untitled ISSN 2 Density compou Zarife Sibe 1 Sinop University 2 Yeditepe Univer * Corresponding Tel.: +90.546.407 ARTICLE INF DOI: 10.5155/eu Received: 01 Dec Received in revis Accepted: 25 De Published online Printed: 31 Marc KEYWORDS Indole Piperazine DFT calculations Crystal structure Frontier molecu Molecular electr 1. Introducti The class subtypes, ter receptor is p the receptor s σ1 ligands. T membrane‐sp cloned from and human [ interest for e ressants [10 agents [14‐1 antagonists m several patho cocaine abuse dystonic reac cancer and tu Many imp systems can computationa computer ha describe the computationa 2153‐2249 (Prin functiona nd 1‐{3‐[ el Şahin 1,*, M y, Faculty of Engine rsity, Faculty of Pha author at: Sinop U 77397. Fax: +90.368 FORMATION urjchem.8.1.1-7.15 cember 2016 sed form: 22 Decem cember 2016 e: 31 March 2017 ch 2017   s e ular orbitals rostatic potential m ion s of σ receptor rmed as σ1 an pharmacologica sequence inform The 223‐amino panning region several species 3‐7]. Ligands in example as atyp ], anti‐cocaine 17]. Thus, sele may be potenti ologic conditio e, memory and ctions induced umor diagnosis. portant physioc be predicted al techniques rdware and so chemical pro al techniques [1 t) / ISSN 2153‐2 Europ al comput 4‐(4‐fluo Mine Yarım 2 eering and Architec armacy, Departmen University, Faculty o 8.2714152. E‐mail 512 mber 2016 map rs is subdivide nd σ2 receptor ally well charac mation and ava acid σ1 recep ns [1,2] has s, including mo nteracting with pical antipsych e agents [11‐1 ective σ1 and ially useful dru ons such as ps learning disord by classical a chemical proper from first pri [18]. With r oftware, it is p operties of mo 19]. European Journ Europe 2257 (Online)  2 http://dx.doi.org pean Jo Journal web tational an rophenyl 2 and Meriç ctures, Department nt of Pharmaceutic of Engineering and address: zarifesibe ABSTRACT The crystal an indole (I) has compound I in (DFT) with B3 addition, densi map, frontier chemical reacti Cite this: Eur. J ed into at least rs. To date, th cterized becau ailability of sele tor with two t been purified ouse, rat, guine h σ receptors a otics [8,9], ant 13], and antitu d σ2 agonists ugs for treatme ychiatric disor ders, dyskinesia antipsychotic d rties of the chem inciples by va ecent advance ossible to corr olecules by va nal of Chemistry ean Journal of Ch 2017 Atlanta Pub g/10.5155/eurjche ournal bpage: www. nd X‐ray )piperazi Köksal 2 t of Energy Systems cal Chemistry, 3475 Architectures, Dep el@sinop.edu.tr (Z.S nd molecular str been determine n the ground sta 3LYP/6‐31G(d,p ity functional ca molecular orbi ivity descriptors J. Chem. 2017, 8( t two he σ1 se of ective trans‐ and ea pig are of tidep‐ umor and ent of rders, a and drugs, mical arious es in rectly arious D calcu case agre pred stru ioniz path I sigm indo In s logra have mole yl]pr been dens elect mole reac 31G 8 (1) (2017) 1‐7 hemistry lishing House LLC em.8.1.1-7.1512 of Che eurjchem.com studies o in‐1‐yl]pr s Engineering, 5700 55, Kayışdağı, İstan partment of Energy S. Şahin). ructure of 1‐{3‐ ed by single‐cry ate has been ca p) basis set and alculations of th itals, atomic ch s of compound I (1), 1‐7 Density functio ulations in theo es the results o eed quite sati dicts a great v ctures, vibrati zation energies hs, etc. In order to inv ma (σ) receptor ole scaffolds we pide of its imp aphy and theo e not been inve ecular structur ropyl}‐1H‐indo n determined b sity functional trostatic poten ecular orbitals ctivity descripto (d,p) level of th 7 C ‐ All rights rese emistry m n pharma ropyl}‐1H 00, Sinop, Turkey bul, Turkey Systems Engineeri [4‐(4‐fluorophe ystal X‐ray diffr alculated using t d compared wi he structure, mo harges, thermod were performed onal theory (DF oretical modeli of DFT