# Nitrogen Substituted Phenothiazine Derivatives: Modelling of Molecular Self-Assembling

^{*}

## Abstract

**:**

## 1. Introduction

## 2. Computational Details

^{2}) without losing much in accuracy compared with the case of the classical second-order Møller-Plesset perturbation theory (MP2), which scales formally with the order of O(N

^{5}). Furthermore, considering the local character of occupied and virtual orbitals in the local correlation treatment, one can easily obtain also the dispersion part (an intermolecular effect) of the correlation contribution [25].

_{10}helices in proteins [36], and the stability of the double-stranded DNA tetramer with a ligand in the intercalative fashion [37].

_{π}atomic orbitals of all 6 carbon atoms from the given six-membered ring. Molecular structures were visualized and analyzed using the open source Gabedit molecular graphics program [42].

## 3. Results and Discussion

#### 3.1. Phenothiazine Dimers

#### 3.2. Nitrogen-Substituted Phenothiazine Dimers

^{APTZ}= 3.557 Å). The distance d(N···H)

^{DAPTZ}increase to 3.598 and reach 3.665 Å for the PTZ dimer.

^{HF}= +10.024 kcal/mol. This strong electrostatic repulsion is canceled by a stronger attractive force, mostly given by the dispersion effects (E

^{Disp.}= −20.378 kcal/mol). Similar situation can be found for DAPTZ dimer. Here, the HF/aug-cc-pVTZ energy is ΔE

^{HF}= +9.887 kcal/mol, while the electron correlation part is ΔE

^{Corr}= +24.834 kcal/mol.

#### 3.3. SCC-DFTB Results

**-**nonyl

**-**APTZ can be seen in Figure 8/A3. The intermolecular interaction energy is −20.08 kcal/mol, slightly lower that for the highly-ordered structure. In addition, we have computed also the energy difference between the ordered (A2) and the “defected” (A3) configurations as well as the energy of the monomer deformation (A3).

