Experimental Spectroscopic (FT-IR, 1H and 13C NMR, ESI-MS, UV) Analysis, Single Crystal X-Ray, Computational, Hirshfeld Analysis, and Molecular Docking of 2-Amino-N-Cyclopropyl-5-Heptylthiophene-3-Carboxamide and Its Derivatives

Abstract Amino-N-cyclopropyl-5-heptylthiophene-3-carboxamide (ACPHTC) and its functional derivatives were synthesized and analyzed via single-crystal X-ray diffraction at 296 K, 1H,13C NMR, UV–Vis, FT-IR, and ESI-MS spectral analysis. ACPHTC crystallizes in a tetragonal crystal system, space group I-4 with Z = 16 and the following unit cell dimensions: a = 19.2919(4) Å, b = 19.2919(4) Å, c = 17.1515(5) Å. Using HF and DFT, B3LYP methods with the 6-311++G(d,p) basis established by the GAUSSIAN 16 program, the optimized molecular geometric parametersof ACPHTC and its derivatives were computed. The ACPHTC molecule hyper conjugative interactions are revealed by the NBO analysis, which has been carried out. Electrophilic and nucleophilic sites have been identified throughMEP. The first-order hyperpolarizability, dipole moment, and polarizability of the ACPHTC were taken into account when analyzing its NLO behavior. Additionally, the energies of ACPHTC HOMO and LUMO were found. The TD-DFT has been used to determine the UV-Vis spectra and electronic features such as frontier orbitals and band gap energies. The GIAO method was used to determine the 1H and 13C NMR chemical shifts of ACPHTC molecule and compare them to experimental results. Fingerprint plots,Hirshfeld surface are used to evaluate the properties of intermolecular interactions. Finally, docking studies were used to examine the binding affinity,of ACPHTC and its derivatives.


Introduction
Multicomponent reactions (MCRs) have acquired a lot of attraction among synthetic chemists because of their ease of use, selective creation of target compounds, cost-effectiveness, and reduced waste production. 1 MCRs have substantially increased their reach, from basic three-component reactions 2 to more sophisticated processes involving a larger range of reactants, 3 leading in the development of target molecules 4 and compound libraries 5 with a diversity of biological 6,7 and industrial features. Taking use of the traits currently existing in the MCR product, which allow new reactants to engage in the process, 8 is one essential strategy to increase an MCR's ability to deliver complex products. Sulfur heterocycles have been studied for their wide range of activities in drug development because of the availability of unshared pairs of electrons and electronegativity variations in conjunction with cyclic chemical structures. Thiophene; is a simple sulfur heterocycle with five members that are mostly found in natural products and physiologically active compounds. Thiophene substituents are mostly employed in the disciplines of material science (like developments of semiconductor polymer and light-emitting diode), life sciences, and pharmaceutical sciences. 9 The 3-components Gewald method 10 that generates 2-aminothiophenes with reactive adjacent NH 2 and CN functional groups for possible use in more cycling reactions using a-methylene bearing ketones, dicyanomethane, and S 8 , is a good place to start evaluating this approach. Because MCRs are being used increasingly often in synthesis, we are looking at the prospect of employing more than three reaction components to get derivatized Gewald products. Cyanoacetamides have been once used in the 3-component Gewald reaction as a potentially flexible component. Cyanoacetamides were utilized in the cases which were based on hydrazides and aromatic amides. 11 Actually, just only some references to cyanoacetamides generated from aliphatic amines have been found in the Gewald-3CR. 12 By including cyanoacetamides as generalpurpose components and therefore making the Gewald MCR efficient, a considerable expansion of the present Gewald-3CR is defined. We proposed to examine the Gewald-3CR of cyanoacetamides and share our findings here. We reacted cyanoacetamides (Scheme 1) with various aldehydes/ketones and S 8 in the existence of DMAP in methanol at 50 C for 45-50 min.
Gewald-3CR primary products also act as a forerunner for a range of additional molecules, including kinase inhibitor thienopyrimidines, 13 thienoquinazolines, 14 pyrimidines, 15 diazocompounds, 16 Schiff bases, 17 tetracyclic thienopyrimidinones, 18 and N-thieno-maleinicacid amides". 19 Following a study of the literature, it was revealed that synthesis has gotten a lot of attention due to its applications. 20 As a consequence, ACPHTC and its derivatives were synthesized, and the vibrational frequency and NMR data were compared to those derived from a theoretical study using computational methodologies. DFT calculations were used in this work as the computational technique. The DFT calculations 21 are beneficial for determining the link between the geometry and electronic properties of the compound and the results are consistent with experimental evidence. 22 In our previous articles, we have studied "AMPYRA, amine dimedone, phthalic anhydride, sulfanilic acid, and 2-amino-N-cyclopropyl-5-ethyl-thiophene-3-carboxamide-" 23a-d by utilizing DFT with optimized molecular shape, vibrational frequency, MEP, ELF, NLO properties, NBO, FMO, molecular docking and drug similarities in our current works. 23 This work produces an X-ray of ACPHTC and determines its crystal structure. The B3LYP/ 6-311þþG(d,p) basis set was used in this work for DFT computations. The vibrational wavenumbers (FT-infrared), 1 H and 13 C NMR, and UV-Vis spectra analysis observed and calculated results were reported. Using tabular and graphical representations, the energies of the FMO involving the HOMO and the LUMO were examined. The reactive regions in a compound and its entire reactivity were revealed using NLO, NBO, and NHO, as well as Molecular Electrostatic Potential (MEP). Hirshfeld's surface was used to find intermolecular interactions in the crystal structure of ACPHTC. Drug potentiality, effectiveness, and similarity were evaluated using the ADMET methodology and molecular docking simulations using various membrane proteins, lipase, and hydrolase target proteins (3EQM, 4KFP, 6ME6, 4JT8, 5D7Q, 5SVF, 3ICQ, 4Y2B,  4DBU, 4UC1).