calculat isfactorily wit variety of mole ional frequenc s, electric and m vestigate the m rs binding, a se ere already syn portance, men oretical calculat estigated so far. re of 1‐{3‐[4‐ ole (I), one of by single‐crysta calculations o ntial, thermod s, atomic cha ors have been heory. rved ‐ Printed in y aceutical H‐indole ing, 57000, Sinop, T nyl)piperazin‐1 action. Molecula the density func ith the experim olecular electro dynamic functio d. FT) has been ve ing since the 19 tions for solid‐ h experimenta ecular properti cies, atomizat magnetic prope olecular featur eries of compou nthesized and d tioned above, tions of the ti In this work, t (4‐fluoropheny the those com al X‐ray diffrac of the structu dynamic funct arges and glo performed at the USA Turkey. ‐yl]propyl}‐1H‐ ar geometry of ctional method mental data. In static potential ons and global ry popular for 970s. In many ‐state systems al data. DFT ies: molecular tion energies, erties, reaction es involved in unds based on discussed [20]. X‐ray crystal‐ tle compound the crystal and yl)piperazin‐1‐ mpounds, has ction. Besides, ure: molecular ions, frontier obal chemical the B3LYP/6‐ 2 Şahin et al. / European Journal of Chemistry 8 (1) (2017) 1‐7 Table 1. Crystal data and structure refinement for compound I. Empirical formula C21H24FN3 Formula weight 337.43 Temperature/K 296 Crystal system Monoclinic Space group P21/c a/Å 17.6087(11) b/Å 5.9840(2) c/Å 21.6813(16) α/° 90.00 β/° 126.496(4) γ/° 90.00 Volume/Å3 1836.56(19) Z 4 ρcalcg/cm3 1.220 μ/mm‐1 0.080 F(000) 720.0 Crystal size/mm3 0.640 × 0.480 × 0.260 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 2.88 to 52 Index ranges ‐21 ≤ h ≤ 21, ‐7 ≤ k ≤ 7, ‐23 ≤ l ≤ 26 Reflections collected 12542 Independent reflections 3619 [Rint = 0.0425] Data/restraints/parameters 3619/2/227 Goodness‐of‐fit on F2 0.898 Final R indexes [I≥2σ (I)] R1 = 0.0447, wR2 = 0.1004 Final R indexes [all data] R1 = 0.1072, wR2 = 0.1182 Largest diff. peak/hole / e Å‐3 0.09/‐0.10 2. Experimental 2.1. Synthesis of 1‐{3‐[4‐(4‐fluorophenyl)piperazin‐1‐yl] propyl}‐1H‐indole (I) To a solution of 4‐fluorophenyl piperazine (5 mmol) in 10 mL of acetone was added 7.5 mL of a 25% solution sodium hydroxide. 30 minutes later, 1‐bromo‐3‐chloropropane (5.5 mmol) was added carefully to minimize its mixing with aqueous layer. The mixture was stirred slowly for 22 h with a magnetic stirrer. The organic phase was then separated and the solvent was removed under vacuum. A mixture of indole (2.5 mmol) and 87% w:v solution KOH (7.5 mmol) in DMSO (30 mL) was stirred at room temp. for 1 h. Reaction mixture was cooled in ice‐water bath to 0 °C and 1‐(3‐Chloropropyl)‐4‐ (4‐fluorophenyl)piperazine in DMSO (10 mL) was added dropwise. The stirring was continued at room temperature for 20‐30 h. After addition of water (50 mL) and extraction with Et2O, the organic layer was washed with water and dried over anhydrous Na2SO4. The solvent was evaporated and the oily residue was purified by column chromatography (SiO2, AcOEt : n‐hexane, 1:2) to give 1‐{3‐[4‐(substituted phenyl)piperazin‐1‐ yl]propyl}‐1H‐indole as an oil. These data about the compound were published in elsewhere [20]. Color: Colorless. Yield: 18%. FT‐IR (KBr, , cm‐1): 3022‐2763 (C‐H), 1245 (C=C). 1H NMR (400 MHz, CDCl3, δ, ppm): 6.86‐7.64 (m, 10H, indole + phenyl), 4.24 (t, 2H, indole N‐CH2‐CH2‐CH2), 3.13 (t,4H, piperazine H3, H5), 2.57 (t, 4H, piperazine H2, H6), 2.33 (t, 2H, CH2‐CH2‐CH2‐N piperazine), 2.03 (q, 2H, CH2‐CH2‐CH2). 13C NMR (100 MHz, CDCl3, δ, ppm): 158.79, 155.45, 148.62, 136.40, 129.31, 128.73, 121.57, 119.49, 117.70, 117.64, 116.01, 115.79, 110,43, 101.13 (aromatics), 55,13 (indoleN‐CH2‐CH2‐CH2), 55.14 (piperazine C3, C5), 49.65 (piperazine C2, C6), 43.95 (CH2‐CH2‐CH2‐N piperazine), 27,67 (CH2‐CH2‐CH2). Anal. calcd. for C21H24FN3: C, 74.75; H, 7.17; N, 12.45. Found: C, 74.71; H, 7.13; N, 12.46%. 