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Self-assembly of modified amino acids facilitate the formation of various structures that have unique properties and therefore serve as excellent bio-organic scaffolds for diverse applications.

A series of group 1 hydrocarbon-soluble donor free aluminates [AM( tBuDHP)(TMP)Al( iBu) 2] (AM=Li, Na, K, Rb) have been synthesised by combining an alkali metal dihydropyridyl unit [(2- tBuC 5H 5N)AM)] containing a surrogate hydride (sp 3 C−H) with [( iBu) 2Al(TMP)]. These aluminates have been characterised by X-ray crystallography and NMR spectroscopy. While the lithium aluminate forms a monomer, the heavier alkali metal aluminates exist as polymeric chains propagated by non-covalent interactions between the alkali metal cations and the alkyldihydropyridyl units. Solvates [(THF)Li( tBuDHP)(TMP)Al( iBu) 2] and [(TMEDA)Na( tBuDHP)(TMP)Al( iBu) 2] have also been crystallographically characterised. Theoretical calculations show how the dispersion forces tend to increase on moving from Li to Rb, as opposed to the electrostatic forces of stabilization, which are orders of magnitude more significant. Having unique structural features, these bimetallic compounds can be considered as starting points for exploring unique reactivity trends as alkali-metal-aluminium hydride surrog[ATES].

pH dependence abounds in biochemical systems; however, many simulation methods used to investigate these systems do not consider this property. Using a modified version of the hybrid non-equilibrium molecular dynamics (MD)/Monte Carlo algorithm, we include a stochastic charge neutralization method, which is particularly suited to the MARTINI force field and enables artifact-free Ewald summation methods in electrostatic calculations. We demonstrate the efficacy of this method by reproducing pH-dependent self-assembly and self-organization behavior previously reported in experimental literature. In addition, we have carried out experimental oleic acid titrations where we report the results in a more relevant way for the comparison with computational methods than has previously been done.

SFX-MeOTAD [2,2′,7,7′-Tetrakis(N,N-di(4-methoxyphenyl)amino)-spiro-(fluorene-9,9′-xanthene)] (also known as X60) has emerged as a cost-effective alternative to the ubiquitous, but excessively-expensive, spiro-MeOTAD hole transport material (HTM) in perovskite solar cells. Using its pre-oxidised dicationic salt, SFX-(TFSI)2, a controlled concentration dependent conductivity tuning of this HTM without the requirement of air (oxygen) exposure is carried out. This study details the modifications in optical and electrical properties of this low cost HTM as a function of concentration of the dicationic salt (0-100 mol %) using UV-Vis absorption and electrical conductivity measurements. X-ray absorption and photoelectron spectroscopic investigations have been carried out to elucidate the role of the dicationic salt on the enhanced electronic properties of SFX-MeOTAD. By incorporating the dicationic SFX-(TFSI)2 it was shown that the conductivity of SFX-MeOTAD increased by 4 orders of magnitude from 2.55 × 10-8 S cm-1 to 9.4 × 10-4 S cm-1 using an optimal dopant concentration of 20.5 mol %. The degree of oxidation of SFX-MeOTAD was determined through UV-Vis absorption and consolidated by the computational calculations. XPS study reveal that doping SFX-MeOTAD with SFX(TFSI)2 results not only in oxidation of the HTM but also leads to variation in the local chemistry around carbon and nitrogen which directly influence the conductivity of the doped films. NEXAFS studies indicates that doping enhances the aromatic nature of the molecule initially but increasing the dopant concentration further affects the aromaticity and possibly the π stacking, similar to the trend seen in dopant concentration dependent conductivity of the SFX-MeOTAD films. These findings have implications on the choice of dopant concentration and counterions more generally for triarylamine based HTMs.

