Supramolecular materials: molecular packing of tetranitrotetrapropoxycalix[4]arene in highly stable films with second-order nonlinear optical properties

Highly stable films of tetranitrotetrapropoxycalix[4]arene (9) with second-order nonlinear optical (NLO) properties and a noncentrosymmetric structure were obtained by a novel crystallization process at 130-140 degrees C in a de electric field. The packing of 9 in these films was elucidated by a combination of X-ray diffraction, angle-dependent second- harmonic generation, and scanning force microscopy (SFM). The experimental results agree well with solid-state molecular dynamics calculations for these films. No crystalline phase was observed for nitrocalix[4]arene derivatives with longer or branched alkyl chains; this explains the limited NLO stability of films of these calixarenes. Scanning force microscopy o­n the aligned films of 9 showed two distinct surface lattice structures: a rectangular lattice (a = 9.3, b = 11.7 Angstrom) and a pseudohexagonal lattice (d approximate to 11.4 Angstrom). The combination of these data with the interlayer distance of 8.9 Angstrom (X-ray diffraction) allowed the packing of molecules of 9 in these structures to be fully elucidated at the molecular level

Rampant proteolysis at the intersection of therapy-induced hypoalbuminemia and acute pancreatitis

Protease inhibition is the intended mechanism of action for drugs across a broad range of diseases: cancer, cardiovascular and stroke, diabetes mellitus, macular degeneration and Alzheimer’s. Treatment for fungal and multiple viral infections, including Sars-Cov-2, also relies upon inhibition of pathogen-specific proteases. This work examines the non-therapeutic proteolytic activity of one such drug, nelfinavir (tradename VIRACEPT™), approved as an inhibitor of HIV protease, the largest, “biotech launch” in history at the time of its introduction. Methods are described in the companion manuscript [Leonard et al. (2022), 4open 5, 11]. These methods are not only suitable for examination of on-target activity but also of off-target activity. Herein, it is demonstrated that nelfinavir is active both as an inhibitor and as a promoter of proteolysis of key blood proteins. Observations are readily connected to known drug induction of acute pancreatitis and attendant hypoalbuminemia. The benefits of expanding molecular-level, early-stage, off-target/off-substrate activity drug candidate evaluation become apparent. Finally, the reality of drug-induced disease places new demands on existing clinical procedures, namely that side effects be approached as symptoms of an induced disease

Realtime, continuous assessment of complex-mixture protease and protease inhibitor activity

Recently the treatment PAXLOVID™ (nirmatrelvir co-packaged with ritonavir) was authorized for use as a treatment for COVID-19. The presumed mechanism of action of the treatment, an inhibitor of a Sars-Cov-2 “3CL” protease, continues decades-long interest in viral protease inhibition in the fight against pathogenic viruses (e.g., HIV protease inhibitors). Proteolysis assay methods vary widely, roughly bounded by interrogation of basic biochemistry and high-throughput, early-stage drug screening. Reported here are methods that provide unique and biologically relevant characterization of proteolysis and protease inhibition. A companion report provides evidence that these methods show promise for drug and basic biological discovery, especially for early detection of potential side effects. Electron spin resonance spectroscopy and spin labeling (ESRSL) of whole proteins are leveraged to monitor reactants and products of whole-protein digestion through differentiation of angular mobility of those products and reactants. These proof-of-concept data demonstrate consistency with prior art for all possible combinations of four proteases, two whole-protein substrates and three inhibitors. Thus, ESRSL is shown to uniquely and widely interrogate proteolysis of natural, whole-protein, substrates insuring the biological relevance of results

Carbon foam decorated with silver nanoparticles for electrochemical CO2 conversion

Electrochemistry is a promising method to recycle CO2 into useful carbon feedstock and for storing intermittent renewable energy. To date, Au and Ag nanoparticles are the most active catalysts for electrochemical conversion of CO2 to CO. However, agglomeration reduces the activity and the high cost slows widespread commercialization. Suitable support materials are thus needed to improve catalyst utilization. We explore carbon foam (CF) as a catalyst support. Compared with carbon black or graphene nanoplatelets, CF has higher surface area, larger pores, and more defects, resulting in improved uniformity of Ag nanoparticle distribution as well as higher activity and efficiency for CO2 conversion to CO

