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Quantum Chemical Calculation of Chemical Shifts in the Stereochemical Determination of Organic Compounds: A Practical Approach

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Handbook of Marine Natural Products

Abstract

In this chapter, we report an integrated approach of NMR and quantum mechanical calculation for the determination of the relative configuration of natural products. The entire protocol is described starting from building the investigated compound to the calculation of NMR properties at quantum theory level and the interpretation of the results. Each step of the protocol is described, and the main applied methods are reported. We report, as case studies, the determination of the relative configuration of two natural products: bonannione B isolated from Bonannia graeca, and callipeltin A isolated from the sponges Callipelta sp. and Latrunculia sp. Through the analysis of these natural products, we show the use of 13C chemical shift and homo and hetero J coupling constants, respectively, as an important tool in the interpretation of the experimental data for the determination of the relative configuration of organic compounds.

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References

  1. DiMicco S, Chini MG, Riccio R, Bifulco G (2010) Quantum mechanical calculation of NMR parameters in the stereostructural determination of natural products. Eur J Org Chem 8:1411–1434. doi:10.1002/ejoc.200901255

    Article  Google Scholar 

  2. Bifulco G, Dambruoso P, Gomez-Paloma L, Riccio R (2007) Determination of relative configuration in organic compounds by NMR spectroscopy and computational methods. Chem Rev 107:3744–3779. doi:10.1021/cr030733c

    Article  PubMed  CAS  Google Scholar 

  3. Barone G, Gomez-Paloma L, Duca D, Silvestri A, Riccio R, Bifulco G (2002) Structure validation of natural products by quantum-mechanical GIAO calculations of 13C NMR chemical shifts. Chem Eur J 8:3233–3239. doi:10.1002/1521-3765(20020715)8:14 < 3233::AID-CHEM3233 > 3.0.CO;2-0/abstract/

    Article  PubMed  CAS  Google Scholar 

  4. Barone G, Duca D, Silvestri A, Gomez-Paloma L, Riccio R, Bifulco G (2002) Determination of the relative stereochemistry of flexible organic compounds by ab initio methods: conformational analysis and Boltzmann-averaged GIAO 13C NMR chemical shifts. Chem Eur J 8:3240–3245. doi:10.1002/1521-3765(20020715)8:14 < 3240::AID-CHEM3240 > 3.0.CO;2-G/abstract

    Article  PubMed  CAS  Google Scholar 

  5. van Gunsteren WF, Berendsen HJC (1990) Computer simulation of molecular dynamics: methodology, applications, and perspectives in chemistry. Angew Chem Int Ed 29:992–1023. doi:10.1002/anie.199009921

    Article  Google Scholar 

  6. Höltje HD, Sippl W, Folkers G (2003) Molecular modeling basic principles and applications. Wiley-VCH, Weinheim

    Google Scholar 

  7. Chang G, Guida WC, Still WC (1989) An internal-coordinate Monte Carlo method for searching conformational space. J Am Chem Soc 111:4379–4386. doi:10.1021/ja00194a035

    Article  CAS  Google Scholar 

  8. Dewar MJS, Zoebisch EG, Healy EF, Stewart JJP (1985) Development and use of quantum mechanical molecular models. 76. AM1: a new general purpose quantum mechanical molecular model. J Am Chem Soc 107:3902–3909. doi:10.1021/ja00299a024

    Article  CAS  Google Scholar 

  9. Stewart JJP (1989) Optimization of parameters for semiempirical methods I. Method. J Comput Chem 10:209–220. doi:10.1002/jcc.540100208

    Article  CAS  Google Scholar 

  10. Rosselli S, Bruno M, Maggio A, Bellone G, Formisano C, Mattia CA, Di Micco S, Bifulco G (2007) Two new Flavonoids from Bonannia graeca: a DFT-NMR combined approach in solving structures. Eur J Org Chem 15:2504–2510. doi:10.1002/ejoc.200600969

    Article  Google Scholar 

  11. Dale JA, Mosher HS (1973) Nuclear magnetic resonance enantiomer regents. Configurational correlations via nuclear magnetic resonance chemical shifts of diastereomeric mandelate, O-methylmandelate, and.alpha.-methoxy-.alpha.-trifluoromethylphenylacetate (MTPA) esters. J Am Chem Soc 95:512–519. doi:10.1021/ja00783a034

    Article  CAS  Google Scholar 

  12. (a) Protein Data Bank (PDB) See http://www.rcsb.org/pdb/home/home.do; (b) Nucleic Acid Databank (NDB) See http://ndbserver.rutgers.edu/; (c) Cambridge Structural Database (CSD) See http://www.ccdc.cam.ac.uk/products/csd/; (d) Crystallography Open Database (COD) See http://www.crystallography.net/. Accessed 04 Nov 2011

