Chemistry-based Approaches Research Articles

On the Theoretical Quantification of Radii of Atoms in Molecules.

Despite the fundamental importance of radii of atoms in molecules for numerous applications in physics and chemistry, comprehensive methods for their theoretical evaluation are still scarce. Here, we present quantum chemistry-based approaches for evaluation of radii of atoms in molecules and assess their robustness by studying the agreement of van der Waals and solvent-excluded surfaces constructed by them with reference molecular surfaces. By studying a large data set of 1235 molecules, it is shown that estimation of radii via effective and free atomic volumes can accurately take the dependence of atomic radii on the chemical environment into account.

Influence of Surface Chemistry on Metal Deposition Outcomes in Copper Selenide-Based Nanoheterostructure Synthesis.

The use of nanoparticle surface chemistry to direct metal deposition has been well-studied in the modification of metal nanoparticle substrates but is not yet well-established for metal chalcogenide particle substrates, although integration of these particles into nanoheterostructures is of high interest. In this report, we investigate the effect of Cu2-xSe surface chemistry on the morphology of metal deposition on these plasmonic semiconductor nanoparticles. Specifically, we functionalize Cu2-xSe nanoparticles with a suite of 12 different ligands and investigate how different aspects of the ligand structure do or do not impact the morphology and extent of subsequent metal deposition on the Cu2-xSe surface. Surprisingly, our results indicate that the morphology of the resulting metal deposits and the extent of metal deposition onto the existing Cu2-xSe particle substrate are indistinguishable for the majority of ligands tested. An exception to these findings is observed for particles functionalized by quaternary alkylammonium bromides, which exhibit statistically distinct metal deposition patterns compared to all other ligands tested. We hypothesize that this unique behavior is due to a cooperative binding mechanism of the quaternary alkylammonium bromides to the surface of copper selenide. Taken together, these results yield both new strategies for controlling postsynthetic modification of copper selenide nanoparticles and also reveal limitations of surface chemistry-based approaches for this system.

Antibacterial and Antibiofilm Activities from Extracts of Selected Cholistani Plants

The Cholistani plants are used as a vital source of medicines by local nomads for a long time. According to recent studies, many pharmacological studies like antibacterial, antiviral, antifungal, and antidiabetic were done, but very few chemistry-based approaches are available. The current study was designed to evaluate the antibacterial potentials of extracts of Cholistani plants. Aqueous, ethanol, and n-hexane extracts were prepared, and extraction was done based on polarity. All the extracts were evaluated for antibacterial activities through the disc diffusion method. The Minimum Inhibitory Concentration (MIC) of each positive extract was measured. The results indicated that the aqueous extract of these plants was more effective than others. The overall trend of antibacterial activity was as follows aqueous >n-hexane >ethanol extracts in terms of solvent. In terms of bacteria, almost all extracts were effective against Klebsiella pneumonia. The overall antibacterial trend was Klebsiella pneumonia>Proteus vulgaris>Staphylococcus aureus>Escherichia coli>Pseudomonas aeuriginosa. The results indicate that Cholistani plants are a rich source of antibacterial agent(s) and can be used in crude or purified form.

Enhancing the Performance of Analytical Methods to Combat Doping in Sport

Ion mobility–mass spectrometry (IM–MS) has become a cornerstone bioanalytical technique over the last two decades. Major advances have included new technology and software that enabled higher resolving power measurements; however, chemistry-based approaches, such as derivatization reactions, have also shown tremendous promise. This article demonstrates our work using IM–MS to detect anabolic steroids and describes how this technology could one day find its way into the anti-doping world.

Tethering Complex Proteins and Protein Complexes for Optical Tweezers Experiments.

Tethering proteins to force probes, typically micrometer-sized beads, is a prerequisite for dissecting their properties with optical tweezers. DNA handles serve as spacers between the tethered protein of interest and the bead surface. Attachment sites of the DNA handles to both the surface of beads and to the protein of interest must be mechanically stable for optical tweezers experiments. The most prominent method for attaching DNA handles to proteins utilizes thiol chemistry, linking modified DNA to engineered cysteines in the target protein. This method, although experimentally straightforward, is impractical for the large number of proteins that endogenously contain multiple or essential cysteines at undesired positions. Here, we describe two alternative approaches that take advantage of genetically encoded tag sequences in the target protein. The first method uses the enzymes Sfp and BirA, and the second uses the more recently described SpyTag-SpyCatcher system. We outline the process of generating the DNA handles themselves, as well as how to make the DNA-protein chimeras for carrying out optical tweezers experiments. These methods have robustly worked for several diverse and complex proteins, including ones that are difficult to produce or purify, and for protein-containing complexes such as the ribosome. They will be useful in cases where chemistry-based approaches are impractical or not feasible.