Materials
Cyclopropanamine, methylbenzylamine, ethylcyanoacetate, and all aldehydes and ketones were purchased from TCI, India. S 8 was acquired from Rankem, India. Qualigens Fine Chemicals provided solvents such as methanol, hexane, and ethyl acetate, which were purified and dried using conventional procedures. 24 In a recent study, we provided spectral information. 25

Experimental section
In a reaction flask, "0.5 mmol of 2-cyano-N-cyclopropylacetamide, 0.5 mmol of nonylaldehyde, 0.5 mmol of S 8 , and 20mg of DMAP" were added to 5ml of MeOH. The reaction mixture was heat to 50 C with good stirring for 45-50 min. The combination of ethanol and water (2:1, 5 ml) was used to work up the product, and the solution was then filtered through a separating funnel. After that, the filtrate was concentrated on rotovap. The solid residue was then purified via silica gel column chromatography (solvent hexane: ethyl acetate 7:3) ( Figure SF1(A,C,E)). The procedure of Section 2.2.1 was followed employing "(0.5 mmol) of 2-cyano-N-cyclopropylacetamide, (0.5 mmol) of isovaleraldehyde, (0.5 mmol) of S 8 , and 20 mg of DMAP" in 5 ml of MeOH. The reaction mixture was allowed to heat to 50 C with good stirring for 45-50 min. The combination of ethanol and water (2:1, 5 ml) was used to work up the product, and the solution was then filtered through a separating funnel. After that, the filtrate was concentrated on the rotovap. The solid residue was then purified via silica gel column chromatography (solvent hexane: ethyl acetate 7:3) ( Figure SF2(A-C)). The same procedure was followed employing "(0.5 mmol) of 2-cyano-N-cyclopropylacetamide, (0.5 mmol) of cyclohexanone, (0.5 mmol) of S 8 , and 20 mg of DMAP in 5 ml of MeOH". The reaction mixture was allowed to heat to 50 C with good stirring for 45-50 min. The solid residue was then purified via silica gel column chromatography (solvent hexane: ethyl acetate 7:3) ( Figure  SF3(A-C) The same procedure was followed employing "(0.5 mmol) of 2-cyano-N-cyclopropylacetamide, (0.5 mmol) of 4-methylcyclohexanone, (0.5 mmol) of S 8 , and 20 mg of DMAP in 5 ml of MeOH". The reaction mixture was allowed to heat to 50 C with good stirring for 45-50 min. The solid residue was then purified via silica gel column chromatography (solvent hexane: ethyl acetate 7:3) ( Figure  SF4(A-C)). In a reaction flask "0.5 mmol of 2-cyano-N-(1-phenylethyl)acetamide, 0.5 mmol of butyraldehyde, 0.5 mmol of S 8 , and 20mg of DMAP were added to 5 ml of MeOH". The reaction mixture was allowed to heat to 50 C with good stirring for 45-50 min. The combination of ethanol and water (2:1, 5 ml) was used to work up the product, and the solution was then filtered through a separating funnel. After that, the filtrate was concentrated on the rotovap. The solid residue was then purified via silica gel column chromatography (solvent hexane: ethyl acetate 7:3) ( Figure  SF5(A-C)). Colorless cubes. Yield: 97%. M.P. 195-197 C. 1  In a reaction flask "0.5 mmol of 2-cyano-N-(1-phenylethyl)acetamide, 0.5 mmol of isovaleraldehyde, 0.5 mmol of S 8 , and 20 mg of DMAP were added to 5 ml of MeOH". The reaction mixture was allowed to heat to 50 C with good stirring for 45-50 min. The combination of ethanol and water (2:1, 5 ml) was used to work up the product, and the solution was then filtered through a separating funnel. After that, the filtrate was concentrated on the rotovap. The solid residue