2.2. Crystallography Colorless single‐crystal of compound I suitable for data collection were selected and performed on a STOE IPDS II diffractometer with graphite monochromated MoKα radiation λ = 0.71073 Å. The structures were solved by direct‐methods using SHELXS‐97 [21] and refined by full‐matrix least‐squares methods on F2 using SHELXL‐97 [21] from within the WINGX [22,23] suite of software. The parameters for data collection and structure refinement of compound I are listed in Table 1. All non‐hydrogen atoms were refined with anisotropic parameters. Hydrogen atoms bonded to carbon were placed in calculated positions (C–H = 0.93‐0.97 Å) and treated using a riding model with U = 1.2 times the U value of the parent atom for CH and CH2. Molecular diagrams were created using MERCURY [24]. Geometric calculations were performed with PLATON [25]. Details of hydrogen‐bond dimensions are given in Table 1. 2.3. Theoretical methods All theoretical computations were done by using Gaussian 03 software package [26] and Gauss‐view visualization program [27]. The compound I was optimized by using DFT method [28,29]. The initial guess of the compound was first obtained from the X‐ray coordinates. DFT calculations with a hybrid functional B3LYP (Becke’s three parameter hybrid functional using the LYP correlation functional) at 6‐31G(d,p) basis set using the Berny method [30,31] were performed. To investigate the reactive sites of the compound I, the molecular electrostatic potentials were calculated using the same method. Additionally, we carried out calculations in four kinds of solvent (water, benzene, ethanol, and chloroform) in order to evaluate the solvent effect to total energy, HOMO and LUMO energies, dipole moment and chemical reactivity descriptors of the title compound. The computations were done with the B3LYP/6‐31G(d,p) level using PCM model. 3. Results and discussion 3.1. Description of the crystal structure The molecular structure of compound I was determined by X‐ray crystallography have been depicted in Figure 1. The compound crystallizes in the space group P21/c with Z = 4 and. The molecule is not planar. The compound contains a phenyl ring, a piperazine ring and a indole ring. The phenyl and indole rings are approximately planar and the dihedral angle of between these planes is 1.47°. The respective maximum deviations from the least‐squares planes being 0.0091(14) Å for atom C16 and 0.0012(13) Å for atom N1. The piperazine ring exhibits a puckered conformation, with puckering parameters [32] q2 = 0.0817(22) Å, q3 = ‐0.5393(24) Å, QT = 0.5457(24) Å, ϕ = 178.2(18)° and θ = ‐171.26(23)°, which indicates that the piperazine ring has a chair conformation. Table 2. Selecte Bond lengths (Å C1–C6 C7–C8 C7–C6 N2–C12 N2–C15 N3–C14 N3–C13 N1–C1 N1–C8 N1–C9 N2–C11 N3–C16 F1–C19 Bond angles (°) C9–C10–C11 C16–N3–C14 Table 3. Hydrog D–H···A C7‐H7···Cg4 i C13‐H13B···Cg3 * Symmetry cod The selec are given in similar to the distances in t the expected piperazine an Molecules framework b molecule at centroid Cg4 parallel to th hydrogen‐bon C(10) chain combination edge‐fused R4 3.2. Optimize The geom B3LYP/6‐31G together with ed bond lengths and Å) ) gen‐bond paramet ii es: (i) ‐1/2+x, 1/2‐ cted bond lengt Table 2. The C e corresponding the piperazine d single bond nd indole deriva s of compound y C–H···π inter (x, y, z) acts 4i ring, so form he [101] directi nd donor to th running para of the C(13) an 44(32) rings (Fi ed geometry metric parame G(d,p) level by h correspondin Şahin et a d angles (Å, °). ters (Å, °) *. D–H 0.93 0.98 ‐y, ‐z; (ii) ½+x, 3/2 Figure 1. ths, bond angles C19–F1 bond le g bond lengths and indole rin d lengths, as atives [34,35]. I