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REACTIONS Reactions ShareShare onFacebookTwitterWechatLinked InRedditEmail C&EN, 2021, 99 (36), p 3October 4, 2021Cite this:C&EN 99, 36, 3Letters to the editorDelta-8-THCThe recent C&EN cover article highlighted controversies surrounding a cannabidiol-derived ∆8-tetrahydrocannabinol (delta-8-THC) (Aug. 30, 2021, page 24). Unfortunately, it spoke mostly about concerns and anxieties rather than solutions to the problem and technology opportunities. Besides, the subject hasn’t been linked to the accurate history of the core chemistry. Consequently, a cannabidiol-derived delta-8-THC was introduced as merely a popular cannabinoid that results from some obscure chemical transformations that lurk in the underground labs.However, a facile isomerization of cannabidiol (CBD) to THC, catalyzed by acids and metal salts, had been discovered far earlier than in the 1960s and described in one of the seminal papers, published by the US pioneer of the cannabinoid research Roger Adams (Journal of the American Chemical Society, 1940). An interest in CBD-to-THC conversion remained dormant and purely academic for a long time. But it was destined to be reinvigorated, with CBD becoming in the last decade a major commercial cannabinoid. The decades of prohibition and barriers to conduct scientific research led to the current gaps in the existing legislation and also grew urban myths, some of which penetrated into the published piece. One of those concerns the exothermic nature of the catalytic CBD-to-THC conversion.The implication of olivetol as a common and major degradation product is an example of another unfounded claim. Certificates of analysis are now mandatory and include quantification of delta-8-THC and delta-9-THC, along with other cannabinoids and contaminants.We could not agree more that a full analysis of delta-8-THC-associated degradation products and the establishment of their safety are crucial. But this clarity is not far off. The general fundamentals of catalytic isomerization and cyclization processes are covered in chemistry textbooks. The scientific and business communities need only devote reasonable resources to address the information gap amplified in the article. It is no secret that cannabis business interests, not academic researchers, have continued to drive research into delta-8-THC’s safety .As THC explorations expand, cutting-edge cannabis companies will adopt emerging conversion methodologies, without toxic solvents and purification processes in place, to produce safe, fully characterized delta-8-THC and delta-9-THC from hemp-derived CBD. The economic and safety advantages inherent in these emerging technologies ensure their substitution for the current solution chemistry-based approaches, the shortcomings of which are presented as intractable and disqualifying. We hope coverage of this fundamental innovation, affecting what will eventually be a $200 billion global market, is worthy of a C&EN cover sooner rather than later.Alex Nivorozhkin (Boston), Jacob Weintraub (North Easton, Massachusetts), Charlie Sinn (San Diego) CorrectionSept. 27, 2021, page 10: The news story about novel phosphorus and nitrogen chemistry incorrectly says a prismatic P3N3compound survived about 10 µs. It survived at least that long.

Nanotargeting of Resistant Infections with a Special Emphasis on the Biofilm Landscape.

Bacterial resistance to antimicrobial compounds is a growing concern in medical and public health circles. Overcoming the adaptable and duplicative resistance mechanisms of bacteria requires chemistry-based approaches. Engineered nanoparticles (NPs) now offer unique advantages toward this effort. However, most in situ infections (in humans) occur as attached biofilms enveloped in a protective surrounding matrix of extracellular polymers, where survival of microbial cells is enhanced. This presents special considerations in the design and deployment of antimicrobials. Here, we review recent efforts to combat resistant bacterial strains using NPs and, then, explore how NP surfaces may be specifically engineered to enhance the potency and delivery of antimicrobial compounds. Special NP-engineering challenges in the design of NPs must be overcome to penetrate the inherent protective barriers of the biofilm and to successfully deliver antimicrobials to bacterial cells. Future challenges are discussed in the development of new antibiotics and their mechanisms of action and targeted delivery via NPs.