Herein we report the rational, computationally-guided design of an iridium(I) catalyst system capable of enabling directed hy-drogen isotope exchange (HIE) with the challenging sulfone directing group. Substrate binding energy was used as a parame-ter to guide rational ligand design via an in-silico catalyst screen, resulting in a lead series of chelated iridium(I) NHC-phosphine complexes. Subsequent preparative studies show that the optimal catalyst system displays high levels of activity in HIE, and we demonstrate the labeling of a broad scope of substituted aryl sulfones. We also show that the activity of the cata-lyst is maintained at low pressures of deuterium gas, and apply these conditions to tritium radiolabeling, including the expedi-ent synthesis of a tritium-labeled drug molecule.

The growth in information technology and computer capacity has opened up opportunities to deal with much and much larger data sets than even a decade ago. There has been a technological revolution of big data and Artificial Intelligence (AI). Perhaps many readers would immediately think about robotic surgery or self-driving cars, but there is much more to AI. This Short Communication starts with an overview of the key terms, including AI, machine learning, deep learning and Big Data. This Short Communication highlights so developments of AI in health that could benefit a low-income country like Nepal and stresses the need for Nepal’s health and education systems to track such developments and apply them locally. Moreover, Nepal needs to start growing its own AI expertise to help develop national or South Asian solutions. This would require investing in local resources such as access to computer power/capacity as well as training young Nepali to work in AI.

N-Arylindoles are transformed into dihydroacridines in a new type of rearrangement, through heating with triethylsilane and potassium tert-butoxide. Studies indicate that the pathway involves (i) the formation of indole radical anions followed by fragmentation of the indole C2–N bond, and (ii) a ring-closing reaction that follows a potassium-ion dependent hydrogen atom transfer step. Unexpected behaviors of ‘radical-trap’ substrates prove very helpful in framing the proposed mechanism., N-Arylindoles are transformed into dihydroacridines in a new type of rearrangement, through heating with triethylsilane and potassium tert-butoxide.

Unsaturated triacylglycerides are found in many commonly consumed foods, such as cooking oils, nuts and chocolate. There are however very few publications on Molecular Dynamics simulations of such molecules, and, to the best of our knowledge, no such published research on crystalline mono-unsaturated triacylglycerides. The work described in this paper is an evaluation of different force fields (GROMOS96 and NERD) to determine the best force field parameters to reproduce the crystalline and melted macroscopic properties of such molecules accurately. The best results were obtained by modifying the NERD force field, through which we were able to reproduce the crystalline and melted density as well as crystal dimensions of mono-unsaturated triacylglycerides.

We report on the supramolecular self-assembly of tripeptides and their

We report on the supramolecular self-assembly of tripeptides and their O-glycosylated analogues, in which the carbohydrate moiety is coupled to a central serine or threonine flanked by phenylalanine residues. The substitution of serine with threonine introduces differential side-chain interactions, which results in the formation of aggregates with different morphology. O-glycosylation decreases the aggregation propensity because of rebalancing of the Ï interactions. The glycopeptides form aggregates with reduced stiffness but increased thermal stability. Our results demonstrate that the designed minimalistic glycopeptides retain critical functional features of glycoproteins and therefore are promising tools for elucidation of molecular mechanisms involved in the glycoprotein interactome. They can also serve as an inspiration for the design of functional glycopeptide-based biomaterials., We acknowledge the EU’s H2020 program (Forecast 668983) and the Portuguese FCT (BD/113794/2015; PTDC/BTMMAT/ 28327/2017 CARDIOHEAL; M-ERA-NET2/0001/ 2016 INCIPIT) for the financial support. Part of this research was supported by National Science Foundation (NSF) grant CHE-1808143 and a grant of computer time from the City University of New York High Performance Computing Center under NSF grants CNS-0855217, CNS-0958379, and ACI- 1126113. D.D. thanks Maithreyi Ramakrishnan for provision of a dihedral analysis script and Mateusz Marianski for discussions.

