Machine‐Assisted Organic Synthesis

In this Review we describe how the advent of machines is impacting on organic synthesis programs, with particular emphasis on the practical issues associated with the design of chemical reactors. In the rapidly changing, multivariant environment of the research laboratory, equipment needs to be modular to accommodate high and low temperatures and pressures, enzymes, multiphase systems, slurries, gases, and organometallic compounds. Additional technologies have been developed to facilitate more specialized reaction techniques such as electrochemical and photochemical methods. All of these areas create both opportunities and challenges during adoption as enabling technologies.     

Enhancement of Photophysical and Photosensitizing Properties of Flavin Adenine Dinucleotide by Mutagenesis of the C‐Terminal Extension of a Bacterial Flavodoxin Reductase

The role of the mobile C‐terminal extension present in Rhodobacter capsulatus ferredoxin–NADP(H) reductase (RcFPR) was evaluated using steady‐state and dynamic spectroscopies for both intrinsic Trp and FAD in a series of mutants in the absence of NADP(H). Deletion of the six C‐terminal amino acids beyond Ala266 was combined with the replacement A266Y to emulate the structure of plastidic reductases. Our results show that these modifications of the wild‐type RcFPR produce subtle global conformational changes, but strongly reduce the local rigidity of the FAD‐binding pocket, exposing the isoalloxazine ring to the solvent. Thus, the ultrafast charge‐transfer quenching of ¹FAD* by the conserved Tyr66 residue was absent in the mutant series, producing enhancement of the excited singlet‐ and triplet‐state properties of FAD. This work highlights the delicate balance of the specific interactions between FAD and the surrounding amino acids, and how the functionality and/or photostability of redox flavoproteins can be modified.     

Differences in Dynamics between Crosslinked and Non‐Crosslinked Hyaluronates Measured by using Fast Field‐Cycling Relaxometry

The dynamic properties of water molecules in gels containing linear and crosslinked hyaluronic acid polymers are investigated by using an integrated approach that includes relaxometry, solid‐state NMR spectroscopy, and scanning electron microscopy. A model‐free analysis of field‐dependent nuclear relaxation is applied to obtain information on mobility and the population of different pools of water molecules in the gels. Differences between linear and crosslinked hyaluronic acid polymers are observed, indicating that crosslinking increases both the fraction and the correlation time of water molecules with slow dynamics.     

A noninvasive complementary study of an Egyptian polychrome cartonnage pigments using SEM,EPMA, and Raman spectroscopy

Raman spectroscopy, optical microscopy, scanning electron microscopy (SEM), and electron probe microanalysis (EPMA) were used to study pigments on an Egyptian cartonnage from the Ptolemaic period (305–30 bc ). The surface morphology of each color region was examined using backscattering (BS) and secondary electron imaging. SEM X-ray energy dispersive spectrometry and EPMA wavelength dispersive spectroscopy provided semiquantitative chemical analysis of each pigment. Raman spectroscopy was used to identify the minerals associated with the pigments. This technique confirmed the presence of cinnabar (α-HgS) in the red part of the fragments. A mixture of orpiment (As₂S₃) and bonazziite (β-As₄S₄) and/or alacránite (As₈S₉) was detected in the yellow regions of the fragments. The orange pigment was confirmed to be a mixture of orpiment, uzonite (χ-As₄S₅), and pararealgar (As₄S₄). Egyptian blue (CaCuSi₄O₁₀) and Egyptian green ((Cu,Ca)SiO₃) pigments were detected from blue/green dark-colored regions of the fragments.     

Controllability,uniqueness and existence of the incremental response: A mathematical criterion for elastoplastic constitutive laws

In this paper the onset of instabilities in elastoplastic materials is theoretically studied and a conceptual basis for understanding the physical implications of a loss of uniqueness and/or existence of the incremental response is provided. For this purpose, the concept of test controllability is reinterpreted and mixed stress–strain loading programmes are accounted for. A set of scalar indices, the moduli of instability, related with the inception of an unstable response is introduced and their dependency on the loading programme is explicitly illustrated. The paper shows that the use of these newly defined scalar measures provides support for an alternative definition for mechanical stability, which is closely related with the mathematical notions of existence and uniqueness of the predicted incremental response. In the final section, some mathematical properties of the moduli of instability are discussed, suggesting a novel reinterpretation of other well established theories and providing additional tools for the future application of the proposed framework.     

Risk processes with shot noise Cox claim number process and reserve dependent premium rate

We consider a suitable scaling, called the slow Markov walk limit, for a risk process with shot noise Cox claim number process and reserve dependent premium rate. We provide large deviation estimates for the ruin probability. Furthermore, we find an asymptotically efficient law for the simulation of the ruin probability using importance sampling. Finally, we present asymptotic bounds for ruin probabilities in the Bayesian setting.     

The Role of the Cricothyroid Joint Anatomy in Cricothyroid Approximation Surgery

Objectives/Hypothesis

Cricothyroid approximation (CTA) surgery aims at raising the voice pitch in male-to-female transsexuals. However, 30% of the patients are not satisfied with the result. The purpose of our study was to examine the cricothyroid joint (CTJ) biomechanics and to analyze if (and how) the CTJ anatomy influences the movement of the cricoid and, consequently, the elongation of the vocal fold and the voice pitch after CTA.