are linked to a ractions (Table as hydrogen‐b ming a C(13) ion. Similarly, a e centroid Cg3 allel to the [1 d C(10) chains gure 2). ters of I were DFT method an ng experimenta al. / European Jou Experimen 1.405(3) 1.344(3) 1.359(2) 1.418(3) 1.456(2) 1.450(2) 1.459(2) 1.376(2) 1.371(2) 1.454(2) 1.455(3) 1.408(2) 1.360(3) 113.3(2) 117.4(2) 2‐y, ½+z; Cg3: C1–C Ex The . The molecule of c s and torsion a ength is 1.360( [33]. The C–N ngs (Table 2) a reported in o a three‐dimens 3). Atom C7 in bond donor to chain [36] run atom C13 serv ii ring, so form 101] direction. generates a cha e calculated at nd listed in Tab al values. As ca urnal of Chemist ntal (X‐ray) H···A 3.0366 2.9845 C6 ring Cg4: C16–C xperimental (X‐ra oretical (DFT/B3 compound I showin ngles (3) Å, bond are as other sional n the o the nning ves as ming a The ain of t the ble 2, an be seen expe bond supe (blac RMS resu repr betw can were whe the c 3.3. chem T high part invo try 8 (1) (2017) 1 D···A 3.83 3.91 C21 ring. ay) 3LYP) ng the atom labelin n in Table 2, th erimental value d lengths is erimposition o ck) and its DF SE of 0.332 Å ult, it may be c roduce the geom ween the calcul be attributed t e carried out w ereas the exper crystalline state Frontier molec mical reactivity The lowest uno hest occupied ticular interest olved in chemica 1‐7 Theoretical (DF 1.424 1.370 1.435 1.463 1.463 1.458 1.467 1.384 1.385 1.455 1.465 1.416 1.352 113.7 117.7 A 36 (2) 10 (2) ng scheme. he bond length es. The bigges 0.078 Å for f the X‐ray st FT (red) optim was given in concluded that metry of compo lated and obser to the fact that with isolated mo imental values e. cular orbitals ( y in solvent me occupied molec molecular orb as these are t al reactions [37 T/B3LYP) D–H···A 144.98 159.87 s are extremel st deviation of C7–C6 bond. tructure of the mized counterp Figure 3. Acco the B3LYP cal ound I. The sm rved geometric t the theoretica olecules in the g were based on (FMOs), total e edia cular orbital (L bital (HOMO) the orbitals mo 7]. 3 ly close to the f the selected Furthermore, e compound I part, giving a ording to this culations well mall differences cal parameters al calculations gaseous phase n molecules in energies and UMO) and the are often of ost commonly 4 Table 4. Calcula Etotal (Hartree) EHOMO (eV) ELUMO (eV) ΔE (eV) D (Debye)  (eV) S (eV‐1) μ (eV) χ (eV) ω (eV) F Figure The HOM such propert molecule to a energy levels B3LYP/6‐31G Figure 4, the ring where th ated energies, dipo Gas pha ‐1078.80 ‐0.19486 ‐0.00883 0.18603 1.9892 0.09302 10.7504 ‐0.10183 0.10183 0.05576 Figure 3. Atom‐by‐ e 4. Molecular orb MO and LUMO a ties as molecul absorb light. Fig of the HOMO a G(d,p) level for HOMOs are ma he LUMOs are p le moments, fronti ase (ε=1) 025 6 3 4 3 6 Figure 2. Crys ‐atom superimposi ital surfaces and e are also impor lar reactivity a gure 4 shows th and LUMO orbit r compound I. ainly localized o opulated on the Şahin et al. / Eu ier orbital energies Benzene (ε=2 ‐1078.8081 ‐0.19561 ‐0.00737 0.18824 2.2604 0.09412 10.6247 ‐0.10149 0.10149 0.05472 stal structure of com ition of the calcula nergy levels for th tant in determ and the ability he distributions tals computed a As can be see on the around in e phenyl ring. uropean Journal o s and chemical rea 2.3) C ‐ ‐ ‐ ‐ mpound I, showing ated structure (red e HOMO and LUMO mining of a s and at the en in ndole W (ben effec mom com 31G Tabl of Chemistry 8 (1 activity descriptors Chloroform (ε=4. ‐1078.8122 ‐0.19659 ‐0.00695 0.18964 2.4462 0.09482 10.5463 ‐0.10177 0.10177 0.05461 g the formation of ) over the X‐ray st O of the title comp We carried ou nzene, ethanol, ct to the total ment and che mpound. The co (d,p) level usin le 4. 