understanding.

In this paper we present the development of methods using circular dichroism spectropolarimetry with a custom-designed cuvette to increase the signal-to-noise ratio for the measurement of the secondary structure of adsorbed proteins, thus providing enhanced sensitivity and reproducibility. These methods were then applied to investigate how surface chemistry and solution concentration influence both the amount of adsorbed proteins and their secondary structure. Human fibrinogen and albumin were adsorbed onto alkanethiol self-assembled monolayers (SAMs) on gold with CH3, OCH2-CF3, NH2, COOH, and OH terminal groups from both dilute (0.1 mg/mL) and moderately concentrated (1.0 mg/mL) solutions. An increase in surface hydrophobicity was found to cause an increase in both the amount of the protein adsorbed and the degree of structural change that was caused by the adsorption process, while an increase in solution concentration caused an increase in the amount of protein adsorbed but a decrease in the degree of conformational change, with these effects being more pronounced on the more hydrophobic surfaces. The combined use of these two parameters (i.e., surface chemistry and solution concentration) thus provides ameans of independently varying the degree of structural change following adsorption from the amount of adsorbed protein. Further studies are underway to examine which of these factors most strongly influences platelet response, with the overall goal of developing a better understanding of the fundamental factors governing the hemocompatibility of biomaterial surfaces.

A new approach to promoting and controlling polymer surface functionalization with acidic or basic polar functional groups is demonstrated and evaluated. Blended polymer films were annealed under pH-buffered conditions, and polar end-functional groups were found to promote surface segregation of the functional polymers. Surface segregation of carboxylic acid (COOH)-functionalized polystyrene increases dramatically with increasing pH from 1.9 to 9.4, whereas the opposite behavior is seen for amine (NH2)-functionalized polystyrene. Neutron reflectometry and nuclear reaction analysis were used to obtain surface excess values for the functional polymers. Subsequent SCFT analysis of the composition versus depth profiles indicates that the affinity of each functional group for the polymer surface changes by about 3k(B)T over this pH range.

A new thermocatalytic method to destroy chlorinated solvents has been developed in the laboratory and tested in a pilot field study. The method employs a conventional Pt/Rh catalyst on a ceramic honeycomb. Reactions proceed at moderate temperatures in the simultaneous presence of oxygen and a reductant (mixed redox conditions) to minimize catalyst deactivation. In the laboratory, stable operation with high conversions (above 90% at residence times shorter than 1 s) for perchloroethylene (PCE) is achieved using hydrogen as the reductant. A molar ratio of H(2)/O(2)= 2 yields maximum conversions; the temperature required to produce maximum conversions is sensitive to influent PCE concentration. When a homologous series of aliphatic alkanes is used to replace hydrogen as the reductant, the resultant mixed redox conditions also produce high PCE conversions. It appears that the dissociation energy of the C-H bond in the respective alkane molecule is a strong determinant of the activation energy, and therefore the reaction rate, for PCE conversion. This new method was employed in a pilot field study in Tucson, Arizona. The mixed redox system was operated semicontinuously for 240 days with no degradation of catalyst performance and complete destruction of PCE and trichloroethylene in a soil vapor extraction gas stream. Use of propane as the reductant significantly reduced operating costs. Mixed redox destruction of chlorinated solvents provides a potentially viable alternative to current soil and groundwater remediation technologies.

Studies to assess the risks of revealing chemical structures by sharing various chemical descriptor data are presented. Descriptors examined include "Lipinski-like" properties, 2D-BCUT descriptors, and a high-dimensional "fingerprint-like" descriptor (MACCs-vector). We demonstrate that unless sufficient precautions are taken, de novo design software such as EA-Inventor is able to derive a unique chemical structure or a set of closely related analogs from some commonly used descriptors. Based on the results of our studies, a set of guidelines or recommendations for safely sharing chemical information without revealing chemical structure is presented. A procedure for assessing the risk of revealing chemical structure when exchanging chemical descriptor information was also developed. The procedure is generic and can be applied to any chemical descriptor or combination of descriptors and to any set of structures to enable a decision about whether the exchange of information can be done without revealing the chemical structures.

The carbazole assay is commonly employed to quantify heparin and other uronic acid-containing polysaccharides. Heparin-derived standard curves are often employed to quantify solutions of various natural and unnatural heparin structures that have different levels of sulfate substitution, different levels of N-sulfo and N-acetyl groups, and other structural changes as a consequence of reducing molecular weight. Recent studies in our laboratory have focused on chemically modified heparin derivatives comprised of structurally diverse N-acyl moieties substituted into heparin in place of N-sulfo groups. We report here that although differing degrees of 2-N-sulfo-, 2-N-acetyl- or 2-amino-d-glucosamine residues within heparin do not affect signal intensity in the carbazole assay, replacing N-sulfo groups in heparin with structurally diverse N-acyl moieties affords products that display significant variation in the assay. The structure of different N-acyl groups, and to a lesser extent the degree of N-acylation by individual N-acyl groups, is shown to variably alter signal intensity in the carbazole assay even though content and structure of uronic acid residues is unaltered.