## 4. Conclusions

## Acknowledgments

## References

- Hollingsworth, MD. Crystal Engineering: from Structure to Function. Science
**2002**, 295, 2410–2413. [Google Scholar] - Leininger, S; Olenyuk, B; Stang, PJ. Self-Assembly of Discrete Cyclic Nanostructures Mediated by Transition Metals. Chem. Rev
**2000**, 100, 853–908. [Google Scholar] - Venkataramanan, B; Saifudin, M-A; Jagadese, VJ; Suresh, V. Self-assembly of methacrylamides assisted by an interplay of N–H···O, C–H···O, C–H···π and π–π interactions. Cryst. Eng. Commun
**2004**, 6, 284–289. [Google Scholar] - Colquhoun, HM; Zhu, Z; Cardin, CJ; Gan, Y; Drew, MGB. Sterically Controlled Recognition of Macromolecular Sequence Information by Molecular Tweezers. J. Am. Chem. Soc
**2007**, 129, 16163–16174. [Google Scholar] - Burley, SK; Petsko, GA. Aromatic-aromatic interaction: A mechanism of protein structure stabilization. Science
**1985**, 229, 23–28. [Google Scholar] - Loakes, D. The applications of universal DNA base analogues. Nucleic Acids Res
**2001**, 29, 2437–2447. [Google Scholar] - Rutledge, LR; Campbell-Verduyn, LS; Wetmore, SD. Characterization of the stacking interactions between DNA or RNA nucleobases and the aromatic amino acids. Chem. Phys. Lett
**2007**, 444, 167–175. [Google Scholar] - Hunter, CA; Sanders, KM. The nature of π–π interactions. J. Am. Chem. Soc
**1990**, 112, 5525–5534. [Google Scholar] - Járai-Szabó, F; Aştilean, S; Néda, Z. Understanding self-assembled nanosphere patterns. Chem. Phys. Lett
**2005**, 408, 241–246. [Google Scholar] - Love, JC; Estroff, LA; Kriebel, JK; Nuzzo, RG; Witheside, GM. Self-Assembled Monolayers of Thiolates on Metals as a Form of Nanotechnology. Chem. Rev
**2005**, 105, 1103–1170. [Google Scholar] - Bende, A; Grosu, I; Turcu, I. Molecular modeling of phenothiazine derivatives: Self-assembling properties. J. Phys. Chem. A
**2010**, 114, 12479–12489. [Google Scholar] - Wang, W; Hobza, P. Theoretical Study on the Complexes of Benzene with Isoelectronic Nitrogen-Containing Heterocycles. ChemPhysChem
**2008**, 9, 1003–1009. [Google Scholar] - Mignon, P; Loverix, S; Steyaert, J; Geerlings, P. Influence of the π–π interaction on the hydrogen bonding capacity of stacked DNA/RNA bases. Nucl. Acid. Res
**2005**, 33, 1779–1789. [Google Scholar] - Mignon, P; Loverix, S; de Proft, F; Geerlings, P. Influence of Stacking on Hydrogen Bonding: Quantum Chemical Study on Pyridine-Benzene Model Complexes. J. Phys. Chem. A
**2004**, 108, 6038–6044. [Google Scholar] - Mishra, BK; Arey, JS; Sathyamurthy, N. Stacking and Spreading Interaction in N-Heteroaromatic Systems. J. Phys. Chem. A
**2010**, 114, 9606–9616. [Google Scholar] - Główka, ML; Martynowski, D; Kozłowska, K. Stacking of six-membered aromatic rings in crystals. J. Mol. Struct
**1999**, 474, 81–89. [Google Scholar] - Wheaton, CA; Dobrowolski, SL; Millen, AL; Wetmore, SD. Nitrosubstituted aromatic molecules as universal nucleobases: Computational analysis of stacking interactions. Chem. Phys. Lett
**2006**, 428, 157–166. [Google Scholar] - Pulay, P. Localizability of dynamic electron correlation. Chem. Phys. Lett
**1983**, 100, 151–154. [Google Scholar] - Saebo, S; Pulay, P. Local Treatment of Electron Correlation. Annu. Rev. Phys. Chem
**1993**, 44, 213–236. [Google Scholar] - Hampel, C; Werner, H-J. Local treatment of electron correlation in coupled cluster theory. J. Chem. Phys
**1996**, 104, 6286–6297. [Google Scholar] - Hetzer, G; Schütz, M; Stoll, H; Werner, H-J. Low-order scaling local correlation methods II: Splitting the Coulomb operator in linear scaling local second-order MøllerPlesset perturbation theory. J. Chem. Phys
**2000**, 113, 9443–9455. [Google Scholar] - Schütz, M. Low-order scaling local electron correlation methods. III. Linear scaling local perturbative triples correction (T). J. Chem. Phys
**2000**, 113, 9986–10001. [Google Scholar] - Schütz, M; Werner, H-J. Low-order scaling local electron correlation methods. IV. Linear scaling local coupled-cluster (LCCSD). J. Chem. Phys
**2001**, 114, 661–681. [Google Scholar] - Vahtras, O; Almlöf, J; Feyereisen, MW. Integral approximations for LCAO-SCF calculations. Chem. Phys. Lett
**1993**, 213, 514–518. [Google Scholar] - Schütz, M; Rauhut, G; Werner, HJ. Local Treatment of Electron Correlation in Molecular Clusters: Structures and Stabilities of (H
_{2}O)_{n}, n = 2–4. J. Phys. Chem. A**1998**, 102, 5997–6003. [Google Scholar] - Hill, JG; Platts, JA; Werner, H-J. Calculation of intermolecular interactions in the benzene dimer using coupled-cluster and local electron correlation methods. Phys. Chem. Chem. Phys