Hybridization-based design of novel anticholinesterase indanone-carbamates for Alzheimer's disease: Synthesis, biological evaluation, and docking studies.

Inspired by the structures of donepezil and rivastigmine, a novel series of indanone-carbamate hybrids was synthesized using the pharmacophore hybridization-based design strategy, and their biological activities toward acetylcholinesterase (AChE) and butyrylcholinesterase were evaluated. Among the synthesized compounds, 4d and 4b showed the highest AChE inhibitory activities with IC50 values in the micromolar range (compound 4d: IC50 = 3.04 μM; compound 4b: IC50 = 4.64 μM). Moreover, the results of the Aβ1-40 aggregation assay revealed that compound 4b is a potent Aβ1-40 aggregation inhibitor. The kinetics of AChE enzymatic activity in the presence of 4b was investigated, and the results were indicative of a reversible partial noncompetitive type of inhibition. A molecular docking study was conducted to determine the possible allosteric binding mode of 4b with the enzyme. The allosteric nature of AChE inhibition by these compounds provides the opportunity for the design of subtype-selective enzyme inhibitors. The presented indanone-carbamate scaffold can be structurally modified and optimized through medicinal chemistry-based approaches for designing novel multitargeted anti-Alzheimer agents.

Continuous flow asymmetric synthesis of chiral active pharmaceutical ingredients and their advanced intermediates.

Catalytic enantioselective transformations provide well-established and direct access to stereogenic synthons that are broadly distributed among active pharmaceutical ingredients (APIs). These reactions have been demonstrated to benefit considerably from the merits of continuous processing and microreactor technology. Over the past few years, continuous flow enantioselective catalysis has grown into a mature field and has found diverse applications in asymmetric synthesis of pharmaceutically active substances. The present review therefore surveys flow chemistry-based approaches for the synthesis of chiral APIs and their advanced stereogenic intermediates, covering the utilization of biocatalysis, organometallic catalysis and metal-free organocatalysis to introduce asymmetry in continuously operated systems. Single-step processes, interrupted multistep flow syntheses, combined batch/flow processes and uninterrupted one-flow syntheses are discussed herein.

Design, synthesis, and biological evaluation of novel indanone-based hybrids as multifunctional cholinesterase inhibitors for Alzheimer's disease

New compounds containing indanone and carbamate moieties were designed based on the hybrid pharmacophore approach. The designed compounds were synthesized and fully characterized by using different methods such as IR, Mass, 1H NMR, 13C NMR, and HPTLC. In vitro inhibitory activities of all synthesized compounds were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The compound 3-[(5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl) methyl] phenyl (4-methoxyphenyl) carbamate (4h) showed the best inhibitory activities with IC50 values of 1.20 and 0.30 μM against AChE and BChE, respectively. In addition, this compound showed a β-amyloid self-aggregation inhibitory effect (86.8%), stronger than that of donepezil (45.5%). Moreover, significant neuroprotective activity on PC12 cells against H2O2 induced cell death was demonstrated for compound 4h at 10 and 100 µM concentrations. Kinetic studies using the 4h confirmed a partial non-competitive mixed type of inhibition mechanism on both enzymes. Considering the suggested inhibition mechanism, molecular docking was used to predict the possible allosteric binding mode of 4h with both AChE and BChE enzymes. The presented indanone-carbamate scaffold can be structurally modified and optimized through medicinal chemistry-based approaches for designing novel multi-target anti-Alzheimer agents.

Signature Fragment Ions of Biotinylated Peptides.

The use of biotin or biotin-containing reagents is an essential component of many protein purification and labeling technologies. Owing to its small size and high affinity to the avidin family of proteins, biotin is a versatile molecular handle that permits both enrichment and purity that is not easily achieved by other reagents. Traditionally, the use of biotinylation to enrich for proteins has not required the detection of the site of biotinylation. However, newer technologies for discovery of protein-protein interactions, such as APEX and BioID, as well as some of the click chemistry-based labeling approaches have underscored the importance of determining the exact residue that is modified by biotin. Anti-biotin antibody-based enrichment of biotinylated peptides (e.g., BioSITe) coupled to LC-MS/MS permit large-scale detection and localization of sites of biotinylation. As with any chemical modification of peptides, understanding the fragmentation patterns that result from biotin modification is essential to improving its detection by LC-MS/MS. Tandem mass spectra of biotinylated peptides has not yet been studied systematically. Here, we describe the various signature fragment ions generated with collision-induced dissociation of biotinylated peptides. We focused on biotin adducts attached to peptides generated by BioID and APEX experiments, including biotin, isotopically heavy biotin, and biotin-XX-phenol, a nonpermeable variant of biotin-phenol. We also highlight how the detection of biotinylated peptides in high-throughput studies poses certain computational challenges for accurate quantitation which need to be addressed. Our findings about signature fragment ions of biotinylated peptides should be helpful in the confirmation of biotinylation sites.