1) (2017) 1‐7 s. .9) a R42(32) rings. ructure (black) for ound computed at ut calculations chloroform) in energy, HOMO mical reactivit omputations we ng PCM model Ethanol (ε=24.5 ‐1078.8161 ‐0.19746 ‐0.00727 0.19019 2.6268 0.09510 10.5158 ‐0.10237 0.10237 0.05594 r the title compoun t B3LYP/6‐31G(d,p in three kin order to evalua O and LUMO en ty descriptors ere done with and the result 5) nd. p) level. ds of solvent ate the solvent nergies, dipole of the title the B3LYP/6‐ ts are given in Table 5. Calcula Atom C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C11 C12 C13 The elect derivative of electrons, wh average of th (EA). Except definition of e The seco number of el called the sof term of the io η The elect attract electro These con softness of m LUMO gap, an stability and unfavorable t electrons fro related to th indicates a so large contribu of how easily fields [38]. As can b HOMO‐LUMO the stability polarity of the ated net charges by M 0 ‐ ‐ ‐ ‐ 0 ‐ 0 ‐ ‐ ‐ ‐ ‐ Figure tronic chemica f the energy hich in a finite he ionization p for a differenc electronegativit nd derivative o ectrons is hard ftness (S)), whi onization potent IP EA trophilicity, wh ons, is defined a ncepts play an i molecules. A ha nd a large HOM low chemical to add electron om low‐lying H he HOMO‐LUMO oft molecule an ution to the po y the electron d een seen in T O energy gaps, of the molecu e solvent. Şahin et a y Mulliken populat Mulliken charges 0.370407 0.141493 0.085580 0.101664 0.097919 0.280416 0.080853 0.580953 0.023377 0.192327 0.011916 0.025349 0.021697 5. Molecular electr l potential µ is with respect difference ver potential (IP) a e in sign, this i ty χ [38]. of the energy w dness η (the inv ich again may tial and electro hich measures as following important role ard molecule h MO‐LUMO gap l reactivity, as n to a high‐lyin HOMO [39]. Po O gap. A smal nd a small ene olarizability. So ensity can be d able 4, we can the hardness, ule increase w al. / European Jou tion method. rostatic potential m s given as the to the numbe sion is given a and electron af is also the Mul with respect to verse quantity be approximat n affinity [38]. the total abili in the hardnes has a large HO implies high ki s it is energet ng LUMO, to ex olarizability is l HOMO‐LUMO ergy gap will g oftness is a mea distorted by ext n conclude tha dipole moment with the incre urnal of Chemist Atom C14 C15 C16 C17 C18 C19 C20 C21 F1 N1 N2 N3 map of compound first er of as the ffinity lliken (1) o the η‐1 is ted in (2) ity to (3) s and OMO‐ inetic ically xtract also O gap give a asure ternal at the t and asing 3.4. M used nucl inter char pote dista expe inve pote meth elect nucl well of on subs that seen the phen elect havi 3.5. I Müll dete acid syste liste that char char char try 8 (1) (2017) 1 m I calculated at DFT Molecular elec Molecular elec d for the qual leophilic reac ract‐tions betw rges [41] and d ential in the m ance from a m eriences a cert estigate the rea entials were hod. The negat trophilic react leophilic reactiv l suited for ana ne molecule by strate interacti the two specie n in Figure 5, t indole and ph nyl and indole trophilic reacti ing high electro Mulliken popu In addition to liken populatio ermination of m ity‐basicity beh em. The Müllike ed in Table 5 an all nitrogen rge. The N3 a rges, while the rges. 1‐7 Mulli ‐0.02 ‐0.02 0.338 ‐0.08 ‐0.09 0.326 ‐0.09 ‐0.09 ‐0.31 ‐0.55 ‐0.48 ‐0.57 T/B3LYP/6‐31G(d, ctrostatic poten ctrostatic poten litative interpr ctions [40], ween polar spec define regions o molecule [42]. molecule at w tain amount of active sites of I evaluated usi tive (red) regio tivity and the vity. The electr lyzing processe y another, as in ons, because it es first “see” eac he red regions enyl rings. Acc rings are the m ion and they c ophilic attractio ulation analysis molecular ele on analysis pla molecular polari havior