was then purified via silica gel column chromatography (solvent hexane: ethyl acetate 7:3) ( Figure  SF6(A-C)). Brown solid. Yield: 95%. M.P.180-183 C. 1  In a reaction flask "0.5 mmol of 2-cyano-N-(1-phenylethyl)acetamide, 0.5 mmol of nonylaldehyde, 0.5 mmol of S 8 , and 20mg of DMAP were added to 5 ml of MeOH". The reaction mixture was allowed to heat to 50 C with good stirring for 45-50 min. The combination of ethanol and water (2:1, 5 ml) was used to work up the product, and the solution was then filtered through a separating funnel. After that, the filtrate was concentrated on the rotovap. The solid residue was then purified via silica gel column chromatography (solvent hexane: ethyl acetate 7:3) ( Figure  SF7(A-C)). Dark brown solid. Yield: 79%. M.P. 178-180 C. 1

Computational details
The Gaussian 16 software package 26 was employed to accomplish all calculations. The Gauss view 6 molecular visualization programme 27 was used for post-processing. The geometry of the ACPHTC was optimized using two different approaches, including Hartree Fock (HF) and DFT using B3LYP 28a,b functionals with 6-31þþG(d,p) and 6-311þþG(d,p) basis sets, Whereas, the molecular geometry of ACPHTC derivatives were optimized using B3LYP functionals with 6-311þþG(d,p) basis sets. The parameter bond length and angle with molecular geometries were analyzed using a Gaussian output file as a source. PED values were obtained using VEDA version 4 software to co-relate all vibrational assignments with PED percentage. 29 The 1 H and 13 C NMR spectra data were analyzed using the Gage-invariant atomic orbital (GIAO) method. UV-Visible spectra were produced using the Time-Dependent DFT approach, which is a strong and effective computational tool for studying the ground and excited state features that have been employed by many researchers in recent years in their DFT investigations. 30 The nucleophilic and electrophilic areas of ACPHTC and its derivatives were determined by looking at the MEP, which summarizes the distribution of charge of the molecule. 31 MEP diagrams for the ACPHTC and its derivatives were constructed in optimal geometry using the Gauss View 6 program. Chemical potential, global hardness and softness, and electrophilicity 32,33 were also estimated. Crystal Explorer 4.1 34 was used to produce the Hirshfeld surfaces and their associated 2D plots, Hirshfeld analysis was carried out to examine the configurations of intra and intermolecular interactions in the crystal. Hirshfeld analysis is a helpful tool for understanding unit cell packing in crystals. The study is based on a 3D graph representation in the region of space where molecules interact with nearby molecules, and the 2D fingerprint plot highlights the type of contact between atoms.The mapping of normalized contact (d norm ), can be expressed by an equation as follows: r vdw e r i vdw and r e vdw represent the radii of atoms . The interactions in the compound crystal were examined in relation to how far away the nearest atom's internal d i and exterior nuclei were from the surface d e . . 34 The d i and d e in the 2D fingerprint plot tell about the type of intermolecular interactions within the molecules in the crystal. 34 The Autodock 4.2.6 software tool was used to perform molecular docking investigations. 35 After docking all the docked conformations were viewed using Discovery studio visualize for 2D bonding interactions.

