DFT Based Quantum Chemical Descriptors of 1-Substituted THβC, DHβC, βC Derivatives

Goncagul Serdaroglu; Mustafa Elık

doi:10.17776/csj.349241

Research Article

DFT Based Quantum Chemical Descriptors of 1-Substituted THβC, DHβC, βC Derivatives

Year 2017, Volume: 38 Issue: 4, 647 - 660, 08.12.2017

Goncagul Serdaroglu , Mustafa Elık

https://doi.org/10.17776/csj.349241

Cited By: 9

Abstract

This research has
focused on the chemical reactivity behavior of N-1 substituted βCCM derivatives
which are isolated from natural or synthetically sources. These compounds as
antitumor agents have an important role in human cancer cell lines as well as antiviral,
antimalarial activity and so on. Geometry optimizations have been conducted by
using DFT method with several basis sets and in 10 different solvent
environments. The Isodensity version of Polarized Continuum Model has been used
to evaluate the solvent effect on chemical stability and its related
properties. We can suggest that global reactivity descriptors can be used to
get the relationship between aromaticity and chemical behavior: the structure
unit 2 and its corresponding substituted structures are the most stable
structures thermodynamically because these structures are more aromatic than
those of the others. The electrostatic potential value on the
electron density surface have changed in following order: 2A (-9.696e^-2)
< 0A (-9.689e^-2) < 1A
(-9.343e^-2) of each
molecule including anthracene 9-yl substituted and have changed as 2 (-0.128)
< 0 (-0.123) < 1 (-0.114) for corresponding
non-substituted structures, at 6311++g(d,p) basis set in water phase. Hopefully,
this paper will provide the useful information on evaluation or explanation of
chemical properties of the antitumor agents used in cancer treatment.

Keywords

Global hardness, electrophilicity, chemical potential, solvent effect, substituent effect