Abstract NT-103: TARGETING OVARIAN TUMORS WITH OXPHOS INHIBITORS

Abstract Aerobic glycolysis is an important metabolic adaptation in tumors. However, there is mounting evidence that oxidative phosphorylation (OXPHOS) also contributes to metabolism in cancer cells. Therefore, agents targeting OXPHOS can serve as novel anticancer agents. We will present data on small molecule agents that inhibit the proliferation of ovarian and other cancer cells by inhibiting mitochondrial electron transport. We have focused our attention on citral, plumbagin, curcumin, cinnamaldehyde, piperlongumine, perillaldehyde, nonenal and other naturally occurring agents. All of these molecules share a common molecular epitope, the unsaturated carbonyl that participates in redox reactions. Cancer cells treated with these agents show a marked decrease in oxygen consumption rate and an increase in extracellular acidification. The redox ratio (NADH/FAD) and cellular ATP levels also decrease in response to these small molecule agents. In our search for additional and more potent OXPHOS inhibitors we have discovered that the FDA-approved anti-malarial drug atovaquone is an efficient inhibitor of electron transport in ovarian cancer cells. Chronic administration of atovaquone decreases the growth of ID8 tumors in C57BL/6 mice. Investigation in to the mechanism of action of the unsaturated carbonyl compounds indicates that their initial effect in cancer cells is the immediate and substantial rise in oxygen radicals as a result of OXPHOS inhibition. This increase in reactive oxygen causes extensive oxidative damage leading to DNA strand breaks. Subsequently, we have observed activation of p53-mediated apoptosis. These experiments are suggesting that inhibition of OXPHOS and the subsequent increase in intracellular oxygen radicals can result in the reactivation of the tumor suppressive responses of at least a subset of the p53 mutants. Additionally, our studies also indicate that the oxidative stress occurring as a result of OXPHOS inhibition directly leads to inhibition of ion transport through the Na+/K+-ATPase. As a result of this inhibition, cancer cells are unable to maintain a normal membrane potential. Studies are currently underway to determine if the inability to maintain membrane potential also contributes to apoptotic cancer cell death induced by these unsaturated carbonyl-containing compounds. Oxidative stress caused by these compounds leads to an increase in superoxide dismutase, catalase and glutathione synthesis via the activation of Nrf-2. Inhibition of Nrf-2 results in an increase in the potency of the unsaturated carbonyl compounds. We are therefore examining Nrf-2 increase as a form of chemoresistance mechanism that likely impinges on the anti-cancer activity of the unsaturated carbonyl compounds. These studies are allowing us to develop medicinal chemistry-based approaches to develop novel molecules with increased potency and targetability as OXPHOS inhibitors for the treatment of ovarian cancer. Citation Format: Arvinder Kapur, Amruta Nayak, Mildred Felder, Allegra Cappucini, Spencer Ericksen, Yousef Alharbi, Bikash Pattnaik, Lisa Barroilhet, and Manish S. Patankar. TARGETING OVARIAN TUMORS WITH OXPHOS INHIBITORS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-103.

