Investigation of different SWCNTs interaction with dopamine and serotonin anticancers: a theoretical study Investigación de la interacción de diferentes SWCNT con anticancerosos de dopamina y serotonina: un estudio teórico

Carbon nano tubes (CNTS) have two basic structure as single-walled and multi-walled based on hexagonal plexus of carbon atoms. CNTs can serve as platforms to conjugate other compounds specially in medications purposes by immobilization of biomolecules at their surface. Dopamine and serotonin are two biological molecules which have bifunctional activities as hormone and neurotransmitter. These two molecules have important roles as neurotransmitters in the central and peripheral nervous systems but serotonin functions as a mood regulator, while dopamine is connected to the “pleasure center”. In this article we optimized molecular and structural properties of connected dopamine and serotonin with SWNTS with four different diameters (7.0,7.5,7.7 and 10.0 nm) by using molecular quantum methods such as NMR shielding tensor data by B3LYP level of theory with 6-31 G(d) as a basis set, mk and frequency methods. Theoretical computations were performed to study NMR chemical shift data including magnetic shielding tensor (σ, ppm), shielding asymmetry (η), magnetic shielding anisotropy (σaniso), magnetic shielding isotropy (σiso) , skew of a tensor (Κ) and chemical shift anisotropy (Δσ) and span (Ω) at various rotation angles around a specific rotation , physical and chemical properties of atomic nuclei , frequency data by B3LYP/6-31g level of theory and POP method using gaussian 09 program.


INTRODUCTION
Dopamine is a medication form of a substance that occurs naturally in the body based on catecholamine and phenethylamine families and suppose to function both as a hormone and a neurotransmitter (Berridge, 2009). Also, it is known as feel good hormone as the secondary messenger system which sends messages between nerve cells in the braaccouin, binds to receptors in the brain and making them send signals from one cell to another and causes cellular changes that can affect your well-being in a number of ways for instant, in moments of pleasure and reward, we get a rush of dopamine, and when levels are too low, we feel a lack of motivation and feelings of helplessness (Romanelli, 2009;Robinson, 1993).
As Dopamine hormonal function can be mentioned as reduces of secretion of prolactin by stimulating theD2 receptors, thereby affecting milk production (Lindemann,2005) and also in memory consolidation, Dopamine or Dopamine agonists have critical role (Wise, 2004).
Research also highlights that dopamine receptors are found in the kidneys, pancreas, lungs and blood vessels outside the central nervous system and belong to the large family of Heptahelical transmembrane spanning G protein-coupled receptors (GPCRs). By now five mammalian dopamine receptor subtypes have been identified and are classified into two major groups, the D1-like (D1 and D5) which are mostly found in the cerebral cortex, hypothalamus, and thalamus and D2-like (D2, D3, and D4) receptors which are similar in structure but differ by their affinity for dopamine and coupling to downstream effectors like G protein. Gprotein-coupled receptors also regulate the activity of PKB/Akt (protein kinase B) at serine-473 (Ser473) and threonine-308 (Thr308) although the mechanisms of these functions are poorly understood (Xiangdang, 2010). D3 and D4 receptors are less abundant and less widely distributed compared to D2 receptors (Romanelli,2009).
The contribution of dopamine receptor subtypes to increase of sensitization behavior in response to AMPH(Amphetamine) has been widely studied by blocking D1 and D2 receptors during repeated AMPH administration. These studies demonstrate an acute role for D1 receptors and D2 receptors as a supporting or secondary role in the development of AMPH sensitization (Vanderschuren, 2000). Dopamine D1 or D2 receptor agonists despite of neurotrophin receptor stimulation, phosphorylate Akt at the Thr308 residue, not via phosphoinositide 3-kinase (PI3K), but via PKA (protein kinase A) and ERK (extracellular signal-regulated kinase) activation in primary striatal cultures (Brami-Cherrier,2002).
Studies show that Signaling through dopamine receptors adjust neurotic processes such as motoractivity, motivation and reward (including drug-seeking behavior), and highercognition (including working memory) (Kienast, 2006). Dopamine receptors are involved in all of the physiological functions of dopamine such as the autonomic movement, emotion, hormonal regulation, dopamine-induced immune effects, and tumor behavior, and etc. some evidences show that dopamine receptors are associated with the regulation of tumor behavior, including tumor cell death, proliferation, invasion, and migration which cannot only directly affect tumor behavior, but also limit tumor progress via activating tumor immunity (Wang, 2019).
Dopamine and Serotonin have important roles as neurotransmitters in the central and peripheral nervous systems (Deutch,1999) but serotonin functions as a mood regulator, while dopamine is connected to the "pleasure center.".
Serotonin [5-hydroxytryptamine (5-HT)] has an important role in many organs as a peripheral hormone transported by blood platelets and is released upon activation (Berger, 2009;Herr, 2017). This diverse functions of serotonin in the brain are mediated by multiple 5-HT receptor subtypes (15 known subtypes). These subtypes were at first classified based on pure pharmacological criteria ad belong to different families of 5-HT receptors (Peroutka, 1990).5-HT 2and 5-HT1c are structurally similar and therefore have similar biochemical activation consequences and pharmacological profile (Conn, 1984;Conn, 1986;Hoyer, 1988). 5-HT2 and 5-HT1c and the new discovered one (5-HT2f) which lately renamed as 5-HT2A, 5-HT2c and 5-HT2B , demonstrated striking protection in their amino acid sequence, thus claimed that they could have evolved by mutation from a common ancestral gene (Julius, 1988).
As a neurotransmitter, serotonin participate in regulation of sleep, appetite, mood, and other important brain functions which cannot cross form blood-brain-barrier and needs transporter. Peripheral serotonin roles are the regulation of logical processes including cardiovascular function, bowel motility, ejaculatory latency, and bladder control, hemostasis, heart rate, intestinal motility, cell growth in liver, bone, and pulmonary arteries, and the development of heart, brain, and mammary gland and some addition roles in immunoregulatory functions including pro-inflammatory functions (Berger, 2009). Pro-inflammatory feature is now known that platelets ensure the targeted release of serotonin in platelet-activating environments like a thrombus or an inflammatory reaction (Wagner, 2008;Endo, 1997;Mössner, 1998).
Contrary to what has been said about the anti-inflammatory properties of serotonin, a specific activation of the 5-HT2A receptor subtype in primary aortic smooth muscle cells causes a superpotent inhibition of tumor necrosis factor (TNF)-α-mediated inflammation (Yu, 2008;Herr, 2017).
Possible sources for peripheral serotonin are plasma, monocytes/macrophages, lymphocytes, vascular smooth muscle cells, adipocytes, mast cells (although human mast cells were long thought not to contain serotonin), and platelets (Herr, 2017). Nanomaterials possess unique features which make them particularly attractive for biosensing applications.
Carbone nanotubes based on the number of walls, designed as single-walled carbon nanotube and multiwalled carbon nanotube. The side-walls of these tubes are made up of a hexagonal plexus, of carbon atoms, similar to graphene and are usually capped at both ends by one half of a fullerene-like molecule (Zhu, 2002;Tîlmaciu, 2015). Carbon nanotubes (CNTs) can be used as scaffolds for immobilization of biomolecules at their surface and best suited materials for the transduction of signals associated with the recognition of analytes, metabolites, or disease biomarkers due to their several exceptional properties such as physical, chemical, electrical, and optical characteristics properties. Besides CNTs can cross biological barriers including the cell membrane (Tîlmaciu, 2015;Pantarotto, 2004;Monajjemi,2019).