  13. http://www.acdlabs.com/products/draw_nom/draw/chemsketch/. Accessed 04 Nov 2011

  14. MDL Information Systems, Inc. (MDL ISIS™) http://mdl-isis-draw.software.informer.com/. Accessed 04 Nov 2011

  15. http://www.cambridgesoft.com/software/ChemDraw/. Accessed 04 Nov 2011

  16. Discover molecular modeling software (1993) Biosym Technologies Inc., San Diego, CA

    Google Scholar 

  17. Insight INSIGHT II molecular modeling package (2000) Accelrys, San Diego, CA

    Google Scholar 

  18. http://accelrys.com/. Accessed 04 Nov 2011

  19. Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC (2005) GROMACS: fast, flexible, and free. J Comput Chem 26:1701–1718. doi:10.1002/jcc.20291

    Article  Google Scholar 

  20. http://www.gromacs.org/. Accessed 04 Nov 2011

  21. Wavefunction, Inc., Irvine. http://www.wavefun.com/products/spartan.html. Accessed 04 Nov 2011

  22. Mohamadi F, Richard NGJ, Guida WC, Liskamp R, Lipton M, Caufield C, Chang G, Hendrickson T, Still WC (1990) MacroModel – an integrated software system for modeling organic and bioorganic molecules using molecular mechanics. J Comput Chem 11:440–467. doi:10.1002/jcc.540110405

    Article  CAS  Google Scholar 

  23. Allinger NL (1977) Conformational analysis. 130. MM2. A hydrocarbon force field utilizing V1 and V2 torsional terms. J Am Chem Soc 99:8127–8134. doi:10.1021/ja00467a001

    Article  CAS  Google Scholar 

  24. Allinger NL, Yuh YH, Lii JH (1989) Molecular mechanics. The MM3 force field for hydrocarbons. 1. J Am Chem Soc 111:8551–8566. doi:10.1021/ja00205a001

    Article  CAS  Google Scholar 

  25. Weiner SJ, Kollman PA, Case D, Singh UC, Alagona G, Profeta S, Weiner P (1984) A new force field for molecular mechanical simulation of nucleic acids and proteins. J Am Chem Soc 106:765–784. doi:10.1021/ja00315a051

    Article  CAS  Google Scholar 

  26. Weiner SJ, Kollman PA, Nguyen NT, Case DA (1986) An all atom force-field for simulations of proteins and nucleic-acids. J Comput Chem 7:230–252. doi:10.1002/jcc.540070216

    Article  CAS  Google Scholar 

  27. Jorgensen WL, Tirado-Rives J (1988) The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. J Am Chem Soc 110:1657–1666. doi:10.1021/ja00214a001

    Article  CAS  Google Scholar 

  28. Jorgensen L, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926–935. doi:10.1063/1.445869

    Article  CAS  Google Scholar 

  29. Halgren TA (1999) MMFF VI. MMFF94s option for energy minimization studies. J Comput Chem 20:720–729. doi:0.1002/(SICI)1096-987X(199905)20:7<720::AID-JCC7>3.0.CO;2-X/abstract

    Article  CAS  Google Scholar 

  30. Polak E, Ribiere G (1969) Note sur la convergence de methods de directions conjuguès. Revenue Francàise Informat Recherche Operationnelle 16:35–43

    Google Scholar 

  31. Cimino P, Gomez-Paloma L, Duca D, Riccio R, Bifulco G (2004) Comparison of different theory models and basis sets in the calculation of 13C NMR chemical shifts of natural products. Magn Reson Chem 42:S26–S33. doi:10.1002/mrc.1410

    Article  PubMed  CAS  Google Scholar 

  32. Young DC (2001) Computational chemistry. Wiley, New York

    Book  Google Scholar 

  33. Møller C, Plesset MS (1934) Note on an approximation treatment for many-electron systems. Phys Rev 46:618–622. doi:10.1103/PhysRev.46.618

    Article  Google Scholar 

  34. Head-Gordon M, Pople JA, Frisch MJ (1988) MP2 energy evaluation by direct methods. Chem Phys Lett 153:503–506. doi:10.1016/0009-2614(88)85250-3

    Article  CAS  Google Scholar 

  35. Hohenberg P, Kohn W (1964) Inhomogeneous electron gas. Phys Rev B 136:B864–B871. doi:10.1103/PhysRev.136.B864

    Article  Google Scholar 

  36. Kohn W, Sham LJ (1965) Self-consistent equations including exchange and correlation effects. Phys Rev A 140:A1133–A1138. doi:10.1103/PhysRev.140.A1133