Optimized molecular geometry
The basic goal of any computational approach is to acquire the compound's optimum shape. Tables  3 and 4 show the optimized bond length and angle for ACPHTC (1) derived using the B3LYP and HF methods with the 6-31þþG(d,p) and 6-311þþG(d,p) basis sets, respectively, whereas Figure 1(B) shows the optimized structure of ACPHTC (1) and its derivatives (Figures SF16-SF21). Tables  ST4-ST5 show the optimized bond length and bond angle for ACPHTC derivatives ( Figures  SF16-SF21) derived using the B3LYP methods with the 6-311þþG(d,p) basis set. ACPHTC and its derivatives possess a C1 point group. Geometry-optimized structure of ACPHTC is strikingly similar to the molecule's actual crystal structure. There is a considerable accord among the estimated and observed geometric parameters, even though the molecule geometry in the gas phase may change from that in the solid phase due to prolonged hydrogen bonding and stacking interactions. From theoretical values, we can see that most of the optimum bond lengths and bond angles are somewhat shorter and longer than experimental values because theoretical calculations are for an isolated molecule in the gaseous phase and actual data are for a molecule in the solid state. When we compare the bond angle and bond length of ACPHTC obtained using the two techniques, we see that the DFT theory produces geometrical parameters that are substantially closer to experimental values. The average bond distances of C-C and C-N calculated by the DFT method with B3LYP/6-311þþG (d,p) basis sets are 1.3918 Å and 1.364 Å, respectively. The average bond length of C-H was calculated at 1.0842 Å and the bond length of C-O was calculated at 1.2442 Å. The carbon-sulfur bond length shows a relatively high value (1.7726 Å) because of the repulsion between the lone pair of an electron on the sulfur atom and the electron on the carbon atom in the ring. In ACPHTC, the bond angle S1-C2-N4 ¼ 121.3 (exp. 121.7 ) is larger than the S1-C2-C5 ¼ 111.2 (exp. 111.9 ) calculated by "DFT/B3LYP with 6-311þþG(d, p)" basis set method. Between B3LYP and experimental, the bond length RMSD is 0.902, while the R2 value is 0.813. These low values imply that observed and calculated structures are identical. The bond lengths and angles (Tables ST4-ST5) of all derivatives (2)(3)(4)(5)(6)(7) show only a small deviation in their values.

Vibrational assignment
The vibrational spectrum of a molecule is regarded as a distinct physical feature that defines the molecule. ACPHTC consists of 43 atoms, which have 123 modes of vibrations. The normal modes are determined using a 3n-6 active number of observable atoms pattern that excludes the translational and rotational degrees of freedom. The density functional approach was used to record and theoretically match infrared and FT-Raman spectra using B3LYP/6-311þþG(d,p). Figure 2(A-B) depict calculated and observed FT-IR and Figure SF9 depicts theoretical FT-Raman spectra, whereas Table ST6 lists spectral assignments as well as PED contributions. The levels have been methodically equalized using a scale factor of 0.961.

N-H vibrations
The stretching vibrations of N-H occur in the range 3000-3500 cm À1 in all heterocyclic compounds. 36 Tsuboi 37 calculated the N-H stretching frequency in aniline to be 3481 cm À1 . The stretching vibrations of N-H for ACPHTC have been seen at 3523, 3486, and 3332 cm À1 with the medium broadband and 73%, 55%, and 50% of PED contribution. For FT-IR, the experimental peak was found at 3304 cm À1 .