Material and Methods
Quantum mechanics (MQ)Calculations were performed using Gaussian 09 to study chemical and physical properties of nuclei (Reed, 1988;. In this work, it has been mainly focused on optimized structures of combined Dopamine and Serotonin molecule with SWNTs with 7.0, 7.5, 7,7 and 10.0 nanometer diameter in NMR, POP=MK (Merz-Singh-Kollman) and freq methods.
Gaussian 09 uses numerical methods to find solutions to wave functions. Varies methods such as molecular orbital energies, bond energies, molecular geometries and energies, and vibrational frequencies, along with many other properties are appreciable by this program (Joohari, 2015;Naghsh, 2018;. Nuclear magnetic resonance (NMR) typically utilizes a tuned resonance circuit with impedance matching to transmit power and receive signal (Hopper, 2011;Le, 2020;. Parameters optimized in NMR including magnetic isotropic (σiso) and magnetic anisotropic (σaniso) shielding, σ11,σ22,σ33, atomic charges, asymmetry parameter (η), chemical shift anisotropy (Δσ ) and span (Ω) as shown in the following result for its fundamental importance in chemistry and biochemistry studies (Facelli, 2002), in which calculated in GIAO magnetic shielding for Dopamine and Serotonin by using B3LYP method with 6-31G(d) basis set which gathered in table 1-2.
Quantum chemistry calculations have been fulfilled to determine the partial charges on atoms. For this purpose, the Merz-Kollman-Singh (MK) algorithm (Singh, 1984;Menegon, 2002;Bultinck, 2002; was used, because of the fact, that MK charges are derived from the electrostatic potential, they are known to be much less basis dependent in comparison with the Mulliken charges.
Frequency methods with uff/6-31 G basis set has also been assessed by zero-point energy correction, enthalpy, and Gibbs free energy presented in table 3. The ideas of quantum zero-point energy may be used to measure forces arising in electromagnetism, nuclear physics, and pair theory (HBoyer, 2011;.