    Google Scholar 

  37. Adamo C, Barone V (1998) Exchange functionals with improved long-range behavior and adiabatic connection methods without adjustable parameters: the mPW and mPW1PW models. J Chem Phys 108:664–675. doi:10.1063/1.475428

    Article  CAS  Google Scholar 

  38. Adamo C, Barone V (1999) Toward reliable density functional methods without adjustable parameters: the PBE0 model. J Chem Phys 110:6158–6170. doi:10.1063/1.478522

    Article  CAS  Google Scholar 

  39. Zhao Y, Schultz NE, Truhlar DG (2005) Exchange-correlation functionals with broad accuracy for metallic and nonmetallic compounds, kinetics, and noncovalent interactions. J Chem Phys 123:161103-1–161103-4. doi:10.1063/1.2126975

    Google Scholar 

  40. Zhao Y, Schultz NE, Truhlar DG (2006) Design of density functionals by combining the method of constraint satisfaction with parametrization for thermochemistry, thermochemical kinetics, and noncovalent interactions. J Chem Theory Comput 2:364–382. doi:10.1021/ct0502763

    Article  Google Scholar 

  41. Zhao Y, Truhlar DG (2008) Density functionals with broad applicability in chemistry. Acc Chem Res 41:157–167. doi:10.1021/ar700111a

    Article  PubMed  CAS  Google Scholar 

  42. www.gaussian.com. Accessed 04 Nov 2011

  43. www.hyper.com. Accessed 04 Nov 2011

  44. http://www.schrodinger.com/. Accessed 04 Nov 2011

  45. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery Jr JA, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Bakken V. Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Came R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng C Y, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2004) Gaussian 03, Revision E.01. Gaussian, Inc., Wallingford CT

    Google Scholar 

  46. Cheeseman JR, Trucks GW, Keith TA, Frisch MJ (1996) A comparison of models for calculating nuclear magnetic resonance shielding tensors. J Chem Phys 104:5497–5509. doi:10.1063/1.471789

    Article  CAS  Google Scholar 

  47. (a) Kutzelnigg W (1980) Theory of magnetic susceptibilities and NMR chemical shifts in terms of localized quantities. Isr J Chem 19:193–200; (b) Schindler M, Kutzelnigg W (1982) Theory of magnetic susceptibilities and NMR chemical shifts in terms of localized quantities. II. Application to some simple molecules. J Chem Phys 76:1919–1933. doi:10.1063/1.443165

    Google Scholar 

  48. Hansen AE, Bouman TD (1985) Localized orbital/local origin method for calculation and analysis of NMR shieldings. Applications to 13C shielding tensors. J Chem Phys 82:5035–5047. doi:10.1063/1.448625

    Article  CAS  Google Scholar 

  49. Keith TA, Bader RFW (1993) Calculation of magnetic response properties using a continuous set of gauge transformations. Chem Phys Lett 210:223–231. doi:10.1016/0009-2614(93)89127-4

    Article  CAS  Google Scholar 

  50. Ditchfield RJ (1972) Molecular orbital theory of magnetic shielding and magnetic susceptibility. J Chem Phys 56:5688–5691. doi:10.1063/1.1677088

    Article  CAS  Google Scholar 

  51. Wolinski K, Hinton JF, Pulay P (1990) Efficient implementation of the gauge-independent atomic orbital method for NMR chemical shift calculations. J Am Chem Soc 112:8251–8260. doi:10.1021/ja00179a005

    Article  CAS  Google Scholar 

  52. Helgaker T, Jaszuński M, Ruud K (1999) Ab initio methods for the calculation of NMR shielding and indirect spin − spin coupling constants. Chem Rev 99:293–352. doi:10.1021/cr960017t

    Article  PubMed  CAS  Google Scholar 

  53. Ernzerhof M, Perdew JP, Burke K (1997) Coupling-constant dependence of atomization energies. Int J Quantum Chem 64:285–295. doi:10.1002/(SICI)1097-461X(1997)64:3<285::AID-QUA2>3.0.CO;2-S/abstract

    Article  CAS  Google Scholar 

  54. Ernzerhof M, Scuseria GE (1999) Assessment of the Perdew–Burke–Ernzerhof exchange-correlation functional. J Chem Phys 110:5029–5036. doi:10.1063/1.478401

    Article  CAS  Google Scholar 

  55. Sarotti AM, Pellegrinet SC (2009) A multi-standard approach for GIAO 13C NMR calculations. J Org Chem 74:7254–7260. doi:10.1021/jo901234h