**2006**, 8, 4072–4078. [Google Scholar] - Grimme, S. Improved second-order Møller-Plesset perturbation theory by separate scaling of parallel and antiparallel-spin pair correlation energies. J. Chem. Phys
**2003**, 118, 9095–10002. [Google Scholar] - Hill, JG; Platts, JA. Spin-Component Scaling Methods for Weak and Stacking Interactions. J. Chem. Theory Comput
**2007**, 3, 80–85. [Google Scholar] - Jurečka, P; Šponer, J; Černý, J; Hobza, P. Benchmark database of accurate (MP2 and CCSD(T) complete basis set limit) interaction energies of small model complexes, DNA base pairs, and amino acid pairs. Phys. Chem. Chem. Phys
**2006**, 8, 1985–1993. [Google Scholar] - Distasio, RA, Jr; Head-Gordon, M. Optimized spin-component scaled second-order Møller-Plesset perturbation theory for intermolecular interaction energies. Mol. Phys
**2007**, 105, 1073–1083. [Google Scholar] - Grimme, S. Semiempiricall GGA-type density functional constructed with a long-range dispersion correction. J. Comput. Chem
**2006**, 27, 1787–1799. [Google Scholar] - Elstner, M; Porezag, D; Jungnickel, G; Elsner, J; Haugk, M; Frauenheim, T; Suhai, S; Seifert, G. Self-consistent-charge density-functional tight-binding method for simulations of complex materials properties. Phys. Rev. B
**1998**, 58, 7260–7268. [Google Scholar] - Elstner, M; Jalkanen, KJ; Knapp-Mohammady, M; Frauenheim, T; Suhai, S. DFT studies on helix formation in N-acetyl-(l-alanyl)
_{n}-N’-methylamide for n = 1–20. Chem. Phys**2000**, 256, 15–27. [Google Scholar] - Elstner, M; Jalkanen, KJ; Knapp-Mohammady, M; Frauenheim, T; Suhai, S. Energetics and structure of glycine and alanine based model peptides: Approximate SCC-DFTB, AM1 and PM3 methods in comparison with DFT, HF and MP2 calculations. Chem. Phys
**2001**, 263, 203–219. [Google Scholar] - Elstner, M; Hobza, P; Frauenheim, T; Suhai, S; Kaxiras, E. Hydrogen bonding and stacking interactions of nucleic acid base pairs: A density-functional-theory based treatment. J. Chem. Phys
**2001**, 114, 5149–5155. [Google Scholar] - Liu, HY; Elstner, M; Kaxiras, E; Frauenheim, T; Hermans, J; Yang, WT. Quantum mechanics simulation of protein dynamics on long timescale. Proteins: Struct. Funct., Bioinf
**2001**, 44, 484–489. [Google Scholar] - Kubař, T; Jurečka, P; Černý, J; Řezáč, J; Otyepka, M; Valdés, H; Hobza, P. Density-Functional, Density-Functional Tight-Binding, and Wave Function Calculations on Biomolecular Systems. J. Phys. Chem. A
**2007**, 111, 5642–5647. [Google Scholar] - Werner, H-J; Knowles, PJ; Lindh, R; Manby, FR; Schütz, M; Celani, P; Korona, T; Mitrushenkov, A; Rauhut, G; Adler, TB; et al. MOLPRO, a Package of ab initio Programs, version 2009.1. Available online: http://www.molpro.net (accessed on 11 May 2011).
- Dunning, TH, Jr. Gaussian basis sets for use in correlated molecular calculations. I. The atoms boron through neon and hydrogen. J. Chem. Phys
**1989**, 90, 1007–1023. [Google Scholar] - Kendall, RA; Dunning, TH, Jr; Harrison, RJ. Electron affinities of the first-row atoms revisited. Systematic basis sets and wave functions. J. Chem. Phys
**1992**, 96, 6796–6806. [Google Scholar] - Pipek, J; Mezey, PG. A fast intrinsic localization procedure applicable for ab initio and semiempirical linear combination of atomic orbital wave functions. J. Chem. Phys
**1989**, 90, 4916–4926. [Google Scholar] - Allouche, AR. Gabedit—A graphical user interface for computational chemistry softwares. J. Comput. Chem
**2010**, 32, 174–182. [Google Scholar] - Korth, M; Pitoňák, M; Řezáč, J; Hobza, P. A Transferable H-Bonding Correction for Semiempirical Quantum-Chemical Methods. J. Chem. Theory Comput
**2010**, 6, 344–352. [Google Scholar] - Allinger, NL; Lii, J-H. Molecular mechanics. The MM3 force field for hydrocarbons. 3. The van der Waals’ potentials and crystal data for aliphatic and aromatic hydrocarbons. J. Am. Chem. Soc
**1989**, 111, 8576–8582. [Google Scholar]