Protein-mediated gelation and nano-scale assembly of unfunctionalized hyaluronic acid and chondroitin sulfate

Background: Hyaluronic acid (HA) is a major component of the extracellular matrix (ECM) in the central nervous system and the only purely supramolecular glycosaminoglycan. Much focus has been given to using this high molecular weight polysaccharide for tissue engineering applications. In most studies, HA is covalently functionalized with moieties that can facilitate network formation through physical self-assembly, or covalent crosslinking (e.g. photo-catalyzed) as the polysaccharide does not gel on its own. However, these crosslinks are not the driving force of HA self-assembly in biological tissues. Methods: Oscillatory rheology, dynamic light scattering, and scanning electron microscopy were used to study albumin/HA structures. Dynamic light scattering and transmission electron microscopy were used to study albumin/chondroitin sulfate (CS) structures. UV-vis spectroscopy was used to demonstrate the potential for using protein-crosslinked polymers as an ECM-mimetic model to study transport of hydrophilic small molecules. Results: We examine the intermolecular interactions of two major glycosaminoglycans found in the human brain, HA and the lower molecular weight CS, with the model protein albumin. We report the properties of the resulting micro- and nano-materials. Albumin/HA mixtures formed supramolecular gels, and albumin/CS mixtures formed micro- and nanoparticles. These systems are formed from unfunctionalized polysaccharides, which is an attractive and simpler method of forming HA hydrogels and CS nanoparticles than functional chemistry-based approaches such as chemically modifying the polymer backbones. We also summarize the concentrations of HA and CS found in various mammalian brains, which could potentially be useful for biomimetic scaffold development in tissue engineering. Conclusions: Simple preparation and combination of commercially available charged biomacromolecules rapidly result in interesting self-assembled materials with structures at the micron and nanometer length-scales. Such materials may have utility in serving as cost-effective and simple models of nervous system electrostatic interactions and as in vitro drug release and model system for ECM transport studies.

Small structural alterations greatly influence the membrane affinity of lipophilic ligands: Membrane interactions of bafilomycin A1 and its desmethyl derivative bearing 19F-labeling.

Molecular behavior under bilayer membrane environments is one of the important research topics concerning how organic molecules exert their biological activities when interacting with cellular membranes. However, chemistry-based approaches to this property have not been successful when compared with the structural biological strategy on ligand-receptor interactions. Here, we investigated the molecular behavior of the lipophilic ATPase inhibitor bafilomycin A1 and its derivatives under a lipid environment from a chemical point of view. Our results revealed significant differences in membrane affinity and dynamics among ligands having different inhibitory potencies, suggesting the specific contribution of ligand-membrane interactions to their biological activity.

Molecular dynamics and quantum chemistry-based approaches to identify isoform selective HDAC2 inhibitor – a novel target to prevent Alzheimer’s disease

Histone deacetylase 2 (HDAC2) is an emerging target of Alzheimer’s disease. Four featured pharmacophore model (ADRR) with one H-bond acceptor (A), one H-bond donor (D), and two aromatic rings (R) was generated using experimentally reported compounds, ((E-5[3-benzenesulfonamido) phenyl]-N-hydroxypent-2-en-4-ynamide)) and (N’-hydroxy-N-phenyloctanediamide) with IC50 values of 0.16 ± 0.11 nM and 62 ± 0.15 nM, respectively. Quantum Polarized Ligand Docking and Binding Free Energy calculation was performed for the top three identified leads RH01652, JFD02573, and HTS00800 from HitFinder database. RH01652 (methyl 2-[({5-[(benzoylamino) methyl]-2-thienyl} sulfonyl) amino]-3-(1H-indol-3-yl) propanoate) with docking score (−12.62 kcal/mol) and binding free energy (−75.27 kcal/mol), shows good binding affinity. RH01652 interacts with Gly154, His183, Glu208, and Phe210 with four H-bonds and stabilized by π–π interactions with His146, Tyr209, and Phe210. DFT studies at B3LYP level with 6-31G* basis set for the lead RH01652 reveals low band gap/ΔE (EHOMO–ELUMO) of −0.16 eV, which illustrates good reactivity of the lead. MD simulation studies (40 ns) was performed to confirm the stability of lead binding. Comparative molecular docking studies of the lead RH01652 with class I HDACs (HDAC1, HDAC2, HDAC3, and HDAC8) shows higher binding affinity towards HDAC2. Thus, lead RH01652 could serve as template to design novel and potent inhibitor of HDAC2.