References

[1] Songh H., Liu Y., Liu Y, Wang L., Wang Q. Synthesis and Antiviral and Fungicidal Activity Evaluation of β‑Carboline, Dihydro-β-carboline, Tetrahydro-β-carboline Alkaloids. Journal of Agricultural and Food Chemistry 2014; 62: 1010-1018.
[2] Laine A.E, Lood C, Koskinen A.M.P., Pharmacological Importance of Optically Active Tetrahydro-β-carbolines and Synthetic Approaches to Create the C1 Stereocenter. Molecules 2014; 19: 1544-1567.
[3] Braestrup C, Nielsen M, Olsen C.E., Urinary and brain β-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors. Neurobiology 1980; 77(4):2288-2292.
[4] Hagen T.J., Skolnick P, Cook J.M., Synthesis of 6-Substituted β -Carbolines That Behave as Benzodiazepine Receptor Antagonists or Inverse Agonists. J. Med. Chem.1987; 30: 750-753.
[5] Dodd R.H., Ouannes C, Potier M.C., Carvalho L.P., Rossier J., Potiert P., Synthesis of β -Carboline-Benzodiazepine Hybrid Molecules: Use of the Known Structural Requirements for Benzodiazepine and β -Carboline Binding in Designing a Novel, High-Affinity Ligand for the Benzodiazepine Receptor. J. Med. Chem.1987; 30: 1248-1254.
[6] Cain M, Weber R.W., Guzman F.., Cook J.M., Barker S.A., Rice KC., Crawley J.N., Pau1 S.M., Skolnick P. β-Carbolines: Synthesis and Neurochemical and Pharmacological Actions on Brain Benzodiazepine Receptors. J. Med. Chem. 1982; 25:1081-1091.
[7] Lippke K.P., Schunack W.G., Wenning W., Muller W.E., β -Carbolines as Benzodiazepine Receptor Ligands. 1. Synthesis and Benzodiazepine Receptor Interaction of Esters of β -Carboline-3-carboxylic Acid. J. Med. Chem.1983; 26: 499-503.
[8] Sharma S.D., Bhaduri S., Kaur G., Diastereoselective synthesis of 1,3 disubstituted 1,2,3,4 tetrahydro-β- Carbolines using Pictet- Spengler reaction in non- acidic aprotic media. Indian Journal of Chemistry 2006;45B: 2710-2715
[9] Dong J., Meng T.Z., Shi X.X., Zou W.H., Lu X. Highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted tetrahydro-β-carbolines into (1S,3R)-trans-1,3-disubstituted tetrahydro-β-carbolines: an improved asymmetric synthesis of tadalafil from L-tryptophan. Tetrahedron: Asymmetry 2013; 24: 883-893.
[10] Martin L., Leon A., Martin M.A., Castillo B.., Menendez J.C., Detection and characterization of cyclodextrin complexes with β-carboline derivatives by spectroscopic techniques. Journal of Pharmaceutical and Biomedical Analysis 2003; 32: 991-1001.
[11] Cao R., Fan W., Guo L., Ma Q., Zhang G., Li J., Chen X., Ren Z., Qiu L. Synthesis and structureeactivity relationships of harmine derivatives as potential antitumor agents European Journal of Medicinal Chemistry 2013; 60: 135-143.
[12] Savariz F.C., Foglio M.A., Carvalho J.E., Ruiz A.L.T.G., Duarte M.C.T., Rosa M.F., Meyer E., Sarragiotto M.H., Synthesis and Evaluation of New β-Carboline-3-(4-benzylidene)-4H-oxazol-5-one Derivatives as Antitumor Agents. Molecules 2012; 17: 6100-6113.
[13] Cao R., Peng W., Chen H., Hou X., Guan H., Chen Q., Ma Y., Xu A., Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted β-carboline derivatives. European Journal of Medicinal Chemistry 2005;40: 249-257
[14] Bai B., Li X.Y., Liu L., Li Y., Zhu H.J., Syntheses of novel β-carboline derivatives and the activities against five tumor-cell lines. Bioorganic & Medicinal Chemistry Letters 2014;24: 96-98.
[15] Bai B., Li X.Y., Liu L.., Li Y, Zhu H.J., Design, synthesis and cytotoxic activities of novel β -amino alcohol derivatives. Bioorganic & Medicinal Chemistry Letters 2011; 21: 2302–2304.
[16] Shen Y.C., Chen C.Y., Hsieh P.W., Duh C.Y., Lin Y.M., Ko C.L., The Preparation and Evaluation of 1-Substituted 1,2,3,4-Tetrahydro- and 3,4-Dihydro- β -carboline Derivatives as Potential Antitumor Agents. Chem. Pharm. Bull. 2005;53(1): 32- 36.
[17] Allen M.S., Tan Y.C., Trudell M.L., Narayanan K., Schindler L.R., Martin MJ, Schultz C, Hagen TJ, Koehler K.F., Codding PW, Skolnick P., Cook J. M., Synthetic and Computer-Assisted Analyses of the Pharmacophore for the Benzodiazepine Receptor Inverse Agonist Site. J. Med. Chem. 1990;33: 2343-2357.
[18] Allen M.S, LaLoggia A.J., Darn L.J., Martin M.J., Costantino G., Hagen T.J., Koehler K.F., Skolnick J.P., Cook J.M., Predictive Binding of β -Carboline Inverse Agonists and Antagonists via the CoMFA/GOLPE Approach. J. Med. Chem. 1992;35: 4001-4010.
[19] Frisch M.J., Trucks G.W., Schlegel H.B., Scuseria G.E., Robb M.A., Cheeseman J.R.., Scalmani G, Barone V., Mennucci B., Petersson G.A., Nakatsuji H., Caricato M., Li X., Hratchian H.P., Izmaylov A.F., Bloino J., Zheng G., Sonnenberg J.L., Hada M., Ehara M., Toyota K., Fukuda R., Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai H., Vreven T., Montgomery J.A. Jr., Peralta J.E., Ogliaro F., Bearpark M., Heyd J.J., Brothers E., Kudin K.N., Staroverov V.N., Keith T., Kobayashi R., Normand J., Raghavachari K., Rendell A., Burant J.C., Iyengar S.S., Tomasi J., Cossi M., Rega N., Millam J.M., Klene M., Knox J.E., Cross J.B., Bakken V., Adamo C., Jaramillo J., Gomperts R., Stratmann R.E., Yazyev O., Austin A..J, Cammi R., Pomelli C., Ochterski J.W., Martin R.L., Morokuma K., Zakrzewski V.G.., Voth GA., Salvador P., Dannenberg J..J, Dapprich S., Daniels A.D., Farkas O., Foresman J.B., Ortiz J.V., Cioslowski J., Fox D.J., (2013) Gaussian 09 D.01. Gaussian, Inc, Wallingford CT.
[20] Becke A.D., A new mixing of Hartree–Fock and local density‐functional theories. J Chem Phys 1993;98: 1372-1377.
[21] Lee C., Yang W., Parr R.G., Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev 1988; B37: 785-789.
[22] Foresman J.B., Keith T.A., Wiberg K.B, Snoonian J., Frisch M.J., Solvent Effects. 5. Influence of Cavity Shape, Truncation of Electrostatics, and Electron Correlation on ab Initio Reaction Field Calculations. J Phys Chem 1996; 100: 16098-16104.
[23] Tomasi J., Mennuci B., Cammi R., Quantum Mechanical Continuum Solvation Models. Chem Rev 2005;105: 2999-3093.
[24] Fukui K., Role of frontier orbitals in chemical reactions. Science 1982; 218(4574): 747-754.
[25] Jensen F., Introduction to Computational Chemistry, John Wiley and Sons Ltd., West Sussex, Chapter 6, p. 257, 2007.
[26] Parr R.G., Szentpaly L.V., Liu S., Electrophilicity Index. J. Am. Chem. Soc.1999;121: 1922-1924.
[27] Wiberg K.B., Properties of Some Condensed Aromatic Systems. J. Org. Chem. 1997;62: 5720-5727.