C-H vibrations
Asymmetric aromatic C-H stretching vibrations are generally in the range of 3100-3000 cm À1 , whereas symmetric stretching vibrations are in the range of 2990-2900 cm À1 . 38 For ACPHTC, the C-H stretching frequencies range from 2876 to 3099 cm À1 . As disclosed through PED assignments, 21

C-C and N-C Vibrations
The stretching vibrations modes of C-C are predictable in the area of 1650-1200 cm À1 . 39 In this work, stretching vibrations of C-C were observed in the area of 1555-181 cm À1 . PED data reflect a mixture of the range because other groups like C-C in and out-of-plane bending vibration interact with these ranges with comparably lower values. The aliphatic amines frequently overlap in N-C vibrations and fall in a composite area of 1020-1220 cm À1 . The theoretical frequencies are observed at 1468, 1446, 1228, 1203, 1149, and 946 cm À1 . Due to additional minor vibrations, there is a mixed mode of PED assignments.

S-C vibrations
Because of polarization, the typical S-C stretching vibrations in the range 720-580 cm À1 are predicted to be weak in Infrared bands. 40 For the current work, the observed density functional technique shows the range of (S-C) stretching vibrations at 695 cm À1 with 31% PED.

Magnetic resonance spectroscopy
For the structural revelation of organic molecules, NMR is a qualitative instrument broadly utilized in the chemical, fertilizer, and pharmaceutical industries (drugs). Table ST7 shows the actual and calculated values for 13 C and 1 H NMR of ACPHTC. In CDCl 3 solvent, the experimental 13 C and 1 H NMR were recorded and displayed in Figure SF1(A-D). The GIAO technique 41 3 . This discloses that carbon having a greater chemical shift is deshielded; because of the existence of an electronegative atom.

Molecular electrostatic potential
MEP (molecular electrostatic potential) is a useful descriptor for describing nucleophilic and electrophilic reactive sites and hydrogen bonding interactions. 42 The regions of electrophile and nucleophile reactivity were predicted using MEP at the B3LYP/6-311þþG(d,p) using Gauss View 6 software. As seen in Figure 3 and Figures SF22-SF27, the diverse electrostatic potential values are shown by distinct colors. The different electrostatic potentials at the surfaces are distinguished by unique shades, with red indicating the most negatively charged regions, blue indicating the most positively charged regions, and green indicating regions with nearly zero potential. On the basis of color coding, the electrostatic potential is arranged in ascending order as red < orange < yellow < green < blue. 43 In ACPHTC, and in its derivatives, negative (red to yellow) zones are found on oxygen atoms, which are linked to the strongest repulsion (electrophilic reactivity), whereas positive (blue) regions are found on nitrogen and hydrogen atoms, which are connected with the strongest attraction (nucleophilic reactivity). These maps of ACPHTC have a color code that ranges from À5.682 a.u (red) to þ5.682 a.u (green) (deepest blue). ACPHTC and all of its derivatives may have biological functions as a result of this structure-activity link.

Non-linear optical (NLO) analysis
Non-Linear Optical is at the forefront of existing research, because of its relevance in optoelectronic and photonics devices technology and applications. DFT has been successfully used in the study of organic NLO materials. The NLO activity of ACPHTC was confirmed using the B3LYP/ 6-311þþG(d,p) basis set. Because of highly strong interactions among the molecules, the dipole moment (l) was determined to be quite high at 2.7849 D, as shown in Table ST8. In this work, ACPHTC has a hyperpolarizability of 239.567 Â 10 À31 e.s.u, whereas standard urea has a hyperpolarizability of 0.9279310 À30 e.s.u. 44,45 The nonlinear optical characteristic is confirmed by the fact that ACPHTC is higher than the typical urea value. Using the density functional approach, the computed polarizability (a 0 ) is À1.86510 Â 10 À23 e.s.u, which is higher than the standard value of urea 0.38312 Â 10 À23 e.s.u. The title drug ACPHTC has been confirmed as a possible candidate for the creation of optoelectronic materials based on its initial hyperpolarizability.