    Article  PubMed  CAS  Google Scholar 

  56. Smith SG, Goodman JM (2010) Assigning stereochemistry to single diastereoisomers by GIAO NMR calculation: The DP4 probability. J Am Chem Soc 132:12946–12959. doi:10.1021/ja105035r

    Article  PubMed  CAS  Google Scholar 

  57. Bassarello C, Zampella A, Monti MC, Gomez-Paloma L, D’Auria MV, Riccio R, Bifulco G (2006) Quantum mechanical calculation of coupling constants in the configurational analysis of flexible systems: determination of the configuration of callipeltin A. Eur J Org Chem 604–609. doi:10.1002/ejoc.200500740

    Google Scholar 

  58. Bifulco G, Bassarello C, Riccio R, Gomez-Paloma L (2004) Quantum mechanical calculations of NMR J coupling values in the determination of relative configuration in organic compounds. Org Lett 6:1025–1028. doi:10.1021/ol049913e

    Article  PubMed  CAS  Google Scholar 

  59. Cramer CJ (2004) Essentials of computational chemistry. Wiley, Chichester

    Google Scholar 

  60. Bagno A, Rastrelli F, Saielli G (2005) NMR techniques for the investigation of solvation phenomena and non-covalent interactions. Prog Nucl Magn Reson Spectrosc 47:41–93. doi:10.1016/j.pnmrs.2005.08.001

    Article  CAS  Google Scholar 

  61. Aidas K, Møgelhøj A, Kjær K, Nielsen CB, Mikkelsen KV, Ruud K, Christiansen O, Kongsted J (2007) Solvent effects on NMR isotropic shielding constants. A comparison between explicit polarizable discrete and continuum approaches. J Phys Chem A 111:4199–4210. doi:10.1021/jp068693e

    Article  PubMed  CAS  Google Scholar 

  62. Dračínský M, Bouř P (2010) Computational analysis of solvent effects in NMR spectroscopy. J Chem Theory Comput 6:288–299. doi:10.1021/ct900498b

    Article  Google Scholar 

  63. Tomasi J, Mennucci B, Came R (2005) Quantum mechanical continuum solvation models. Chem Rev 105:2999–3093. doi:10.1021/cr9904009

    Article  PubMed  CAS  Google Scholar 

  64. Klamt A, Schüürmann G (1993) COSMO: a new approach to dielectric screening in solvents with explicit expressions for the screening energy and its gradient. J Chem Soc Perkin Trans 2:799–805. doi:10.1039/P29930000799

    Google Scholar 

  65. Qiu D, Shenkin PS, Hollinger FP, Still WC (1997) The GB/SA continuum model for solvation. A fast analytical method for the calculation of approximate born radii. J Phys Chem A 101:3005–3014. doi:10.1021/jp961992r

    Article  CAS  Google Scholar 

  66. Manzo E, Gavagnin M, Bifulco G, Cimino P, Di Micco S, Ciavatta ML, Guoc YW, Cimino G (2007) Aplysiols A and B, squalene-derived polyethers from the mantle of the sea hare Aplysia dactylomela. Tetrahedron 63:9970–9978. doi:10.1016/j.tet.2007.07.055

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Via Ponte Don Melillo, 84084, Fisciano (Salerno), Italy

    Simone Di Micco, Maria Giovanna Chini, Raffaele Riccio & Giuseppe Bifulco

Authors
  1. Simone Di Micco
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  2. Maria Giovanna Chini
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  3. Raffaele Riccio
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  4. Giuseppe Bifulco
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Corresponding authors

Correspondence to Raffaele Riccio or Giuseppe Bifulco .

Editor information

Editors and Affiliations

  1. Facoltà di Farmacia, Dipto. Chimica delle Sostanze Naturali, Università di Napoli, Via Domenico Montesano 49, Napoli, 80131, Italy

    Ernesto Fattorusso

  2. Scripps Inst. Oceanography, University of California, San Diego, Gilman Drive 9500, La Jolla, 92093-0213, California, USA

    William H. Gerwick

  3. Facoltà di Farmacia, Dipto. Chimica delle Sostanze Naturali, Università di Napoli, Via Domenico Montesano 49, Napoli, 80131, Italy

    Orazio Taglialatela-Scafati

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Micco, S.D., Chini, M.G., Riccio, R., Bifulco, G. (2012). Quantum Chemical Calculation of Chemical Shifts in the Stereochemical Determination of Organic Compounds: A Practical Approach. In: Fattorusso, E., Gerwick, W., Taglialatela-Scafati, O. (eds) Handbook of Marine Natural Products. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3834-0_10

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