Photophysical, antioxidant, antibacterial and NBO, LOL, ELF analysis of alkyl groups substituted calix[4]resorcinarenes

doi:10.21203/rs.3.rs-2707368/v1

In our work to investigate the photophysical, antibacterial, theoretical and topological analysis of four C-alkyl calix[4]resorcinarenes (C4RAs). The solvatochromism and photophysical properties of C4RAs in different solvents were recorded in both UV-Visible and fluorescence spectral studies. The total antioxidant capacity and antibacterial activity of four C4RAs were evaluated by phosphomolybdate assay and kirby-bauer method. Theoretical parameters such as HOMO, LUMO, energy gap and Mulliken atomic charges and NBO were optimized by DFT B3LYP 6-311G method. From the results of HOMO and LUMO energies were used to determine the theoretical parameters of four C4RAs. The nucleophilic and electrophilic substitution reactivity of four C4RAs were analyzed by molecular electrostatic potential map analysis. Natural bonding orbital analysis was used to determine the intramolecular charge transfer within the energy difference between acceptor and donor orbitals. The non-covalent interactions of four C4RAs were characterized by LOL and ELF topological analysis.

C-alkyl calix[4]resorcinarene

antioxidant capacity

antibacterial

DFT

NBO

LOL

ELF

Recent years, many researchers were focused on the calix[4]resorcinarenes supramolecular compound due to interesting properties and applications in the medicine, biology and ecology [1–7]. The position and intensity of absorption and emission bands on the different solvents were explained by the term solvatochromism [8]. These photophysical properties of supramolecules were governed by the intermolecular interaction between the solute with solvent [9]. The study of photophysical properties of calix[4]resorcinarenes in the presence of different solvents helps to scrutinize the effect of solvatochromism. The photophysical properties of various solvatochromic molecules were biologically active have attractive attention from scientific community. The solvatochromism was exists as the various organic molecules such as coumarin, chalcones, phatholocyanin and curcumin [10–14]. Besides photophysical investigations of fullerenes with calix[4]resorcinarenes and anthracene ended calix[4]resorcinarene reported from the previous literature [15, 16].

Antioxidants are the chemical substances can be block the harmful action of free radicals by scavenging the free radicals and detoxify the organism. Although the calix[4]resorcinarene derivatives have a electron donating hydroxyl groups that they are act as the potential antioxidant activity. The calix[4]resorcinarene compounds which can exhibit antimicrobial, anticoronovirus, anticonvulsant, antidepressant, anti-inflammatory, analgesic, antimalarial, antitumor, antifungal and antiviral activities [17]. Several bacterial stains causing infectious disease which seemed to be control are once again causing death every year due to the absence of suitable antibiotic drug. Remarkably the development of new antibiotics has failed to keep pace with the development of drug-resistance over past few decades. In particular attention has focused on the bacterial stain Staphylococcus aureus because the resistant against clinically used antibiotics like methicillin and vancomycin [18]. The fact that the compounds of resorcinol derivatives give the advantages to work as a perfect antioxidant properties and relatively low toxicity due to the high molecular weight (above 400 g/mol) of calix[4]resorcinarene derivatives.

In recent days, computational chemistry was used as accepted partner in experimental chemistry. A series of theoretical calculations have been intensively carried out few simple calixarene type molecules [19]. Density functional theory (DFT) has been received considerable attention owing to its implications in appraising a wide variety of chemical substances. “Ab initio” calculations of the electronic structure of atoms, molecules, crystals, surfaces of the molecules and their interactions were measured by using Density Functional Theory (DFT) method. The quantum mechanical approach of DFT calculations were used to understand the quantitative properties in different supramolecular system. Density Functional Theory calculations (DFT) was used to calculate and find out the conformational arrangement, total energy and stability of the calix[4]resorcinarene system [20].

Theoretical calculations using molecular mechanics, semi-empirical to density functional theory are employed to understand structural and spectral features of calix[n]arene (CX[n]) derivatives. Bernardino and Cabral predicted structure and energy rank order in calix[4]arene and thiacalix[4]arene conformers from the Hartree-Fock and density functional theory incorporating a variety of basis sets [21, 22]. Thus, partial cone or 1,2 and 1,3 alternate structures close-lying to the cone (lowest energy) conformer in thiacalix[4]arene (S-CX[4]) have been derived. The equilibrium structure and vibrational frequencies of p-tert-butyl-thiacalix[4]arene obtained by the gradient correlated density functional calculations incorporating Perdew-Burke-Ernzerhof (PBE) exchange-correlation [23]. Energies and cooperative hydrogen bonding in para-substituted calix[n]arenes and thiacalix[n]arenes studied to employing quantum chemical and density functional calculations [24].