Materials that combine the functionalities of both of proteins and graphene are of great interest for the engineering of biosensing, drug delivery, and regenerative devices. Graphene oxide (GO) offers an opportunity to design GO‐protein interactions but the need for harsh reduction processes to enable GO photoexcitation remains a limitation. A disinfector‐assisted low temperature method to reduce GO‐protein materials and fabricate surgical dressings with tuneable photothermal efficiency and bioactive properties for the postoperative treatment of melanoma is reported. The approach harnesses the capacity of 70% ethanol to penetrate the protein shell of microorganisms to infiltrate GO‐protein complexes and reduce GO at low temperature (85 °C) while maintaining the material structure and bioactivity. Both experiments and coarse‐grained simulations are used to describe the reduction process and assess the material properties. In vitro and in vivo validation revealed the capacity of the dressings to prevent tumor recurrence and promote healing after tumor resection.

Currently, there is a drive to develop the organoelement chemistry of sodium, the most abundant alkali metal on earth, as an alternative to that of rarer lithium, with the prime focus on sustainability. Organolithium compounds have been essential to the success of synthetic chemistry for more than a century, although their implementation has been essentially confined to stoichiometric synthesis. Here, we report on synthetic, structural, catalytic, mechanistic, and theoretical studies of a series of sodium diphenylphosphides, having unique structures defined by the Lewis base donor D solvating the Lewis acidic sodium cation. These donor complexes are explored as hydrophosphination catalysts on reacting Ph 2P–H with a range of alkynes and prove to be generally effective under ambient conditions, especially when n = 1 in [{Ph 2PNa(D) x} n]. Density functional theory (DFT) studies have shed light on the possible mechanisms of these catalytic cycles and how they relate to the E, Z, or α isomer formed.

Self-assembling peptide nanostructures have been shown to be of great importance in nature and have presented many promising applications, for example, in medicine as drug-delivery vehicles, biosensors, and antivirals. Being very promising candidates for the growing field of bottom-up manufacture of functional nanomaterials, previous work (Frederix, et al. 2011 and 2015) has screened all possible amino acid combinations for di- and tripeptides in search of such materials. However, the enormous complexity and variety of linear combinations of the 20 amino acids make exhaustive simulation of all combinations of tetrapeptides and above infeasible. Therefore, we have developed an active machine-learning method (also known as "iterative learning" and "evolutionary search method") which leverages a lower-resolution data set encompassing the whole search space and a just-in-time high-resolution data set which further analyzes those target peptides selected by the lower-resolution model. This model uses newly generated data upon each iteration to improve both lower- and higher-resolution models in the search for ideal candidates. Curation of the lower-resolution data set is explored as a method to control the selected candidates, based on criteria such as log P. A major aim of this method is to produce the best results in the least computationally demanding way. This model has been developed to be broadly applicable to other search spaces with minor changes to the algorithm, allowing its use in other areas of research.

Daniela Kroiss obtained her MSc degree in biotechnology at BOKU and is currently a PhD student in the biochemistry program at CUNY, where she works on a joint project between the Nanoscience Initiative and the University of Strathclyde. Gonen Ashkenasy is head of the Laboratory for Systems Chemistry at the Ben-Gurion University Chemistry Department. His research focuses on the design and analysis of synthetic replication networks. Adam Braunschweig earned his PhD in organic chemistry at the University of California and is an associate professor in the CUNY Nanoscience Initiative. His research focuses on the interface of organic chemistry with biology and material science. Tell Tuttle obtained his PhD in theoretical chemistry at Goteborg University and is a professor of theoretical chemistry at the University of Strathclyde. His research focuses on the directed discovery of peptide-based materials. Rein Ulijn gained his PhD in physical chemistry at the University of Strathclyde and is founding director of the Nanoscience Initiative at the CUNY Advanced Science Research Center. His research focuses on nanotechnology inspired by living systems.