The reaction in water of M(II) [M = Ni or Mn] with 1,10-phenanthroline (phen) and sodium pyrophosphate (Na4P2O7) in a 2:4:1 stoichiometry resulted in the crystallization of dinuclear complexes featuring the heretofore rare bridging pyrophosphate. Single-crystal X-ray diffraction studies revealed the complexes to be {[(phen)2Ni]2(micro-P2O7)} . 27H2O (1) and {[(phen)2Mn]2(micro-P2O7)} . 13H2O (2) where the asymmetric M(phen)2 units are bridged by bis-bidentate pyrophosphate, each metal ion exhibiting a distorted octahedral geometry. The bridging pyrophosphate places adjacent metal centers at 5.031 A in 1 and 4.700 A in 2, and its conformation also gives rise to an intramolecular pi-pi interaction between two adjacent phen ligands. Intermolecular pi-pi interactions between phen ligands from adjacent dinuclear complexes create an ornate 3D network in 1, whereas a 2D sheet results in 2. The hydrophilic nature of the pyrophosphate ligand leads to heavy hydration with the potential solvent-accessible area for 1 and 2 accounting for 45.7% and 26.4% of their unit cell volumes, respectively. Variable-temperature magnetic susceptibility measurements on polycrystalline samples of 1 and 2 revealed net weak intramolecular antiferromagnetic coupling between metal centers in both compounds with J = -3.77 cm(-1) in 1 and J = -0.88 cm(-1) in 2, the Hamiltonian being defined as H = -JSA.SB. The ability of the bis-bidentate pyrophosphate to mediate magnetic interactions between divalent first row transition metal ions is discussed bearing in mind the number and nature of the interacting magnetic orbitals.

A new method to form colloidally stable oligosaccharide-grafted synthetic polymer particles has been developed. The oligosaccharides, of weight-average degree of polymerization approximately 38, were obtained by enzymatic debranching of amylopectin. Through the use of a cerium(IV)-based redox initiation process, oligosaccharide chains are grafted onto a synthetic polymer colloid comprising electrostatically stabilized poly(methyl methacrylate) or polystyrene latex particles swollen with methyl methacrylate monomer. Ce(IV) creates a radical species on these oligosaccharides, which then propagates, initially with aqueous-phase monomer, then with the methyl methacrylate monomer inside the particles. Ultracentrifugation, NMR, and total starch analyses together prove that the grafting process has occurred, with at least 7.7 wt % starch grafted and a grafting efficiency of 33%. The surfactant used in latex preparation was removed by dialysis, resulting in particles colloidally stabilized with only linear starch as a steric stabilizer. The debranched starch that comprises these oligosaccharides is found to be a remarkably effective colloidal stabilizer, albeit at low electrolyte concentration, stabilizing particles with very sparse surface coverage.

The 2006 Nobel Prize in Chemistry has been awarded to Roger Kornberg for elucidating the molecular basis of eukaryotic transcription. The prize caps a decades-long quest to unlock one of the central mysteries of molecular biology-how RNA transcripts are assembled.

Biodegradation half-lives are needed for many applications in chemical screening, but these data are not available for most chemicals. To address this, in phase one of this work we correlated the much more abundant ready and inherent biodegradation test data with measured half-lives for water and soil. In phase two, we explored the utility of the BIOWIN models (in EPI Suite) and molecular fragments for predicting half-lives. BIOWIN model output was correlated directly with measured half-lives, and new models were developed by re-regressing the BIOWIN fragments against the half-lives. All of these approaches gave the best results when used for binary (fast/slow) classification of half-lives, with accuracy generally in the 70-80% range. In the last phase, we used the collected half-life data to examine the default half-lives assigned by EPI Suite and the PBT Profiler for use as input to their level III multimedia models. It is concluded that estimated half-lives should not be used for purposes other than binning or prioritizing chemicals unless accuracy improves significantly.

The Schools Malaria Project (http://emalaria.soton.ac.uk/) brings together school students with university researchers in the hunt for a new antimalaria drug. The design challenge being offered to students is to use a distributed drug search and selection system to design potential antimalaria drugs. The system is accessed via a Web interface. This e-science project displays the results of the trials in an accessible manner, giving students an opportunity for discussion and debate both with peers and with the university contacts. The project has been implemented by using distributed computing techniques, spreading computer load over a network of machines that cross institutional boundaries, forming a grid. This provides access to greater computing power and allows a much more complex and detailed formulation of the drug design problem to be tackled for research, teaching, and learning.

Chemical exposures in a university teaching lab were assessed using a tiered approach to modeling. Zero ventilation and well mixed room models estimated air concentrations of ethyl ether, n-hexane, and methylene chloride during distillation and extraction exercises. A simple, zero ventilation model determined that health risks from the ethyl ether exercise were minimum. N-hexane and methylene chloride exposures were evaluated with higher tiered, well mixed room models. An assumption that all of the solvent evaporated during the lab resulted in estimated n-hexane concentrations well below the occupational exposure limit. Methylene chloride concentration estimates using this approach were only one-half the occupational exposure limit, so the model was refined using information on the actual amount of solvent that evaporated. This resulted in a concentration estimate approximately one-fifth of the occupational exposure limit. Air sampling was done to evaluate model performance. Measured concentrations were higher than modeled concentrations by up to a factor of two but were still below applicable occupational exposure limits. The exposure models selected were deemed useful in the assessment of exposure acceptability in these labs.

Prototype processes were developed for the substantial suppression of acrylamide formation (40-95% compared to untreated controls) in cut surface fried potato products using potato chips (crisps) as the primary model. The most efficacious procedures employed sequentially both surface preparation and subsequent acrylamide precursor complexation and/or competitive inhibition processing steps. Surface preparation processing involved either various low-temperature (50-75 degrees C) aqueous (5-30 min) or ca. 80% ethanol blanch solutions for various times (1-5 min) combined with aqueous leaching steps (1-10 min) to reduce concentration of acrylamide precursors in the critical frying zone of cut potato surfaces. Acrylamide precursor complexation and/or competitive inhibition processing strategies included immersion exposure of prepared cut potato surfaces to solutions or dispersions of various combinations of either calcium chloride, phytic acid, chitosan, sodium acid pyrophosphate, or N-acetylcysteine.