Probing machine learning models based on high throughput experimentation data for the discovery of asymmetric hydrogenation catalysts.

Enantioselective hydrogenation of olefins by Rh-based chiral catalysts has been extensively studied for more than 50 years. Naively, one would expect that everything about this transformation is known and that selecting a catalyst that induces the desired reactivity or selectivity is a trivial task. Nonetheless, ligand engineering or selection for any new prochiral olefin remains an empirical trial-error exercise.

Global reactivity models are impactful in industrial synthesis applications.

Artificial Intelligence is revolutionizing many aspects of the pharmaceutical industry. Deep learning models are now routinely applied to guide drug discovery projects leading to faster and improved findings, but there are still many tasks with enormous unrealized potential. One such task is the reaction yield prediction.

Bidirectional Graphormer for Reactivity Understanding: Neural Network Trained to Reaction Atom-to-Atom Mapping Task.

This work introduces , a new algorithm for reaction atom-to-atom mapping (AAM) based on a transformer neural network adopted for the direct processing of molecular graphs as sets of atoms and bonds, as opposed to SMILES/SELFIES sequence-based approaches, in combination with the Bidirectional Encoder Representations from Transformers (BERT) network. The graph transformer serves to extract molecular features that are tied to atoms and bonds. The BERT network is used for chemical transformation learning.

Improving Few- and Zero-Shot Reaction Template Prediction Using Modern Hopfield Networks.

Finding synthesis routes for molecules of interest is essential in the discovery of new drugs and materials. To find such routes, computer-assisted synthesis planning (CASP) methods are employed, which rely on a single-step model of chemical reactivity. In this study, we introduce a template-based single-step retrosynthesis model based on Modern Hopfield Networks, which learn an encoding of both molecules and reaction templates in order to predict the relevance of templates for a given molecule.

Atom-to-atom Mapping: A Benchmarking Study of Popular Mapping Algorithms and Consensus Strategies.

In this paper, we compare the most popular Atom-to-Atom Mapping (AAM) tools: ChemAxon, Indigo, RDTool, NameRXN (NextMove), and RXNMapper which implement different AAM algorithms. An open-source RDTool program was optimized, and its modified version ("new RDTool") was considered together with several consensus mapping strategies. The Condensed Graph of Reaction approach was used to calculate chemical distances and develop the "AAM fixer" algorithm for an automatized correction of erroneous mapping.

NMR study on the interaction of the conserved CREX 'stem-loop' in the Hepatitis E virus genome with a naphthyridine-based ligand.

A 2-amino-1,8-naphthyridine derivative that is described to bind single guanine bulges in RNA-DNA and RNA-RNA duplexes was synthesized and its interaction with the single G bulge in the conserved CREX of the Hepatitis E Virus (HEV) genome was explored by NMR and molecular modeling. Results indicate that the ligand intercalates in the internal loop, though none of the expected hydrogen bonds with the single G in the bulge could be demonstrated.

Contribution of dihydrouridine in folding of the D-arm in tRNA.

Posttranscriptional modifications of transfer RNAs (tRNAs) are proven to be critical for all core aspects of tRNA function. While the majority of tRNA modifications were discovered in the 1970s, their contribution in tRNA folding, stability, and decoding often remains elusive. In this work an NMR study was performed to obtain more insight in the role of the dihydrouridine (D) modification in the D-arm of tRNAi(Met) from S.

Synthesis and biological evaluation of 68Ga-bis-DOTA-PA as a potential agent for positron emission tomography imaging of necrosis.

Introduction: Necrosis is a form of cell death that occurs in a variety of pathological conditions but can also be the result of therapy in cancer treatment. A radiotracer that could image necrotic cell death using PET could therefore be a useful tool to provide relevant information on the disease activity or therapeutic efficacy and assist in diagnosis and therapy management of several disorders. Pamoic acid derivatives have previously been reported to show a selective uptake in tissue undergoing cellular death via necrosis.

Synthesis and biological evaluation of 68Ga labeled bis-DOTA-3,3'-(benzylidene)-bis-(1H-indole-2-carbohydrazide) as a PET tracer for in vivo visualization of necrosis.

The aim of the present study was to develop a (68)Ga labeled bis-DOTA derivative of benzylidene-bis-indole and compare the in vivo stability and biodistribution with that of the previously reported bis-DTPA derivate for in vivo imaging of necrosis using PET. Uptake of the tracer was evaluated in a mouse model of Fas-mediated hepatic apoptosis in correlation with histochemical stainings. The novel (68)Ga labeled tracer showed an improved in vivo stability and could therefore be used for selective non-invasive imaging of necrotic cell death using PET.

Sedoheptulose accumulation under CO₂ enrichment in leaves of Kalanchoë pinnata: a novel mechanism to enhance C and P homeostasis?