A various number of quantum chemistry program suits available for the analysis of electronic structure and electron densities of molecules were analyzed by natural bonding analysis program [25]. The popular alternative graphical mapping analysis techniques were included as mulliken atomic charge analysis, electrostatic potential map (ESP), localized orbital locator (LOL) and electron localization function (ELF) analysis [26–28].

In our research work deals with the photophysical, biological, theoretical and topological analysis of four C4RAs (C4RA - compound 3a, CMC4RA - compound 3b, CEC4RA - compound 3c and CPrC4RA - compound 3d) supramolecules. The structural and spectral properties of four C4RAs were analyzed using FT-IR, ¹H-NMR, ¹³C-NMR, ESI-mass, UV-Visible and elemental (CHNS/O) analysis. The effect of solvent and their photophysical behavior of four C4RAs were determined by both UV-Visible and fluorescence spectral studies. Total antioxidant capacity of four C4RAs was evaluated by phosphomolybdate antioxidant assay. Kirby-Bauer susceptibility method was find out the antibacterial activity of four C4RAs against Gram positive and Gram negative bacterial stains used for bacterial infectious disease. Furthermore the structure and theoretical parameters of four C4RAs was optimized by DFT B3LYP 6-311G computational method. The various structural parameters such as energy, HOMO, LUMO energy structure, mulliken atomic charges, ESP, NBO, LOL and ELF were predicted for these compounds in the gaseous phase.

Solvent studies

The UV-Visible and fluorescence spectrum of compounds 3a-3d (C4RAs) were studied using different solvents and were shown in Figures 1 and 2. In their absorption spectral studies of compound 3a was revealed that the absorption bands at 285.5 nm for water, 283.5 nm for methanol, 283.0 nm for ethanol, 287.0 nm for dimethyl sulphoxide (DMSO) and 287.0 nm for dimethyl formamide. From the UV-Visible spectrum of compound 3a was recorded in methanol and ethanol as the solvents, the spectral bands blue shifted in the wavelength at 283.5 nm (shift = -2 nm) and 283.0 nm (shift = -2.5 nm) compared with the compound 3a in water as the solvent respectively. But in the case of compound 3a in the presence of dipolar solvents the spectral bands were red shifted for DMSO (+1.5 nm) and DMF (+1.5 nm) respectively. The emission spectrum was recorded in the different polar and dipolar solvents such as water, methanol, ethanol, DMSO and DMF. The compound 3a was shown the emission band at 320 nm in water, 317 & 427 nm in methanol, 319 nm in ethanol, 318 nm in DMSO and 321 & 430 nm in DMF respectively. In the case of methanol and dimethyl formamide (DMF), two emission bands observed in the region at 322 nm and 409 – 430 nm was due to the intermolecular interaction between the solvent and the cavity of compound 3a, 3b, 3c and 3d. The one major band around 317 nm to 326 nm was due to neutral hydroxyl group moiety of C4RAs macrocyclic ring system. The similar type of spectral shift of compound 3b, 3c and 3c in methanol, DMSO and DMF were followed this above manner. But in the case of compound 3b, 3c and 3d in the presence of ethanol as the solvent the observed UV-Visible spectral bands were red shifted in lower to higher wavelength. However, the results of UV-Visible and fluorescence spectrum of four C4RAs were displayed as the macrocyclic ring system undergoes n-π* transition [29].

The photophysical properties of four C4RAs were analyzed in different polar and dipolar solvents. Thus, the solvent and dielectric constant were the major factor to choose the solvents in photophysical properties. The irregular shifts of four C-alkyl were noticed (Figure 3 & Table 1) that the decreased the solvent polarity from water to dimethyl formamide (DMF). A linear plot of stoke’s shift values versus normalized Reichardt polarity scale (E_T^N) deals with solute and solvent interactions between the four C4RAs and solvents [30,31]. The solvatochromic behavior which caused by encapsulation of solvent molecule in the cavity of C4RAs involves through inter and intramolecular hydrogen bonding respectively.