Synthesized, isolated, and characterized by X‐ray crystallography and NMR spectroscopic studies, lithium phosphidoaluminate iBu3AlPPh2Li(THF)3 has been tested as a catalyst for hydrophosphination of alkynes, alkenes, and carbodiimides. Based on the collective evidence of stoichiometric reactions, NMR monitoring studies, kinetic analysis, and DFT calculations, a mechanism involving deprotonation, alkyne insertion, and protonolysis is proposed for the [iBu3AlHLi]2 aluminate catalyzed hydrophosphination of alkynes with diphenylphosphine. This study enhances further the development of transition‐metal‐free, atom‐economical homogeneous catalysis using common sustainable main‐group metals.

Remote directing groups in a bifunctional molecule do not always behave independently of one another in C–H activation chemistries. A combined DFT and experimental mechanistic study to provide enhanced Ir catalysts for chemoselective C–H deuteration of bifunctional aryl primary sulfonamides is described. This provides a pharmaceutically-relevant and limiting case study in using binding energies to predict intramolecular directing group chemoselectivity. Rational catalyst design, guided solely by qualitative substrate–catalyst binding free energy predictions, enabled intramolecular discrimination between competing ortho-directing groups in C–H activation and delivered improved catalysts for sulfonamide-selective C–H deuteration. As a result, chemoselective binding of the primary sulfonamide moiety was achieved in the face of an intrinsically more powerful pyrazole directing group present in the same molecule. Detailed DFT calculations and mechanistic experiments revealed a breakdown in the applied binding free energy model, illustrating the important interconnectivity of ligand design, substrate geometry, directing group cooperativity, and solvation in supporting DFT calculations. This work has important implications around attempts to predict intramolecular C–H activation directing group chemoselectivity using simplified monofunctional fragment molecules. More generally, these studies provide insights for catalyst design methods in late-stage C–H functionalisation., In C–H activation chemistries, the interpretation of the influence of remote directing groups in a bifunctional molecule depends on the in silico method used to inform catalyst design.

Dialkylaluminium amides iBu 2Al(TMP) and iBu 2Al(HMDS) can perform catalytic hydroboration of ketones with pinacolborane to form the expected boronic esters. However, repeating the same reactions stoichiometrically without a ketone leads unexpectedly to ring-opening of pinacolborane and insertion of its open chain into the Al−N(amido) bond. To date there has been limited knowledge on decomposition pathways of HBpin despite its prominent role in hydroboration chemistry. X-ray crystallography shows these mixed Al−B products [iBu 2Al{OC(Me) 2C(Me) 2O}B(H)(NR 2)] 2 (NR 2=TMP or HMDS) form dimers with an (AlO) 2 core and terminal B−N bonds. Since the bond retention (B−H) and bond breaking (B−O) in these transformations seemed surprising, DFT calculations run using M11/6-31G(d,p) gave an energy profile consistent with a σ-bond metathesis mechanism where London dispersion interactions between iBu and (amide) Me groups play an important stabilising role in the final outcome.

The text-book mechanism of bimolecular nucleophilic aromatic substitutions (SNAr) reactions is a stepwise process that proceeds via a so-called Meisenheimer intermediate. Only recently the alternative, concerted version of this mechanism has gained acceptance as more and more examples thereof have been reported. But so far only isolated examples of concerted SNAr reactions have been described and a coherent picture of when a SNAr reaction proceeds via a stepwise and when via a concerted mechanism has not yet been established. Here key factors are identified that influence the mechanistic choice of SNAr reactions. Moreover, the electron affinity is used as a simple descriptor to make a prediction on whether a given aryl fluoride substrate favors a concerted or stepwise mechanism.

The text-book mechanism of bimolecular nucleophilic aromatic substitutions (SNAr) reactions is a stepwise process that proceeds via a so-called Meisenheimer intermediate. Only recently the alternative, concerted version of this mechanism has gained acceptance as more and more examples thereof have been reported. But so far only isolated examples of concerted SNAr reactions have been described and a coherent picture of when a SNAr reaction proceeds via a stepwise and when via a concerted mechanism has not yet been established. Here key factors are identified that influence the mechanistic choice of SNAr reactions. Moreover, the electron affinity is used as a simple descriptor to make a prediction on whether a given aryl fluoride substrate favors a concerted or stepwise mechanism.