1-Sübstitüeli THβC, DHβC, βC Türevlerinin DFT’ye Dayalı Kuantum Kimyasal Tanımlayıcıları

Year 2017, Volume: 38 Issue: 4, 647 - 660, 08.12.2017

Goncagul Serdaroglu , Mustafa Elık

https://doi.org/10.17776/csj.349241

Cited By: 9

Abstract

Bu çalışma ile doğal
ya da sentetik olarak elde edilen, N-1 sübstitüeli βCCM türevlerinin
kimyasal davranışları incelenmiştir. Antitumor ajanı olan bu bileşikler,
antiviral ve anti sıtma aktivitelerinin yanı sıra, insan kanser hücreleri için
de önemli bir role sahiptirler. Geometri optimizasyonları farklı temel settler
ile 10 farklı çözücü ortamda DFT kullanılarak yapılmıştır. Kimyasal denge ve
buna bağlı özelliklerin çözücüye bağlı olarak nasıl değiştiğini değerlendirmek
için Polarize Kontinuum Model’in Isodensity versiyonu kullanılmıştır. Kimyasal
davranış ve aromatiklik arasında ki ilişkiyi elde etmek için küresel aktiflik
tanımlayıcılarının kullanılabileceğini önerebiliriz: 2 no’lu temel yapı
ve sübstitüeli türevleri, diğer moleküllerden daha aromatik oldukları için,
termodinamiksel olarak daha kararlıdırlar. Antrasen 9-yl sübstitüeli her bir
molekülün elektrostatik potansiyel değerleri 2A (-9.696e^-2)
< 0A (-9.689e^-2) < 1A
(-9.343e^-2) olarak
değişirken, sübstitüe grup içermeyen temel moleküllerin elektrostatik
potansiyelleri 6311++g(d,p) temel set ve sulu fazda 2 (-0.128) < 0 (-0.123)
< 1 (-0.114) olarak hesaplanmıştır. Bu çalışmanın sonuçlarının, kanser
tedavisinde kullanılan antitumor ilaçlarının kimyasal özelliklerinin
açıklanması ve değerlendirilmesi açısından önemli bilgiler sağlayacağını
umuyoruz.

