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The study aims to present a detailed theoretical investigation of noncovalent intermolecular interactions between different π–π stacking nitrogen substituted phenothiazine derivatives by applying second-order Møller-Plesset perturbation (MP2), density functional (DFT) and semiempirical theories. The conformational stability of these molecular systems is mainly given by the dispersion-type electron correlation effects. The density functional tight-binding (DFTB) method applied for dimer structures are compared with the results obtained by the higher level theoretical methods. Additionally, the optimal configuration of the investigated supramolecular systems and their self-assembling properties are discussed.

Weak noncovalent intermolecular forces such as hydrogen bonds, π–π stacking play an important role in the formation of stable and structurally well-defined supramolecular structures [

In spite of the fact that parallel-displaced π–π stacking interactions [

In our previous work [

For increasing the self-assembling capability of the organic molecules from the phenothiazine family we propose a new class of nitrogen substituted phenothiazine derivatives with a stronger tendency to self-organize in supramolecular structures. These nitrogen-substituted systems are expected to enhance stacking interactions by polarizing the aromatic ring and thereby promoting electrostatic interactions.

The π–π interactions between benzene and the aromatic nitrogen heterocyclic pyridine, pyrimidine, 1,3,5-triazine, 1,2,3-triazine, 1,2,4,5-tetrazine, and 1,2,3,4,5-pentazine were systematically investigated by the Hobza group [

In the present work, we use computational chemistry to study the stacking interactions between two types of nitrogen-substituted phenothiazine derivative. Information about the stacking contribution in a self-assembling process is difficult to isolate from experimental studies alone. Our calculations allow us to characterize the individual interactions between the nitro-substituted aromatic molecules, and thereby reveal the detailed contribution of different types of interactions giving a comprehensive picture of their stacking abilities.

For the computation of intermolecular interactions, local (L) electron correlation methods [^{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 ^{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 [

In spite of the fact that the local correlation treatment combined with the density-fitting technique can, in general, provide calculations with much lower computational costs, the deficiency of the standard MP2 theory (overestimates the dispersion forces in π-stacked systems) remain also an attendant of the LMP2 method. Hill

The widely used semiempirically corrected DFT method by dispersion effects [

Due to the computer capacity limits, theoretical methods presented in the previous paragraph together with middle large basis sets are capable of handling molecular systems with approximately 150 atoms. At the same time, in the self-assembling processes are involved molecular systems, which all together contain more than 200–300 atoms. The density functional-based tight-binding method combined with the self-consistent charge technique (SCC-DFTB) [_{10} helices in proteins [

Using the DF-LMP2 method implemented in the Molpro program package suite [_{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 [

The intermolecular interaction of dimer structures of the phenothiazine derivatives were investigated in detail in our previous work [

Comparing the conformational energy differences one can observe that the EPT-C2 structure shows a very good stability, being with only 0.497 kcal/mol above to the structure with the highest stability. Unfortunately, this close energetic proximity is not true for the alkyl chains. The difference between the most stable side-parallel structure and the top-parallel geometry (see

Summarizing, the advantageous contribution of the EPT-C2 and the disadvantageous effect of the alkyl chain impose the use of alkyl chains shorter than hexane. In order to overcome the unavoidable destructive effect we changed two and four carbon atoms, respectively with nitrogen in the phenothiazine head-group. By this substitution the strength of the intermolecular interaction is enhanced by diminishing the destructive contribution of the alkyl chains.

According to the statement drew in the previous subsection, we have figured out two different nitrogen substituted molecular structures, called azaphenothizaine (APTZ) and diazaphenothiazine (DAPTZ). Their molecular graphics is presented in

One of the conclusion drew up in our previous work [

The energy results are collected in

We consider that in the first case of APTZ the relative rotation of the monomers is not so significant in order to destroy the predisposition for the self-assembling, but in the second case this rotation could be large enough to break the self-assembling. In a later section we have investigated the probability of this assumption by adding alkyl chains to the nitrogen-substituted head-groups. Comparing the d(N···H) distances (measured between the N atom of the first monomer and the H atom belonging to the N–H bond of the second monomer—see ^{APTZ} = 3.557 Å). The distance d(N···H)^{DAPTZ} increase to 3.598 and reach 3.665 Å for the PTZ dimer.

The nature of the intermolecular energies was analyzed at HF and correlation level of theories. The correlation energy was decomposed in two parts, defined in the framework of the electron correlation theory taking into account the local character of occupied and virtual orbitals [^{HF} = +10.024 kcal/mol. This strong electrostatic repulsion is canceled by a stronger attractive force, mostly given by the dispersion effects (^{Disp.} = −20.378 kcal/mol). Similar situation can be found for DAPTZ dimer. Here, the HF/aug-cc-pVTZ energy is Δ^{HF} = +9.887 kcal/mol, while the electron correlation part is Δ^{Corr} = +24.834 kcal/mol.

In the case of electron correlation calculations the conventional MP2, CCSD(T) and two spin component scaling MP2 methods were considered together with the density-fitting and orbital localization approximations. Considering any of the dimer case, it can be seen that HF curves do not give bounded states, while the potential curves drawn with the help of electron correlation methods show energy minima.

Assuming the fundamental idea of Grimme [

A similar conclusion was obtained also in the case of phenothiazine dimers [

In order to obtain a comprehensive picture of the self-assembling process, one needs to treat the

To make sure about the efficiency of the SCC-DFTB method in our earlier work [

As first step we built dimer structures for both APTZ and DAPTZ molecular species considering for the spacer butane and nonane alkyl chains and a thiol fragment as linker. The starting geometries are based on the equilibrium positions of the two molecular species and the spacer and linker groups were subsequently added.

The optimized dimer geometries for

The values are: 1.49 kcal/mol and 1.84 kcal/mol, respectively. As we can see, there is a significant amount of deformation energy which can weaken the intermolecular interaction and accordingly decrease the conformational energy difference between the ordered and the “defected” structures. Similar molecular geometries were built in the case of DAPTZ-type head-group. The molecular structures with optimized geometry are shown in

Comparing energies corresponding to similar structures, one can conclude that the substitution of the second set of nitrogen atoms does not increase the efficiency of the dimer association. In both cases of

The intermolecular π–π stacking interaction between some PTZ derivatives having attached alkane chains with different lengths have been investigated and described quantitatively in a previous paper [

For instance, two rings from two neighboring PTZ molecules could be coupled together in a molecular structure with five rings and two alkyl chains with variable length (See

This work was funded by the Romanian National Authority for Scientific Research through the CNCSIS Contract PCCE-ID 76. We gratefully acknowledge for technical assistance of Data Center of NIRDIMT Cluj-Napoca.

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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 [

The side-parallel and top-parallel structures of the alkyl chain.

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

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

The intermolecular _{H…N} coordinate in the PTZ dimer.

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

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.

The optimized dimer geometries for

The optimized dimer geometries for

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

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.

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

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 |

| |||||

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 |

The _{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.

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

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

| ||||

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

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