Critical Assessment of Small Molecule Identification 2016: automated methods

BackgroundThe fourth round of the Critical Assessment of Small Molecule Identification (CASMI) Contest (www.casmi-contest.org) was held in 2016, with two new categories for automated methods. This article covers the 208 challenges in Categories 2 and 3, without and with metadata, from organization, participation, results and post-contest evaluation of CASMI 2016 through to perspectives for future contests and small molecule annotation/identification.ResultsThe Input Output Kernel Regression (CSI:IOKR) machine learning approach performed best in “Category 2: Best Automatic Structural Identification—In Silico Fragmentation Only”, won by Team Brouard with 41% challenge wins. The winner of “Category 3: Best Automatic Structural Identification—Full Information” was Team Kind (MS-FINDER), with 76% challenge wins. The best methods were able to achieve over 30% Top 1 ranks in Category 2, with all methods ranking the correct candidate in the Top 10 in around 50% of challenges. This success rate rose to 70% Top 1 ranks in Category 3, with candidates in the Top 10 in over 80% of the challenges. The machine learning and chemistry-based approaches are shown to perform in complementary ways.ConclusionsThe improvement in (semi-)automated fragmentation methods for small molecule identification has been substantial. The achieved high rates of correct candidates in the Top 1 and Top 10, despite large candidate numbers, open up great possibilities for high-throughput annotation of untargeted analysis for “known unknowns”. As more high quality training data becomes available, the improvements in machine learning methods will likely continue, but the alternative approaches still provide valuable complementary information. Improved integration of experimental context will also improve identification success further for “real life” annotations. The true “unknown unknowns” remain to be evaluated in future CASMI contests.Graphical abstract.

Comparing Chemistry and Census-Based Estimates of Net Ecosystem Calcification on a Rim Reef in Bermuda

Coral reef net ecosystem calcification (NEC) has decreased for many Caribbean reefs over recent decades primarily due to a combination of declining coral cover and changing benthic community composition. Chemistry-based approaches to calculate NEC utilize the drawdown of seawater total alkalinity (TA) combined with residence time to calculate an instantaneous measurement of NEC. Census-based approaches combine annual growth rates with benthic cover and reef structural complexity to estimate NEC occurring over annual timescales. Here, NEC was calculated for Hog Reef in Bermuda using both chemistry and census-based NEC techniques to compare the mass-balance generated by the two methods and identify the dominant biocalcifiers at Hog Reef. Our findings indicate close agreement between the annual 2011 census-based NEC 2.35±1.01 kg CaCO3•m-2•y-1 and the chemistry-based NEC 2.23±1.02 kg CaCO3•m-2•y-1 at Hog Reef. An additional record of Hog Reef TA data calculated from an autonomous CO2 mooring measuring pCO2 and modeled pHtotal every 3-hours highlights the dynamic temporal variability in coral reef NEC. This ability for chemistry-based NEC techniques to capture higher frequency variability in coral reef NEC allows the mechanisms driving NEC variability to be explored and tested. Just four coral species, Diploria labyrinthiformis, Pseudodiploria strigosa, Millepora alcicornis, and Orbicella franksi, were identified by the census-based NEC as contributing to 94±19% of the total calcium carbonate production at Hog Reef suggesting these species should be highlighted for conservation to preserve current calcium carbonate production rates at Hog Reef. As coral cover continues to decline globally, the agreement between these NEC estimates suggest that either method, but ideally both methods, may serve as a useful tool for coral reef managers and conservation scientists to monitor the maintenance of coral reef structure and ecosystem services.

Recent Progress in Treating Protein-Ligand Interactions with Quantum-Mechanical Methods.

We review the first successes and failures of a “new wave” of quantum chemistry-based approaches to the treatment of protein/ligand interactions. These approaches share the use of “enhanced”, dispersion (D), and/or hydrogen-bond (H) corrected density functional theory (DFT) or semi-empirical quantum mechanical (SQM) methods, in combination with ensemble weighting techniques of some form to capture entropic effects. Benchmark and model system calculations in comparison to high-level theoretical as well as experimental references have shown that both DFT-D (dispersion-corrected density functional theory) and SQM-DH (dispersion and hydrogen bond-corrected semi-empirical quantum mechanical) perform much more accurately than older DFT and SQM approaches and also standard docking methods. In addition, DFT-D might soon become and SQM-DH already is fast enough to compute a large number of binding modes of comparably large protein/ligand complexes, thus allowing for a more accurate assessment of entropic effects.

ChemInform Abstract: Flow Chemistry as a Versatile Tool for the Synthesis of Triazoles

AbstractReview: 130 refs.

Andreas Marx

Andreas Marx