In contrast to the well-documented roles of its mono- and bisphosphate esters, the occurrence of free sedoheptulose in plant tissues remains a matter of conjecture. The present work sought to determine the origin of sedoheptulose formation in planta, as well as its physiological importance. Elevated CO2 and sucrose induction experiments were used to study sedoheptulose metabolism in the Crassulacean acid metabolism (CAM) plants Kalanchoë pinnata and Sedum spectabile.

Design of bioactive peptides from naturally occurring μ-conotoxin structures.

To date, cone snail toxins ("conotoxins") are of great interest in the pursuit of novel subtype-selective modulators of voltage-gated sodium channels (Na(v)s). Na(v)s participate in a wide range of electrophysiological processes. Consequently, their malfunctioning has been associated with numerous diseases.

Influence of the nucleobase and anchimeric assistance of the carboxyl acid groups in the hydrolysis of amino acid nucleoside phosphoramidates.

Nucleoside phosphoramidates (NPs) are a class of nucleotide analogues that has been developed as potential antiviral/antitumor prodrugs. Recently, we have shown that some amino acid nucleoside phosphoramidates (aaNPs) can act as substrates for viral polymerases like HIV-1 RT. Herein, we report the synthesis and hydrolysis of a series of new aaNPs, containing either natural or modified nucleobases to define the basis for their differential reactivity.

Pc16a, the first characterized peptide from Conus pictus venom, shows a novel disulfide connectivity.

A novel conotoxin, pc16a, was isolated from the venom of Conus pictus. This is the first peptide characterized from this South-African cone snail and it has only 11 amino acid residues, SCSCKRNFLCC*, with the rare cysteine framework XVI and a monoisotopic mass of 1257.6Da.

Reactivity of amino acid nucleoside phosphoramidates: a mechanistic quantum chemical study.

Recent experimental evidence (Maiti et al. Chem.-Eur.

Structure determination of the top-loop of the conserved 3'-terminal secondary structure in the genome of flaviviruses.

To what extent small differences in RNA sequences (mutations) can have a profound impact on biology remains an intriguing question. This effect can be studied by using untranslated RNA regions as a model. We have studied the influence of mutations on the structure of an RNA hairpin that occurs in the 3'-untranslated region (UTR) of Flaviviridae, and is known to have a large impact on the vector dependency of flaviviruses.

Metabolism of galactosyl-oligosaccharides in Stellaria media--discovery of stellariose synthase, a novel type of galactosyltransferase.

The raffinose family oligosaccharides (RFOs), including raffinose (Gal-alpha(1-->6)-Glc-alpha(1-->2)beta-Fru), stachyose (Gal-alpha(1-->6)-Gal-alpha(1-->6)-Glc-alpha(1-->2)beta-Fru) and higher degree of polymerization RFOs are the most widespread galactosyl-oligosaccharides (GOS) in the plant kingdom. Stellaria media is a typical representative of the Caryophyllaceae, a plant family lacking stachyose and the typical galactosyl extensions of stachyose. During cold treatment raffinose, lychnose (Gal-alpha(1-->6)-Glc-alpha(1-->2)beta-Fru-alpha(1-->1)-Gal) and stellariose (Gal-alpha(1-->6)-[Gal-alpha(1-->4)]-Glc-alpha(1-->2)beta-Fru-alpha(1-->1)-Gal) were found to accumulate in S.

Phosphodiester substrates for incorporation of nucleotides in DNA using HIV-1 reverse transcriptase.

In previous research we demonstrated that some amino acid derivatives of deoxyadenosine 5'-O-monophosphate act as substrates for incorporation into DNA by HIV-1 reverse transcriptase while retaining the canonical base-pair selectivity for all natural bases. Thus, some amino acids mimic the pyrophosphate group in the polymerization process with this enzyme. Herein we extended this study to the evaluation of a range of potential new leaving groups with aromatic and aliphatic structures carrying one or two carboxylic acid functions.

Isolation and characterization of a pentasaccharide from Stellaria media.

While classic raffinose family oligosaccharides (RFOs) such as raffinose and stachyose are common in plants, stachyose is absent in the Caryophyllaceae. Instead the tetrasaccharide lychnose α-d-Gal-(1→6)α-d-Glc-(1→2)β-d-Fru-(1→1)α-d-Gal can accumulate. Stellaria media, a representative member of this family, was used to isolate α-d-Gal-(1→6)-[α-d-Gal-(1→4)]α-d-Glc-(1→2)β-d-Fru-(1→1)α-d-Gal, a novel pentasaccharide with a lychnose backbone.

Synthesis and biological evaluation of an 123I-labeled bicyclic nucleoside analogue (BCNA) as potential SPECT tracer for VZV-tk reporter gene imaging.

An iodine-123 labeled bicyclic nucleoside analogue ([(123)I]-4) has been synthesized and evaluated as a potential single photon emission tomography (SPECT) reporter probe for the non-invasive imaging of expression of the varicella zoster virus thymidine kinase (VZV-tk) reporter gene. In vitro enzymatic assays revealed that the non-radioactive mono-iodo derivative 4 has good affinity for VZV-TK (IC(50): 4.2 microM).