NBO analysis
The information provided by the natural bond orbital analysis on interactions in filled and virtual orbital spaces can assist researchers in the understanding of intramolecular and intermolecular interactions. In NBO analysis, interactions between donors and recipients are represented using the second-order Fock matrix theory. All potential interactions between full (donor) Lewis-type NBOs and empty (acceptor) non-Lewis NBOs are evaluated for their energy relevance using second-order perturbation theory.The stabilization energy E(2) associated with delocalization is computed for each donor NBO (i) and acceptor NBO (j). 46 where qi, is the ith donor orbital occupancy, ei, ej are diagonal elements (orbital energies), and Fij is the NBO matrix off-diagonal element. The donor-acceptor interactions with regard to perturbation energies for the targeted drug ACPHTC are given in Table ST9.  Table ST10 shows all NBO labels, as well as hA and hB natural atomic hybrids that make up the natural bond orbital, the hybridization % (s, p, and d characters), and the polarization coefficient of atomic hybrids (cA, cB). The r (S1-C2) bond is formed from a sp 4.61 hybrid of S1 carbon (combination of 17.73% of s, 81.68% of p, 0.03% of d orbitals) and an sp 2.89 hybrid of C2 (combination of 25.63% of s, 74.19% of p, 0.18% of d orbitals). The polarization coefficients cA (0.6877) and cB (0.7260) differ due to the electronegativity of the S1 and C2 atoms. The greater polarization value of nitrogen (0.7694), on the other hand, implies that nitrogen is more electronegative than carbon (0.6387). This may be stated as follows: The vector specifying a hybrid p-azimuthal component (A) and polar (h) angles are utilized to determine its orientation. The deviation angles of hybrid A and B orbitals describe the bending nature of the bonds. The bending nature and geometrical variations of NHO are shown in Table  ST11. The NHO of rS1-C2, rS1-C3, rC2-N4, rC2-C5, rC3-C6, and rN4-H8 are bent by (7.6, 3.3), (7.6, 2.1), (1.8, 2.2), (91.3, 90), (84.1, 83.6) and (89.3, 89.1), respectively.

UV-Vis studies and electronic properties
Experimental and theoretical calculations were used to explore the ultraviolet spectra of ACPHTC. TD-DFT 48 has recently emerged as a powerful method for examining the static and dynamic characteristics of molecules in their excited states, providing for the optimum balance of precision and computing cost. 49 The TD-DFT/B3LYP technique and the 6-311þþG(d,p) basis set were used to compute the absorption maximum (k max ) of the ACPHTC molecule. The experimental spectra have been observed in two different solvents (DMSO and MeOH).To compare the experimental data, a combination of the solvent model and the TD-DFT approach is necessary for the computation of the absorption spectra. In the last two decades, PCMs 50 have emerged as the most effective methods for treating bulk solvent effects in both the ground and excited states. Table 5 shows the predicted frontier orbital energies, oscillatory strengths (f), absorption wavelengths (k), and excitation energies (E) for the gas phase and the DMSO and MeOH solvents. The visual absorption maxima of ACPHTC correlate to the electron transition between frontier orbitals, such as translation from HOMO to LUMO, according to calculations of molecular orbital geometry. Figure 4 shows the ACPHTC actual and theoretical UV vibrationally resolved spectra. Experimentally determined maximum absorption values in DMSO and MeOH are 309 nm and 307 nm, and theoretically calculated values in DMSO have been found to be 34472.92, 34864.91, 38601.67 cm À1 (290.08, 286.82, 259.06 nm) and in MeOH34560.03, 34843.94, 38608.13 cm À1 (289.35, 287.00, 259.01 nm). According to estimated absorption spectra, the highest absorption wavelength in DMSO and MeOH solvents corresponds to the electronic transition from HOMO to LUMO with 96.7% and 95.1% contribution, respectively. This transition is projected to take place as p-p Ã . In quantum chemistry, the HOMO and the LUMO are significant factors. Since HOMO is thought to be the orbital with the most electrons, it frequently serves as an electron donor for these electrons. On the other hand, LUMO is the innermost orbital that has free spaces to take electrons. 51 In accordance with the molecular orbital theory, 52 a transition state, transition of p-p Ã type is seen due to the interaction between a structure HOMO and LUMO orbitals. It follows that the HOMO energy is proportional to its ionisation potential while the LUMO energy is related to its electron affinity. The energy gap between the HOMO and the LUMO has recently been employed to demonstrate intramolecular charge transfer (ICT) bioactivity. The energy gap of ACPHTC was estimated as 4.7963 eV ( Table 6). There are nodes in every HOMO and LUMO.
T Red colour represents the positive phase, whereas green colour indicates the negative phase. The positive phase is denoted by the colour red, whereas the negative phase is shown by the colour green. Electrons are largely delocalized on the thiophene and cyclopropyl rings in the HOMO-2, HOMO-1, and HOMO, as seen in Figure 5. When transitions of electrons occur, some electrons will enter the LUMO, LUMO þ 1, and LUMO þ 2, and the electrons will mostly be delocalized on NH 2 and the aliphatic chain in the LUMO, LUMO þ 1, and LUMO þ 2.