and a lo en atomic charg nd graphically atoms and flu atom (‐0.57585 C8 (0.580953) iken charges 0510 2341 8599 8027 6745 6612 6125 0987 4963 0398 0526 5855 , p) level. ntial ntial (MEP) m etation of elec rationalize i cies, the calcula of local negativ This surface r hich a positiv f attraction or I the molecula ing the B3LY ons of MEP w positive (blue rostatic potenti es based on the n drug‐receptor t is through th ch other [43‐45 s are chiefly co cording to thes most suitable r can easily reac n such as metal s ctrostatic pote ay an importan izability, electro ot of properties ges of the title c shown in Figur uorine atom h 55) has the m ) atom has the 5 aps are often ctrophilic and ntermolecular ation of atomic e and positive represents the ve test charge repulsion. To r electrostatic YP/6‐31G(d,p) ere related to e) regions to ial V(r) is also e “recognition” r, and enzyme‐ heir potentials 5]. As it can be ncentrated on se results, the regions for the ct with atoms l atoms. ential analysis, nt role in the onic structure, s of molecular compound are re 6. It is seen have negative most negative most positive 6 Table 6. Thermo Temperature (K H (kcal/mol) C (cal/mol.K) S (cal/mol.K) EThermal(kcal/mo Figu 3.6. Thermod Thermod understandin calculations thermodynam experimental or impossible The entro following [46 ln √ ∑ where rotational a respectively. atom number Boltzmann co constant (6.6 pressure, moment of in The abso energy (G) of and the speci odynamic properti K) l) ure 6. Calculated n dynamic prope ynamic prop ng and design also enable p mic properties l data, or for w e to obtain [37]. opy (S) and hea 6‐48] / / / ln exp ∑ , , and and vibrationa R is the gas co r in a molecule onstant (1.380 6260755×10‐34 J is the symme nertia and is th lute internal en f the molecule fied temperatu ies of the title com 100 2.09 29.8 94.9 253 net charges by Mul erties erties are t n of chemica predictions to of systems for which experime . at capacity (C) a / / , , al entropy an nstant (8.3145 e, m is the mole 0658×10‐23 J/K) J.s), T is the te etry number fo he vibrational fr nergy (U), enth are calculated re (T) [46‐48] Şahin et al. / Eu mpound at different 0 996 8331 9174 3.384 liken population m the key in al processes. be made of r which there ntal data is dif are calculated a are translati nd heat cap 51 J/mol·K), N i ecular mass, k i ), h is the Pla emperature, p i or rotation, I i frequency. halpy (H) and G as following a uropean Journal o t temperatures. 200 6.4446 56.0084 124.066 257.536 method plots for th the DFT f the is no fficult as the (4) (5) (6) ional, acity, is the is the anck’s is the s the Gibbs t 0 K (7) (8) (9) (10) whe and of m temp O from leve heat ≤ 50 6. In inter scali [49,5 dete A capa temp the temp atom atom T pert quad for t corr H = 0 C = 2 S = 6 T para used to re to sy 4. Co I [4‐(4 of Chemistry 8 (1 300 13.4229 82.1173 151.973 264.322 he title compound ( ere is the in is the zero poi are the th molecular transl perature, respe On the basis of m density func l, the statistica t capacities (C), 00) for the title n the calculatio racting particle ing factor for 50], which is ermining the the As seen in Tab acities, entropie peratures rang molecular vib peratures. As th ms in the lattic ms and molecul The correlation ties Cop,m, Som a dratic formulas these thermody relation equatio 0.54098+0.002 2.739+0.25463 68.4434+0.3047 The results ca ameters for unk d to compute th elationships of ynthesize simila onclusions In this study, t 4‐fluorophenyl) 1) (2017) 1‐7 400 23.2463 110.123 180.044 273.955 (Hydrogen atoms a nternal energy int energy of th hermal energy c ation, rotation ectively. f theoretical ha ctional calcula al standard the , entropies (S) e compound we ons, the ideal g es of the reactio the vibrational s used for a ermodynamic f ble 6, we can es and enthalpy ging from 100 t brational inten he temperature ce increases. Vi es in the lattice n equations be and Hom and t s and the corre ynamic propert ons of the title c 233T+1.4156×1 T+4.5207×10‐5 74T–2.0342×10 an be used t known data in he other thermo thermodynami ar molecules in he crystal and )piperazin‐1‐yl 500 35.70 134. 