**Figure 1.**Conformational structures and their relative conformational energies for different ethyl-phenothiazine (EPT) dimers obtained at the DF-LMP2/cc-pVTZ level of theory. (See Reference [11]).

**Figure 3.**The optimized geometry structure of the azaphenothizaine (APTZ) and diazaphenothiazine (DAPTZ) molecules.

**Figure 4.**The optimized geometry structure of the azaphenothizaine (APTZ) and diazaphenothiazine (DAPTZ) dimers.

**Figure 6.**The potential energy curves for azaphenothizaine (APTZ) and diazaphenothiazine (DAPTZ) dimers obtained at different theoretical methods and using the cc-pVDZ basis set.

**Figure 7.**The potential energy curves for phenothiazine (PTZ), azaphenothizaine (APTZ) and diazaphenothiazine (DAPTZ) dimers obtained at DF-SCSN-LMP2 theoretical method and using the cc-pVDZ basis set.

**Figure 8.**The optimized dimer geometries for thiol-butyl-APTZ (

**A1**) and for two configurations of thiol-nonyl-APTZ (

**A2**and

**A3**) obtained at SCC-DFTB level of theory.

**Figure 9.**The optimized dimer geometries for thiol-butyl-DAPTZ (

**B1**) and for two configurations of thiol-nonyl-DAPTZ (

**B2**and

**B3**) obtained at SCC-DFTB level of theory.

**Figure 10.**The hypothetically designed structure obtained by partial superposition of two PTZ units with two alkyl chains attached to nitrogen atoms.

**Table 1.**Intermolecular interaction energies and their characteristic components (dispersion and ionic) defined in the framework of the LMP2 theory obtained at HF and LMP2 levels of theory and different basis sets.

ΔE^{HF} (kcal/mol) | ΔE^{DF-LMP2} (kcal/mol) | E^{Corr.} (kcal/mol) | E^{Disp.} (kcal/mol) | E^{Ion.} (kcal/mol) | |
---|---|---|---|---|---|

APTZ | |||||

cc-pVDZ | +7.056 | −9.343 | −16.399 | −13.854 | −3.462 |

cc-pVTZ | +9.307 | −12.322 | −21.629 | −17.741 | −5.312 |

aug-cc-pVDZ | +7.136 | −15.245 | −22.381 | −19.777 | −6.723 |

aug-cc-pVTZ | +10.024 | −15.138 | −25.162 | −20.378 | −6.117 |

DAPTZ | |||||

cc-pVDZ | +6.445 | −9.696 | −16.141 | −14.044 | −3.625 |

cc-pVTZ | +8.992 | −12.338 | −21.330 | −17.806 | −5.485 |

aug-cc-pVDZ | +7.616 | −14.714 | −22.330 | −19.807 | −6.926 |

aug-cc-pVTZ | +9.887 | −14.947 | −24.834 | −20.397 | −6.232 |

**Table 2.**The R

_{H…N}equilibrium distances and the corresponding intermolecular interaction energies for azaphenothizaine (APTZ) and diazaphenothiazine (DAPTZ) dimers obtained at different theoretical methods and using the cc-pVDZ basis set.

LMP2 | LCCSD(T) | LMP2-SCS | LMP2-SCSN | |
---|---|---|---|---|

APTZ | ||||

R_{e} (Å) | 3.564 | 3.585 | 3.700 | 3.656 |

E_{e} (kcal/mol) | −9.287 | −8.888 | −5.999 | −7.097 |

DAPTZ | ||||

R_{e} (Å) | 3.605 | 3.622 | 3.728 | 3.680 |

E_{e} (kcal/mol) | −9.606 | −9.277 | −6.257 | −7.603 |

© 2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).

## Share and Cite

**MDPI and ACS Style**

Bende, A.; Turcu, I.
Nitrogen Substituted Phenothiazine Derivatives: Modelling of Molecular Self-Assembling. *Int. J. Mol. Sci.* **2011**, *12*, 3102-3116.
https://doi.org/10.3390/ijms12053102

**AMA Style**

Bende A, Turcu I.
Nitrogen Substituted Phenothiazine Derivatives: Modelling of Molecular Self-Assembling. *International Journal of Molecular Sciences*. 2011; 12(5):3102-3116.
https://doi.org/10.3390/ijms12053102

**Chicago/Turabian Style**

Bende, Attila, and Ioan Turcu.
2011. "Nitrogen Substituted Phenothiazine Derivatives: Modelling of Molecular Self-Assembling" *International Journal of Molecular Sciences* 12, no. 5: 3102-3116.
https://doi.org/10.3390/ijms12053102