Methods

Twenty-four cadaver larynges were examined with high-resolution computerized tomography and MIMICS three-dimensional imaging software (Materialise Interactive Medical Image Control System, Leuven, Belgium). After superimposing the two scans taken in “neutral” and in “CTA” positions, vector geometrical analysis was used to determine the effective rotation axis of the CTJ and to calculate the elongation of the vocal folds after CTA.

Results

Our results showed that the cricoid rotates around an axis, the position of which depends on the anatomical structure of the CTJ. Based on the location of this effective rotation axis, we could distinguish three groups. In group I (N = 13), the rotation axis was located in the lower third; in group II (N = 5), it was located in the middle third; and in group III (N = 6), it was located in the upper third of the cricoid. The elongations of the vocal fold were 12%, 8%, and 3%, in groups I, II, and III, respectively.

Conclusions

The anatomical structure of the CTJ influences directly (1) the position of the effective rotation axis and (2) the elongation of the vocal folds.     

Assessing the optical changes in dissolved organic matter in humic lakes by spectral slope distributions

The impact of photodegradation and mixing processes on the optical properties of dissolved organic matter (DOM) was examined using a distribution of absorption spectral slopes and fluorescence measurements in two Argentine lakes. By examining the variability of the absorption spectral slopes throughout the ultraviolet and visible wavelengths, it was possible to determine which wavelength intervals were most sensitive to dominant loss processes. For DOM photodegradation, results show that increases in the absorption spectral slope between 265 and 305 nm were highly sensitive to increased exposure to solar ultraviolet radiation. A slightly larger wavelength range (265-340 nm) was found to be influenced when both mixing and photodegradation processes were considered, in terms DOM residence time, DOM absorption and UV diffuse attenuation coefficients. This same interval of spectral slopes (265-340 nm) was found to highly correlate with changes in fluorescence emission/excitation in wavelengths that are typically associated with terrestrial humic-like DOM. The identification of specific wavelength intervals, rather than the use of standard wavelength intervals or ratios, improved our ability to identify the dominant dissolved organic matter (humic-like) and major loss mechanisms (photodegradation) in these lakes.     

Shape memory epoxies based on networks with chemical and physical crosslinks

Epoxies are an important family of shape memory polymers (SMP) due to their excellent stability and thermo-mechanical endurance and the high values of shape fixity and shape recovery. Actuators based on these materials can be designed for large tensile elongations (e.g., 75% or higher) or large recovered stresses (e.g., 3 MPa or higher). However, meeting these requirements simultaneously is a difficult task because changes in the crosslink density affect both variables in opposite ways. We show that an SMP based on an epoxy network with both chemical and physical crosslinks could be strained up to 75% in four repeated shape memory cycles with tensile stresses close to 3 MPa. Shape fixity and shape recovery values were close to 98% and 96%, respectively, for everyone of the cycles, without any significant change between the first and subsequent cycles.     

Tetra-2,3-pyrazinoporphyrazines with externally appended thienyl rings: synthesis, UV-visible spectra, electrochemical behavior, and photoactivity for the generation of singlet oxygen

A series of pyrazinoporphyrazine macrocycles carrying externally appended 2-thienyl rings, represented as [Th(8)TPyzPzM], where Th(8)TPyzPz = tetrakis-2,3-[5,6-di(2-thienyl)pyrazino]porphyrazinato anion and M = Mg(II)(H(2)O), Zn(II), Co(II), Cu(II), or 2H(1), were prepared and isolated as solid air-stable hydrated species. All of the compounds, completely insoluble in water, were characterized by their UV-visible spectra and electrochemical behavior in solutions of dimethylformamide (DMF), dimethyl sulfoxide, and pyridine. Molecular aggregation occurs at concentrations of ca. 10(-4) M, but monomers are formed in more dilute solutions of 10(-5) M or less. The examined octathienyl compounds [Th(8)TPyzPzM] behave as electron-deficient macrocycles, and UV-visible spectral measurements provide useful information about how the peripheral thienyl rings influence the electronic distribution over the entire macrocyclic framework. Cyclic voltammetric and spectroelectrochemical data confirm the easier reducibility of the compounds as compared to the related phthalocyanine analogues, and the overall redox behavior and thermodynamic potentials for the four stepwise one-electron reductions of the compounds are similar to those of the earlier examined octapyridinated analogues [Py(8)TPyzPzM]. Quantum yields (Φ(Δ)) for the generation of singlet oxygen, (1)O(2), the cytotoxic agent active in photodynamic therapy (PDT), and fluorescence quantum yields (Φ(F)) were measured for the Zn(II) and Mg(II) complexes, [Th(8)TPyzPzZn] and [Th(8)TPyzPzMg(H(2)O)], and the data were compared to those of corresponding octapyridino macrocycles [Py(8)TPyzPzZn] and [Py(8)TPyzPzMg(H(2)O)] and their related octacations [(2-Mepy)(8)TPyzPzZn](8+) and [(2-Mepy)(8)TPyzPzMg(H(2)O)](8+). These measurements were carried out in DMF and in DMF preacidified with HCl (ca. 10(-4) M). All of the examined Zn(II) compounds behave as excellent photosensitizers (Φ(Δ) = 0.4-0.6) both in DMF and DMF/HCl solutions, whereas noticeable fluorescence activity (Φ(F) = 0.36-0.43) in DMF/HCl solutions is shown by the Mg(II) derivatives; these data might provide perspectives for applications in PDT (Zn(II)) and imaging response and diagnosis (Mg(II)).