In biology, supramolecular recognition typically involves an 'induced‐fit' mechanism, where structures rearrange upon complexation to accommodate binding ligands. Designing minimalistic compounds with such adaptability is challenging as they involve subtle conformational changes that are energetically similar. Here, we demonstrate the integration of combinatorial screening with molecular modelling to identify heptapeptides that form a stable loop upon recognition of uridine triphosphate (UTP). Peptide sequences selected using phage display were refined computationally and correlated with experimental KD values. This combined approach may serve as a method for the de novo selection and subsequent rationalization of the compositional and organizational principles that dictate chemical functionality in flexible structures with dynamic conformations.

Melanin pigments have various properties that are of technological interest including photo- and radiation protection, rich coloration, and electronic functions. Nevertheless, laboratory-based synthesis of melanin and melanin-like materials with morphologies and chemical structures that are specifically optimized for these applications, is currently not possible. Here, melanin-like materials that are produced by enzymatic oxidation of a supramolecular tripeptide structures that are rich in tyrosine and have a 1D morphology are demonstrated, that are retained during the oxidation process while conducting tracks form through oxidative tyrosine crosslinking. Specifically, a minimalistic self-assembling peptide, Lys-Tyr-Tyr (KYY) with strong propensity to form supramolecular fibers, is utilized. Analysis by Raman spectroscopy shows that the tyrosines are pre-organized inside these fibers and, upon enzymatic oxidation, result in connected catechols. These form 1D conducting tracks along the length of the fiber, which gives rise to a level of internal disorder, but retention of the fiber morphology. This results in highly conductive structures demonstrated to be dominated by proton conduction. This work demonstrates the ability to control oxidation but retain a well-defined fibrous morphology that does not have a known equivalent in biology, and demonstrate exceptional conductivity that is enhanced by enzymatic oxidation.

In this work, we describe the development of a computational screening approach for tripeptide-dipeptide co-assembly. Studies are carried out both in water and in oil–water mixtures, to evaluate possible candidates that give rise to hydrogels or more stable emulsions, respectively, through nanofibre formation. The results give rise to design rules for the identification of promising systems for numerous types of soft materials. The possibility of achieving innovative functional materials through the co-assembly of tripeptides and dipeptides is studied. In particular, coarse-grained simulations allowed for the extraction of some promising dipeptides that, together with H-aspartyl-phenylalanyl-phenylalanine-OH (DFF), are able to act as hydrogelators or emulsifiers with superior characteristics relative to DFF on its own.

Silylation of primary and secondary amines is reported, using triethylsilane as the silylating reagent in the presence of potassium tert-butoxide (KOtBu). The reaction proceeds well in the presence of 0.2 equiv of KOtBu. In competition experiments, aniline is selectively silylated over aliphatic amines. Computational studies support a catalytic mechanism which is initiated by KOtBu interacting with the silane to form KH and silylated amine. The KH then takes over the role of base in the propagation of the cyclic mechanism, and deprotonates the amine. This reacts with R3SiH to afford the product R3SiNR’R” and regenerate KH.

Jüngste Entwicklungen in der experimentellen und theoretischen Chemie haben zur Identifizierung einer schnell wachsenden Klasse von nukleophilen aromatischen Substitutionsreaktionen geführt, die einem konzertierten Mechanismus (cSNAr) folgen, und nicht dem klassischen, zweistufigen SNAr-Mechanismus. Während klassische SNAr-Reaktionen auf die substantielle Aktivierung des aromatischen Ringes durch elektronenziehende Substituenten angewiesen sind, ist eine solche Aktivierung für den konzertierten Reaktionsverlauf nicht zwingend nötig.