Keywords

Küresel sertlik, elektrofiliklik, kimyasal potansiyel, çözücü etkisi, substituent etkisi

References

[1] Songh H., Liu Y., Liu Y, Wang L., Wang Q. Synthesis and Antiviral and Fungicidal Activity Evaluation of β‑Carboline, Dihydro-β-carboline, Tetrahydro-β-carboline Alkaloids. Journal of Agricultural and Food Chemistry 2014; 62: 1010-1018.
[2] Laine A.E, Lood C, Koskinen A.M.P., Pharmacological Importance of Optically Active Tetrahydro-β-carbolines and Synthetic Approaches to Create the C1 Stereocenter. Molecules 2014; 19: 1544-1567.
[3] Braestrup C, Nielsen M, Olsen C.E., Urinary and brain β-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors. Neurobiology 1980; 77(4):2288-2292.
[4] Hagen T.J., Skolnick P, Cook J.M., Synthesis of 6-Substituted β -Carbolines That Behave as Benzodiazepine Receptor Antagonists or Inverse Agonists. J. Med. Chem.1987; 30: 750-753.
[5] Dodd R.H., Ouannes C, Potier M.C., Carvalho L.P., Rossier J., Potiert P., Synthesis of β -Carboline-Benzodiazepine Hybrid Molecules: Use of the Known Structural Requirements for Benzodiazepine and β -Carboline Binding in Designing a Novel, High-Affinity Ligand for the Benzodiazepine Receptor. J. Med. Chem.1987; 30: 1248-1254.
[6] Cain M, Weber R.W., Guzman F.., Cook J.M., Barker S.A., Rice KC., Crawley J.N., Pau1 S.M., Skolnick P. β-Carbolines: Synthesis and Neurochemical and Pharmacological Actions on Brain Benzodiazepine Receptors. J. Med. Chem. 1982; 25:1081-1091.
[7] Lippke K.P., Schunack W.G., Wenning W., Muller W.E., β -Carbolines as Benzodiazepine Receptor Ligands. 1. Synthesis and Benzodiazepine Receptor Interaction of Esters of β -Carboline-3-carboxylic Acid. J. Med. Chem.1983; 26: 499-503.
[8] Sharma S.D., Bhaduri S., Kaur G., Diastereoselective synthesis of 1,3 disubstituted 1,2,3,4 tetrahydro-β- Carbolines using Pictet- Spengler reaction in non- acidic aprotic media. Indian Journal of Chemistry 2006;45B: 2710-2715
[9] Dong J., Meng T.Z., Shi X.X., Zou W.H., Lu X. Highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted tetrahydro-β-carbolines into (1S,3R)-trans-1,3-disubstituted tetrahydro-β-carbolines: an improved asymmetric synthesis of tadalafil from L-tryptophan. Tetrahedron: Asymmetry 2013; 24: 883-893.
[10] Martin L., Leon A., Martin M.A., Castillo B.., Menendez J.C., Detection and characterization of cyclodextrin complexes with β-carboline derivatives by spectroscopic techniques. Journal of Pharmaceutical and Biomedical Analysis 2003; 32: 991-1001.
[11] Cao R., Fan W., Guo L., Ma Q., Zhang G., Li J., Chen X., Ren Z., Qiu L. Synthesis and structureeactivity relationships of harmine derivatives as potential antitumor agents European Journal of Medicinal Chemistry 2013; 60: 135-143.
[12] Savariz F.C., Foglio M.A., Carvalho J.E., Ruiz A.L.T.G., Duarte M.C.T., Rosa M.F., Meyer E., Sarragiotto M.H., Synthesis and Evaluation of New β-Carboline-3-(4-benzylidene)-4H-oxazol-5-one Derivatives as Antitumor Agents. Molecules 2012; 17: 6100-6113.
[13] Cao R., Peng W., Chen H., Hou X., Guan H., Chen Q., Ma Y., Xu A., Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted β-carboline derivatives. European Journal of Medicinal Chemistry 2005;40: 249-257
[14] Bai B., Li X.Y., Liu L., Li Y., Zhu H.J., Syntheses of novel β-carboline derivatives and the activities against five tumor-cell lines. Bioorganic & Medicinal Chemistry Letters 2014;24: 96-98.
