Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• The synthesis efforts discussed in this paper were critically enabled by the support of a diverse set of talented teams, functional leaders, and highly motivated scientists, without whom this work would not have been possible. We would like to thank Dr. Liliana Gallegos for help with quantum mechanics

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• -mannosidase II (LManII) and JBMan). Finally, structural and physicochemical properties of inhibitor:enzyme complexes were investigated at the theoretical level using molecular docking, hybrid quantum mechanics/molecular mechanics (QM/MM) calculations and fragmented molecular orbital pair interaction energy

• derivatives synthesized in this work, pair interaction energies between the bound inhibitors (29, 10, 20, 28, 30 and DIM) and amino acid residues of dGMII were calculated at the quantum mechanics level (FMO-PIEDA-MP2/6-31G*) in an active-site model of the inhibitor:enzyme complexes optimized at the hybrid QM

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• . We show that there is a great thermodynamic preference for hydropyrene and hydropyrenol formation, and hence most likely in the synthesis of the isoelisabethatriene products kinetic control is at play. Keywords: diterpenes; enzyme mechanism; quantum mechanics; terpene synthases; thermodynamic and

• inherent chemistry in these reactions and also points to some understanding of the possible thermodynamic and kinetic control in the enzyme. Results Reaction mechanism To better understand the HP and IE reaction pathways, we performed quantum mechanics (QM) calculations using density functional theory (DFT

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• ] describes this situation as using a so-called folk ontology (the everyday language of chemistry) as a fiction when discussing a very complex mathematical model (quantum mechanics). The third ontology, and the one that interests us most here, is how we describe molecules to computers for building databases

• net atomic charges) and of the bond. Physically, both result in the same change in dipole moment. Objectively, they are not distinguishable, as has been pointed out many times [33]. Quantum mechanics to Lewis or the reverse? The preceding section could easily be expanded into a complete book but

• reverse direction: Lewis structures are drawn or defined by a line notation such as SMILES, converted by one of several algorithms into a realistic 3D molecular structure and the resulting structure used as input for a quantum mechanical calculation. What quantum mechanics does far better than rationalize

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• complexes in C–H activation reactions. Along with the huge increase in computing power, this method becomes practically feasible to build model systems that provide parameters of the actual experimental systems with acceptable accuracy [16]. Recently, a predictive tool using quantum mechanics descriptors

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• cascade can provide important information towards a biosynthetic strategy for cyclooctatin and the biomanufacturing of related terpene structures. Keywords: active site; CotB2 cyclase; diterpene; mechanism; quantum mechanics; Introduction Enzymes catalyze numerous complex biochemical reactions in

• provide important information to derive a synthetic strategy for cyclooctatin and related terpene manufacturing. Future studies using hybrid quantum mechanics and molecular mechanics techniques to model the enzyme reaction in a complete enzyme environment will allow careful evaluation of the usefulness of

Water inside β-cyclodextrin cavity: amount, stability and mechanism of binding

• Stiliyana Pereva,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2019, 15, 1592–1600, doi:10.3762/bjoc.15.163

• details Different molecular modeling methods (quantum mechanics (QM), molecular dynamics (MD), docking and quantitative structure activity relationships (QSARs)) can be applied in studying the structure, dynamics, and energetics of the host CD systems. However, the results from different modeling (or

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• networks. Nonetheless, such systems remain an ensemble of smaller networks of molecules. Historically, our (dis)ability to comprehend the apparent complexity pushes science to develop theories to solve problems which were thought to be analytically unsolvable (e.g., classical or quantum mechanics) [100

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• a new generation of storage rings is under way [1]. In the quantum mechanics wave-particle duality, X-rays produced by a synchrotron can be regarded as a linearly polarized electromagnetic plane wave or as photons with energy given by Planck’s law. An X-ray photon that interacts with an atom can

Experimental and theoretical investigations into the stability of cyclic aminals

• Edgar Sawatzky,
• Antonios Drakopoulos,
• Martin Rölz,
• Christoph Sotriffer,
• Bernd Engels and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 2280–2292, doi:10.3762/bjoc.12.221

• of these valuable synthetic intermediates and natural products, appropriate conditions have to be chosen and for application as drug molecules their sensitivity towards hydrolysis has to be taken into account. Keywords: hydrolysis; kinetics; molecular mechanics; natural products; quantum mechanics

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• –Oppenheimer Molecular Dynamics (BOMD) calculations, so that nuclear motion and electronic structure are calculated separately, the former propagated classically and the latter determined using quantum mechanics. As with any computational (or experimental) study, there will always be a tradeoff between

Is organic chemistry science – and does this question make any sense at all?