Hirshfeld analysis (HF)
In order to offer complementary information on the impact of short interatomic contacts on molecular packing, the Hirshfeld surfaces estimated for ACPHTC were done in accordance with recent findings. 53 HF analysis is analyzed in crystals only. In this study, the Hirshfeld surface analysis of ACPHTC was performed using the Crystal Explorer software. 34 The HF surfaces of ACPHTC, comprising "d norm , d e , d i , shape index, curvedness, and fragment patches", are shown in Figure 6(A-F). Table 7 lists all 3D surfaces with the minimum, maximum, and mean values for d norm , d i , d e , shape index, curvedness, and fragment patch. ACPHTC molecular resolution chemical standard Figure 6(A) depicts the Hirshfeld surface (d norm ). The d norm surface had a brick red circular zone in some places of the Hirshfeld surface, indicating tight contact with surrounding molecules; dark red dots on d norm suggested short intermolecular interactions, whereas light red dots on d norm showed weak interatomic connections. As illustrated in Figure 6(A), the ACPHTC d norm revealed several red spots caused by hydrogen bonds between oxygen and hydrogen. The spots on the HF surface 54 that enclose a molecule where the electron density contribution from the molecule in question matches that of all other molecules constitute the molecule HF surface. For every position on the isosurface, two distances are calculated: de and di (de is  the separation between the spot and the closest atomic nucleus outside the surface), and (di is the distance between the spot and the nucleus closest to the surface). The surface of the electron density that encloses molecular interactions is indicated by the shape index's contours. 55 Patches of varied colors on the shape index surface exhibit intermolecular complementarity zones, as seen in Figure 6(D). The red highlighted patches illustrate the concave portions of atoms in the pstacked molecule atop the molecule. The ring structure of the molecule inside the crystal surface is depicted by the convex region in blue. The values of the shape index vary from "À0.9968 to 0.9971 Å". Curvedness is a measurement of a molecule shape's surface area. 56,57 Figure 6(E) depicts the curvedness of the ACPHTC molecule. Curvedness shows a range from "À3.4855 to 0.1902 Å". A low curvedness value correlates to a flat disc-like region on the surface, whereas a high curvedness value correlates to a sharp edge-like curvature and tends to disperse the surface into patches, revealing the interaction between surrounding molecules. Flat regions are divided by a blue edge, which represents stacking interactions.  Figure 7 shows 2D FPs with a d norm view of the connections for the crystal structure ACPHTC. According to the analysis, the computed distances from the surface to the nearest nuclei within and outside the surface were 1.5213 and 1.5410 Å, respectively. The E enrichment ratio was discovered to support the clear image of the kind and contribution of bonds formed in the molecule. As shown in Table 8, H-H produced the bulk of the molecular surface, accounting for 71.9%, followed by S-H (6.0%), C-H (4.5%), H-C (4.1%) and O-H (3.4%).

Drug-likeness
The goal of drug-likeness was to achieve efficient and well-ordered outcomes in drug development and ligand structural characteristics. Lipinski's rule, Veber rule, MDDR-like rule, BBB rule, Ghose filter, CMC-50 rule, and QED 58 were used to determine drug resemblance. ACPHTC and its derivatives have biological qualities, so they were used to test the effectiveness of the drug-likeness criterion. The significant ADME variables of the common derivatives of compound        29, and ACPHTC and its derivatives have the same bioavailability score of 0.55. The above comparison demonstrates that ACPHTC possesses sufficient biological properties. Figure SF11, depicting the drug similarity behavior of ACPHTC was provided.