Scanning force microscopy studies on molecular packing and friction anisotropy in thin films of tetranitrotetrapropoxycalix[4]arene

Thin films of tetranitrotetrapropoxycalix[4]arene (1) show an unusual phase behavior and the formation of a complex multidomain structure. An endothermic phase transition, which occurs between 130 and 140 °C in bulk, was studied using differential scanning calorimetry, optical microscopy, magic angle solid-state NMR, and X-ray crystallography. In annealed films of 1, two types of crystalline domains (I and II) can be distinguished with different optical, morphological, and friction properties. These domains were investigated at the molecular level by a combination of multimode scanning force microscopy (SFM), optical microscopy, and X-ray diffraction experiments. SFM force measurements as well as tapping mode phase images showed that different functional groups are exposed at the surface for the different domains. The friction forces observed in SFM depend on the type of domain, the applied load, and the orientation of the domain with respect to the scanning direction. The friction forces observed at normal forces below ca. 240 nN are lower for type I domains than for type II domains. For forces higher than 260 nN an inversion of the relative friction is observed. Moreover, type I domains exhibit a friction anisotropy that can be attributed to different orientations of the molecular crystal structure with respect to the scanning direction. Two lattices were observed by high-resolution SFM in type I domains, one of rectangular symmetry (x = 10.0 Å, y = 11.8 Å, α = 90°) and one of pseudohexagonal symmetry (d = 11.6 Å), which were in agreement with the parameters of the (010) and (011) facets of the X-ray single-crystal structure (a = 23.94 Å, b = 33.01 Å, c = 20.59 Å, and α, ß, γ = 90°). In conclusion, the molecular packing and friction properties of the multidomain structure of thin films of 1 could be elucidated by SFM and complementary methods

Second-order nonlinear optical active calix[4]arene polyimides suitable for frequency doubling in the UV region

A new type of soluble calix[4]arene-based polyimides was prepared by reaction of bis(3-aminopropyl) dipropyl functionalized tetranitrocalix[4]arenes with hexafluoroisopropylidene diphthalic anhydride. Spin-coating of these polymers and subsequent electric field poling results in films that are highly transparent above 410 nm and exhibit high and thermally stable second harmonic generation coefficients. These properties make these materials very suitable Ear frequency-doubling applications in the UV region (820-410 nm)

A nitrogen-doped carbon catalyst for electrochemical CO2 conversion to CO with high selectivity and current density

We report characterization of a non-precious metal-free catalyst for the electrochemical reduction of CO2 to CO; namely, a pyrolyzed carbon nitride and multiwall carbon nanotube composite. This catalyst exhibits a high selectivity for production of CO over H2 (approximately 98 % CO and 2 % H2), as well as high activity in an electrochemical flow cell. The CO partial current density at intermediate cathode potentials (V=−1.46 V vs. Ag/AgCl) is up to 3.5× higher than state-of-the-art Ag nanoparticle-based catalysts, and the maximum current density is 90 mA cm−2. The mass activity and energy efficiency (up to 48 %) were also higher than the Ag nanoparticle reference. Moving away from precious metal catalysts without sacrificing activity or selectivity may significantly enhance the prospects of electrochemical CO2 reduction as an approach to reduce atmospheric CO2 emissions or as a method for load-leveling in relation to the use of intermittent renewable energy sources

A Nitrogen‐Doped Carbon Catalyst for Electrochemical CO 2

We report characterization of a non-precious metal-free catalyst for the electrochemical reduction of CO2 to CO; namely, a pyrolyzed carbon nitride and multiwall carbon nanotube composite. This catalyst exhibits a high selectivity for production of CO over H2 (approximately 98 % CO and 2 % H2), as well as high activity in an electrochemical flow cell. The CO partial current density at intermediate cathode potentials (V=−1.46 V vs. Ag/AgCl) is up to 3.5× higher than state-of-the-art Ag nanoparticle-based catalysts, and the maximum current density is 90 mA cm−2. The mass activity and energy efficiency (up to 48 %) were also higher than the Ag nanoparticle reference. Moving away from precious metal catalysts without sacrificing activity or selectivity may significantly enhance the prospects of electrochemical CO2 reduction as an approach to reduce atmospheric CO2 emissions or as a method for load-leveling in relation to the use of intermittent renewable energy sources