Recent developments in experimental and computational chemistry have identified a rapidly growing class of nucleophilic aromatic substitutions that proceed by concerted (cSNAr) rather than classical, two‐step, SNAr mechanisms. Whereas traditional SNAr reactions require substantial activation of the aromatic ring by electron‐withdrawing substituents, such activating groups are not mandatory in the concerted pathways., Concerted or stepwise? A class of nucleophilic aromatic substitutions has been developed that proceeds by concerted (cSNAr) rather than classical, two‐step, SNAr mechanisms. Whereas traditional SNAr reactions require substantial activation of the aromatic ring by electron‐withdrawing substituents, such activating groups are not mandatory in the concerted pathways.

Rearrangements of o-tolyl aryl ethers, amines, and sulfides with the Grubbs–Stoltz reagent (Et3SiH + KOtBu) were recently announced, in which the ethers were converted to o-hydroxydiarylmethanes, while the (o-tol)(Ar)NH amines were transformed into dihydroacridines. Radical mechanisms were proposed, based on prior evidence for triethylsilyl radicals in this reagent system. A detailed computational investigation of the rearrangements of the aryl tolyl ethers now instead supports an anionic Truce–Smiles rearrangement, where the initial benzyl anion can be formed by either of two pathways: (i) direct deprotonation of the tolyl methyl group under basic conditions or (ii) electron transfer to an initially formed benzyl radical. By contrast, the rearrangements of o-tolyl aryl amines depend on the nature of the amine. Secondary amines undergo deprotonation of the N-H followed by a radical rearrangement, to form dihydroacridines, while tertiary amines form both dihydroacridines and diarylmethanes through radical and/or anionic pathways. Overall, this study highlights the competition between the reactive intermediates formed by the Et3SiH/KOtBu system.

Computational studies have been performed on potassium alkoxide-allenes, as well as potassium and lithium amido-allenes to probe the mechanism of their cyclizations to dihydrofurans and to 2,5-dihydropyrroles. A long-standing proposal envisaged electron transfer from dimsyl anions (formed by deprotonation of the solvent DMSO) but this pathway shows an exceptionally high kinetic barrier, while direct 5-endo-trig cyclization of the alkoxides and amides is much more easily achievable. The energy profiles for 4-exo-trig cyclizations onto the allenes are also explored, and the preferred formation of the observed five-membered products is rationalized.

Designing molecular disorder Melanins are a group of natural pigments that are the primary factor affecting skin color. Lampel et al. examined a family of melanin-inspired materials based on tripeptides containing tyrosine as precursors for polymeric pigments. They found that the supramolecular organization of the tripeptide assembly is the most important factor for the enzymatic oxidation, with the position of the tyrosine residue playing a dominant role. Thus, simply juggling the order of the peptides allowed tuning of the optical and electrical properties of the resulting polymers. Science , this issue p. 1064

We report on the biocatalytic activation of a self-assembling (unprotected) tripeptide to stabilize oil-in-water emulsions on-demand. This is achieved by the conversion of a phosphorylated precursor into a hydrogelator using alkaline phosphatase (AP) as the trigger. The rate of conversion, controlled by the amount of enzyme used, is shown to play a key role in dictating the morphology of the nanofibrous networks produced. When these amphiphilic tripeptides are used in biphasic mixtures, nanofibers are shown to self-assemble not only at the aqueous/organic interface but also throughout the surrounding buffer, thereby stabilizing the oil-in-water droplet dispersions. The use of enzymatic activation of tripeptide emulsions gives rise to enhanced control of the emulsification process because emulsions can be stabilized on-demand by simply adding AP. In addition, control over the emulsion stabilization can be achieved by taking advantage of the kinetics of dephosphorylation and consequent formation of different stabilizing nanofibrous networks at the interface and/or in the aqueous environment. This approach can be attractive for various cosmetic, food, or biomedical applications because both tunability of the tripeptide emulsion stability and on-demand stabilization of emulsions can be achieved.