RESULT AND DISCUSSIONR
In this work the NMR parameters as Ab initio calculation of nuclear magnetic shielding such as σiso (isotropy shielding) and σaniso (anisotropy shielding), asymmetry parameter (η), chemical shift anisotropy (Δσ) and span (Ω) for some of the carbon atoms in Dopamine and Serotonin-SWCNT complex have been theoretically studied. the magnetic properties of atomic nuclei and physical and chemical properties of atoms have shown in table 1-2.
According to table 1, in complex Dopamine+7.0 (nm) diameter SWCNT the most value of σiso belongs to C111 (132.6) and C1 has the most value of σaniso (431.1) and Ω (712.7), the most parameters of Δσ are positive and the maximum specified in C25(318.7) .C54 has the maximum amount of η (7.004), while The most content of etta (η) are negative.
For Dopamine+SWCNT (7.5 nm diameter) most positive results described below: Maximum extent of σiso and σaniso shown in C54(130.2) and C1(188.05) and most values of Δσ, η and Ω respectively belong to C41(180.4), C81(1.46) and C15(205.9). C7 in Dopamine combined 7.7 (nm) SWCNT has the two-minimum value of σiso and σaniso and the maximum amount of these two parameters respectively specified for C81(148.1) and C71 (165.4). Among positive values of Δσ and Ω, most value is for C23(125.5) and for C7(184.5) and C1 has the most amount of η (5.3) and in the end of table 1, for medication connected to 10.0(nm)SWCNT C98 has the two maximum value of σiso and σaniso (2345.7 and 6599.9) and also C7 has the two maximum value of Δσ and Ω (5109.2 and 10365.9) and minimum value of σiso (-3276.8). The Δσ parameter of NMR for carbon atoms in dopamine are shown in Fig.1.  Table 2. comparison of NMR chemical shielding tensors data calculated by B3LYP models with 6-31G (d) basis set for C atoms in Serotonin with 7.0,7.5,7.7,10.0 (nm)diameters SWCNT As it shown in table 2, in Serotonin +7.0 (nm) SWCNT complex, C1 has the most value of σiso (116.4) and the most value of σaniso, Δσ and Ω demonstrated in C78 which respectively equals with 533.07,329.9 and 787.1 and C65 has the most value of η (42.3). In Serotonin+7.5 nm diameter SWCNT complex, the maximum level of σiso and σaniso respectively belongs to C87(129.5) and C1(188.1) and the minimum level belongs to C49(109.5) and C65(149.8) and also the maximum level of Δσ and Ω are respectively 187.5 and 242.5 which belongs to C57 and C42. Most of the etta (η) parameters have been reported positive and the maximum value belongs to C81 (8.2). C1 in drug+7.7(nm)diameter SWCNT has the two maximum and minimum value of σiso (160.01) and σaniso (104.7) and the minimum value of σiso (135.3) and maximum value of Ω (242.5) also belongs to C7. As it specified in these results, the most value of σaniso, Δσ and η are for C65(165.6), C27(152.8) and C32(1.58). C7 in Serotonin connected to SWCNT (10.0nm diameter) has the most value of σiso (870.3) , σaniso(2098.6) and Ω(2136.5) . Most of the Δσ and etta (η) parameters have been reported negative and the maximum values belong to C94 (1005.4) and C32(0.9). The ƞ parameter of NMR for carbon atoms in serotonin are shown in Fig.2. Fig.2. ƞ parameter of NMR; calculated by B3LYP models with 6-31G (d) basis set for C atoms in Serotonin with 7.0,7.5,7.7,10.0 (nm)diameters SWCNT Thermodynamic paraeters including zero-point energy, total energy, enthalpies (ΔH) and Gibbs free energy (ΔG) of the complex were computed by Freq method using Uff/6-31G(d) obtained and summarized in table3. Also, we can comparison atom charge distributions in MK method for the two-molecule complex in table 4-5.

4.CONCLUSION
In this work, we theoretically investigated the structure features of Dopamine and Serotonin as a biological active compound and single-walled carbon nanotube as a biological transfer. Chemical shift anisotropy asymmetry (η), isotropy (σ iso), anisotropy (σ aniso), Δσ, K and chemical shift tensor (δ) were calculated based on theoretical data obtained from BL3Y/6-31G(d) levels of theory. Moreover, thermodynamic analyses with uff/6-31 G basis set were performed and then stabilization energies such as Zero-point energy, total correction, enthalpy and free Gibs energy and also Merz-Kollman Singh (MK) analysis carried out by gaussian 09 application.