204.7 286.2 are omitted for cla due to electron he molecule at 0 corrections due and vibration a rmonic frequen ations at B3LY ermodynamic f and enthalpy (H ere obtained an gas approxima on systems are l frequencies i an accurate p functions. see that the s y changes are in to 500 K due to nsities are inc e increases, the ibrational moti e to be less well etween thermo temperatures w esponding fittin ties are all beyo ompound are a 0‐4T2 r2 = 0.999 T2 r2 = 0.987 0‐6T2 r2 = 0.9999 o calculate th further studies odynamic energ ic functions and further studies molecular stru l]propyl}‐1H‐in 065 508 741 223 rity). nic motion and 0 K. , e to the effects at the specified ncies obtained YP/6‐31G(d,p) functions, viz., H) (100 ≤ T/K nd listed Table tion and non‐ assumed. The is also 0.9627 prediction in standard heat ncreasing with o the fact that creasing with entropy of the ons cause the ordered. odynamic pro‐ were fitted by ng factors (R2) ond 0.999. The as follows: 99 (11) 9 (12) 9 (13) hermodynamic s. They can be gies according d be beneficial s. ucture of 1‐{3‐ dole (I) has Şahin et al. / European Journal of Chemistry 8 (1) (2017) 1‐7 7 been determined by single‐crystal X‐ray diffraction. Molecules of compound I are linked to a three‐dimensional framework by C–H···π interactions. Molecular geometry of compound I in the ground state has been calculated using the density functional method (DFT) with B3LYP/6‐31G(d,p) basis set and compared with the experimental data. Despite the differences observed in the geometric parameters, the general agreement is good and theoretical calculations support the solid‐state structure. In addition, HOMO and LUMO orbitals computed at the B3LYP/6‐31G(d,p) level for compound I. It is seen that the HOMOs are mainly localized on the around indole ring where the LUMOs are populated on the phenyl ring. We carried out calculations in three kinds of solvent (benzene, ethanol, chloroform) in order to evaluate the solvent effect to the total energy, HOMO and LUMO energies, dipole moment and chemical reactivity descriptors of the title compound and it is seen that the HOMO‐LUMO energy gaps, the hardness, dipole moment and the stability of the molecule increase with the increasing polarity of the solvent. According to MEP map of the molecule, the phenyl and indole rings are the most suitable regions for the electrophilic reaction and they can easily react with atoms having high electrophilic attraction such as metal atoms. Besides, on the basis of theoretical harmonic frequencies obtained from density functional calculations at B3LYP/6‐31G(d,p) level, the statistical standard thermos‐ dynamic functions, viz., heat capacities (C), entropies (S) and enthalpy (H) (100 ≤ T/K ≤ 500) for the title compound were obtained and it is seen that the standard heat capacities, entropies and enthalpy changes are increasing with temperatures ranging from 100 to 500 K due to the fact that the molecular vibrational intensities are increasing with temperatures. We hope the results of this study will help researchers to design and synthesis new materials. Acknowledgement We sincerely thank to Professor Şamil Işık for his help with the data collection. Supplementary data Crystallographic data for the structure reported in this article have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number 1037165. 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