Molecular docking
Molecular docking studies help medicinal chemists identify novel drugs at a low cost and in a short amount of time. The docking approach was used to discover the optimal match of ligands and proteins with the least amount of energy. 60 Molecular docking was used to determine ideal bonded residues, hydrogen bonds, predicted inhibition constants, binding energy, and RMSD of therapeutic molecules and their protein targets, as well as how minute the molecule binds to a known 3D structure receptor. The Gaussian-derived optimal structure of ACPHTC (1) and its derivatives (2-7) were converted to PDB files and docked with the Auto dock-vina 61-63 program. The Swiss ADME prediction site predicted all of the selected proteins, and the database was obtained from the Protein Data Bank (RCSB PDB). The top pose of binding of the molecule in 2D and 3D is shown in Figures 8-10 and Figures SF11-SF16, with the protein having a binding energy of À9.4 kcal/mol. Table 9 shows the bound residues, hydrogen bond number, bond length, inhibition constant, binding energy, and reference RMSD.   well with 5SVF has the lowest binding energy is À6.8 kcal/mol, and the ACPTBC is bound with the 3ICQ whose binding energy is À6.5 kcal/mol. Whereas, 4U7H, 4UC1, 6O6V, and 4AQD exhibited very lowest binding energy of À5.9, À6.1, À6.0, and À5.8 kcal/mol that bound well with ligands ACMTBC, AEPTC, AIPTC, and AHPTC. Because these chemicals bind strongly to low-binding-energy proteins, they might be used as potential anticancer, antimalarial, and antiviral treatments. Antimicrobial, antimalarial, antiviral, and anticancer effects of thiophene derivatives were examined by Romagnole et al., 64 Said et al., 65 and Bozorov et al., 66 indicating that ACPHTC and its derivatives can also demonstrate these capabilities.

Conclusion
Various DFT techniques using the 6-311þþG(d,p) basis set were used to conduct a comprehensive vibrational study of ACPHTC. The molecular formula of the ACPHTC was C 15 H 24 N 2 OS by confirmed single crystal XRD. ACPHTC, crystallizes in the Tetragonal crystal system, with an I-4 space group with Z ¼ 16 in the unit cell. In this present study, versatile DFT calculations were performed for ACPHTC and its derivative. Theoretical calculations of the optimized parameters and comparisons with experimental data were performed. The title molecule FT-IR spectra have been observed, computed, and mentioned with PED values. The stability of the ACPHTC, which results from the hyperconjugative interaction and the charge delocalization, was understood via NBO analysis. Maximum UV-visible absorption has been noted at wavelengths of 301 nm in the gas phase, 290 nm in DMSO, and 289 nm in MeOH, respectively. Furthermore, the charge transfer hypothesis of molecule-to-molecule interaction is supported by the sizeable difference between the HOMO and LUMO energy gaps. The electron density transfer from the lone pair LP (1) of the nitrogen atom (N16) to the anti-bonding orbital p Ã (C10-O15) with high stabilization energy of 50.09 kcal/mol has resulted in the observation of strong interaction. The computed values of l, a, and b for the ACPHTC molecule are 2.7849 D, À1.86510 Â 10 À23 , and 239.567 Â 10 À31 , respectively, which are greater than those of urea. The calculated energy gap is E ¼ 4.805 eV which is lower than urea (DE ¼ 6.7063 eV). Intermolecular interactions were examined utilizing Hirshfeld surface analysis of ACPHTC, which includes d norm , d i , d e , shape index, and curvature, as well as 2D fingerprint diagrams. 2D plots show that 71.9% of H-H was created, with S-H coming in second at 6.0%, C-H in third at 4.5%, and H-C in fourth place at 4.1%. Last but not least, research using molecular docking shows that AEPTC and ACMTBC have powerful antibacterial, antimalarial, antiviral, and anticancer properties because of their low binding energies.