• Andreas Kirschning and
• Thomas A. C. Reydon

Beilstein J. Org. Chem. 2015, 11, 893–896, doi:10.3762/bjoc.11.100

• of nature). In addition, an important consideration was that chemistry could perhaps be reduced to physics, and chemical phenomena could completely be described in terms of quantum mechanics. On such a view, chemistry would at best be a non-autonomous, applied science that depends for its explanatory

First principle investigation of the linker length effects on the thermodynamics of divalent pseudorotaxanes

• Andreas J. Achazi,
• Doreen Mollenhauer and
• Beate Paulus

Beilstein J. Org. Chem. 2015, 11, 687–692, doi:10.3762/bjoc.11.78

• . An explicit treatment of at least some solvent molecules would be desirable but is computationally not feasible at the required quantum mechanical level. A combined molecular mechanics/quantum mechanics treatment could be a solution to this problem in the future. Nevertheless, concerning the

Binding mode and free energy prediction of fisetin/β-cyclodextrin inclusion complexes

• Bodee Nutho,
• Wasinee Khuntawee,
• Chompoonut Rungnim,
• Piamsook Pongsawasdi,
• Peter Wolschann,
• Alfred Karpfen,
• Nawee Kungwan and
• Thanyada Rungrotmongkol

Beilstein J. Org. Chem. 2014, 10, 2789–2799, doi:10.3762/bjoc.10.296

• complexes. In addition, the quantum mechanics calculations with M06-2X/6-31G(d,p) clearly showed that both solvation effect and BSSE correction cannot be neglected for the energy determination of the chosen system. Keywords: cyclodextrin; fisetin; flavonoid; MM-PBSA; molecular dynamics simulation; QM-PBSA

• binding free energies were also corrected with quantum mechanics energy (∆EQM) by replacing the MM energy (∆EMM) in Equation 3 with density functional theory (DFT) calculation using the M06-2X functional with 6-31G(d,p) level of basis set. Besides, the full optimization in gas phase and PCM water model of

True and masked three-coordinate T-shaped platinum(II) intermediates

• Manuel A. Ortuño,
• Salvador Conejero and
• Agustí Lledós

Beilstein J. Org. Chem. 2013, 9, 1352–1382, doi:10.3762/bjoc.9.153

• water molecule. Indeed, quantum mechanics/molecular mechanics (QM/MM) calculations on the cisplatin–hen egg white lysozyme adduct confirmed the facile inclusion of a solvent water molecule in the first coordination shell of the platinum complex (Figure 13) [94]. NMR coupling constants to 195Pt as

The β-cyclodextrin/benzene complex and its hydrogen bonds – a theoretical study using molecular dynamics, quantum mechanics and COSMO-RS

• Jutta Erika Helga Köhler and
• Nicole Grczelschak-Mick

Beilstein J. Org. Chem. 2013, 9, 118–134, doi:10.3762/bjoc.9.15

• investigated by three different theoretical methods: classical quantum mechanics (QM) on AM1 and on the BP/TZVP-DISP3 level of approximation, and thirdly by classical molecular dynamics simulations (MD) at different temperatures (120 K and 273 to 300 K). The hydrogen bonds at the larger O2/O3 rim of empty β

• -empirical AM1, classical quantum mechanics [30] and COSMO-RS (Turbomole) [31], we observed that the orientation of all hydrogen bonds of the cyclodextrins already played a crucial role when the initial structures were constructed. It was not sufficient just to take the “normal route” of using the

• certainly no longer displayed the highly ordered hydrogen bonds of β-CD and benzene occupied many different positions inside the cavity, before it left the β-CD finally at its O2/O3 side. Keywords: AM1; benzene; COSMO-RS; cyclodextrin; hydrogen bonds; inclusion complex; molecular dynamics; quantum

Theoretical study on β-cyclodextrin inclusion complexes with propiconazole and protonated propiconazole

• Adrian Fifere,
• Narcisa Marangoci,
• Stelian Maier,
• Adina Coroaba,
• Dan Maftei and
• Mariana Pinteala

Beilstein J. Org. Chem. 2012, 8, 2191–2201, doi:10.3762/bjoc.8.247

• orientation of the guest molecules toward the β-CD cavity remains the same in the presence of water molecules. In this respect, the geometries of the complexes were optimized in aqua, by combining techniques of molecular mechanics and quantum mechanics [23]. The results given in Table 5 shows that, as solvent

• interconnection with α-(1,4)-glycosidic oxygen bridges. The resulting molecular geometries where fully optimized by AM1 and PM3 quantum-mechanics semi-empirical methods, under HyperChem software application. DFT single-point calculations were performed using GAUSSIAN 09 software package [25], at the level of

NMR studies of anion-induced conformational changes in diindolylureas and diindolylthioureas

• Damjan Makuc,
• Jennifer R. Hiscock,
• Mark E. Light,
• Philip A. Gale and
• Janez Plavec

Beilstein J. Org. Chem. 2011, 7, 1205–1214, doi:10.3762/bjoc.7.140

• complexes by quantum mechanics calculations The observations on the conformational equilibria in the absence and in the presence of anions were corroborated by quantum mechanical calculations at the B3LYP/6-311+G(d,p) level of theory by means of the Gaussian 03 [40] and Gaussian 09 [41] programs. Indole

• analysis was supported by quantum mechanics calculations and revealed that diindolylurea 1 exhibited conformational preorganization in DMSO-d6 solution. The anti–anti conformer, which could be stabilized by intramolecular hydrogen bonds between the C7β carbonyl group and indole NH proton, was predominant

• SO17 1BJ, United Kingdom Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 Ljubljana, Slovenia 10.3762/bjoc.7.140 Abstract The conformational properties of 1,3-diindolylureas and thioureas were studied by a combination of heteronuclear NMR spectroscopy and quantum