[15] Bai B., Li X.Y., Liu L.., Li Y, Zhu H.J., Design, synthesis and cytotoxic activities of novel β -amino alcohol derivatives. Bioorganic & Medicinal Chemistry Letters 2011; 21: 2302–2304.
[16] Shen Y.C., Chen C.Y., Hsieh P.W., Duh C.Y., Lin Y.M., Ko C.L., The Preparation and Evaluation of 1-Substituted 1,2,3,4-Tetrahydro- and 3,4-Dihydro- β -carboline Derivatives as Potential Antitumor Agents. Chem. Pharm. Bull. 2005;53(1): 32- 36.
[17] Allen M.S., Tan Y.C., Trudell M.L., Narayanan K., Schindler L.R., Martin MJ, Schultz C, Hagen TJ, Koehler K.F., Codding PW, Skolnick P., Cook J. M., Synthetic and Computer-Assisted Analyses of the Pharmacophore for the Benzodiazepine Receptor Inverse Agonist Site. J. Med. Chem. 1990;33: 2343-2357.
[18] Allen M.S, LaLoggia A.J., Darn L.J., Martin M.J., Costantino G., Hagen T.J., Koehler K.F., Skolnick J.P., Cook J.M., Predictive Binding of β -Carboline Inverse Agonists and Antagonists via the CoMFA/GOLPE Approach. J. Med. Chem. 1992;35: 4001-4010.
[19] Frisch M.J., Trucks G.W., Schlegel H.B., Scuseria G.E., Robb M.A., Cheeseman J.R.., Scalmani G, Barone V., Mennucci B., Petersson G.A., Nakatsuji H., Caricato M., Li X., Hratchian H.P., Izmaylov A.F., Bloino J., Zheng G., Sonnenberg J.L., Hada M., Ehara M., Toyota K., Fukuda R., Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai H., Vreven T., Montgomery J.A. Jr., Peralta J.E., Ogliaro F., Bearpark M., Heyd J.J., Brothers E., Kudin K.N., Staroverov V.N., Keith T., Kobayashi R., Normand J., Raghavachari K., Rendell A., Burant J.C., Iyengar S.S., Tomasi J., Cossi M., Rega N., Millam J.M., Klene M., Knox J.E., Cross J.B., Bakken V., Adamo C., Jaramillo J., Gomperts R., Stratmann R.E., Yazyev O., Austin A..J, Cammi R., Pomelli C., Ochterski J.W., Martin R.L., Morokuma K., Zakrzewski V.G.., Voth GA., Salvador P., Dannenberg J..J, Dapprich S., Daniels A.D., Farkas O., Foresman J.B., Ortiz J.V., Cioslowski J., Fox D.J., (2013) Gaussian 09 D.01. Gaussian, Inc, Wallingford CT.
[20] Becke A.D., A new mixing of Hartree–Fock and local density‐functional theories. J Chem Phys 1993;98: 1372-1377.
[21] Lee C., Yang W., Parr R.G., Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev 1988; B37: 785-789.
[22] Foresman J.B., Keith T.A., Wiberg K.B, Snoonian J., Frisch M.J., Solvent Effects. 5. Influence of Cavity Shape, Truncation of Electrostatics, and Electron Correlation on ab Initio Reaction Field Calculations. J Phys Chem 1996; 100: 16098-16104.
[23] Tomasi J., Mennuci B., Cammi R., Quantum Mechanical Continuum Solvation Models. Chem Rev 2005;105: 2999-3093.
[24] Fukui K., Role of frontier orbitals in chemical reactions. Science 1982; 218(4574): 747-754.
[25] Jensen F., Introduction to Computational Chemistry, John Wiley and Sons Ltd., West Sussex, Chapter 6, p. 257, 2007.
[26] Parr R.G., Szentpaly L.V., Liu S., Electrophilicity Index. J. Am. Chem. Soc.1999;121: 1922-1924.
[27] Wiberg K.B., Properties of Some Condensed Aromatic Systems. J. Org. Chem. 1997;62: 5720-5727.

There are 27 citations in total.

Details

Primary Language	English
Journal Section	Natural Sciences
Authors	Goncagul Serdaroglu Mustafa Elık
Publication Date	December 8, 2017
Submission Date	February 16, 2017
Acceptance Date	August 16, 2017
Published in Issue	Year 2017Volume: 38 Issue: 4

Cite

APA	Serdaroglu, G., & Elık, M. (2017). DFT Based Quantum Chemical Descriptors of 1-Substituted THβC, DHβC, βC Derivatives. Cumhuriyet Science Journal, 38(4), 647-660. https://doi.org/10.17776/csj.349241