Total antioxidant capacity by phosphomolybdate assay

This type of assay is based on the reduction of phosphomolybdate (VI) ion in the presence of an antioxidant, resulting to the formation of green Mo(V) phosphate complex measured spectrophotometrically [32].The antioxidant capacity of standard ascorbic acid (Figure 4) was resultant to the 75.25 μg/mL TAC, 97.96% of TAC and 9.36 μg/mL of IC₅₀ value respectively [33].The percentage of antioxidant capacity of four C4RAs was exhibited as the range at 89.72 – 93.65 %. From the results, compound 3d was shown as minimum percentage of antioxidant capacity compared to the compound 3a, 3b and 3c. IC₅₀ values of four C4RAs were calculated from the plot of % TAC vs concentration in the range of 9.42 - 58.99 μg/mL. The IC₅₀ values of the 3a, 3b and 3c exhibit as very strong antioxidants and the compound 3d only behaves as the strong antioxidant nature. The calculated total antioxidant activity of four C4RAs was found to be 97.93 – 106.21 μg/mL.

The quantitative phosphomolybdate antioxidant assay could be determining IC₅₀ value calculated from linear regression graphical representation method. The IC₅₀ was utilized to determine the antioxidant activity of four C4RAs. IC₅₀ value is defined as the concentration of antioxidant that inhibits the 50% of activity. The results total antioxidant capacity of four C4RAs was presented in Table 2. According to the level of the antioxidant capacity classified into four parts, which are very strong (IC₅₀ value is <50 μg/mL), strong antioxidants (IC₅₀ value is 51-100 μg/mL), moderate antioxidant (IC₅₀ value is 101-150 μg/mL) and weak antioxidant (IC₅₀ value is 151-200 μg/mL).

The mechanistic action of phosphomolybdate reagent (phosphomolybdenic acid) with the C4RAs was shown in Figure 5. In this mechanism, phosphomolybdenic acid contains the twelve Mo(VI) ion involves the abstraction of four electrons from the hydroxyl groups to reduced as four Mo⁵⁺ ion. The four electrons will be transfer to phosphomolybdenic acid to green coloured phosphomolybdenic reagent. The four electrons were transferred from the C4RAs one of the resorcinol ring oxidized and the Mo(VI) ion are reduced as four Mo(V) ions respectively [33,34].

From the results, the total antioxidant capacity by phosphomolybdate assay, the percentage of total antioxidant capacity was shown as maximum for compound 3a. By increasing the number of alkyl chains from compound 3a to 3d, when the % of TAC was decreases due to that the electron releasing substituents (+I effect) present in the methine bridges.

Antibacterial study

Many of the synthetic C4RAs were classified as medicinal and antibacterial activity [35].The Muller Hinton Agar media (Hi media) was used for the antibacterial studies of four C4RAs tested against five bacteria such as escherchia coli, klebsiella pneumoniaei, streptococus pneumoniae, staphylococcus aureus and pseudomonas aeruginose. Four C4RAs were tested for their in vitro antibacterial activities against Gram positive bacteria - Staphylococcus aureus, Streptococus pneumoniae and Gram-negative bacteria - Escherchia coli, Klebsiella pneumoniaei, Pseudomonas aeruginose by Kirby-Bauer method using amikacin as the control drug for antibacterial activities, respectively. Paper disc method was used for carrying out bacterial activity. The results of antibacterial studies were presented in Figure 6 and Table 3. The antibacterial effect of four C4RAs was compared with standard antibiotic drug amikacin. From the results of antibacterial activity the compound 3a was shown as the moderate activity against the escherchia coli (5/17) bacterial stain and the same compound exists as sensitive against the Streptococus pneumonia (10/15), Staphylococcus aureus (14/19) and Pseudomonas aeruginose (12/15) bacterial stains. Compound 3b was exhibited the moderate resistant against the gram negative bacteria such as Klebsiella pneumoniaei (4/15) and gram positive bacterial stains such as Staphylococcus aureus (8/15) & Streptococus pneumonia (8/19). The gram negative bacterial stain escherchia coli (10/17) and moderate resistant with the gram negative bacterial stains streptococus pneumonia sensitive against the compound 3c and 3d. The gram positive bacterial stain Staphylococcus aureus was shown as moderate activity against 3c (7/15). The selective antibacterial activities of four C4RAs were suggested that the find applications in variety of different environments where selective to fighting against some selective gram positive and gram negative bacterial stains [36]. In their results of antibacterial studies, broad inhibition zones of four C4RAs were shown as potential antibacterial activity.

Theoretical Studies

DFT – B3LYP 6-311G method was used to calculate the theoretical parameters of four C4RAs supramolecular ring system. The calculated parameters were presented in Table 4 & Figure 7-8.

From the Table 4 the calculated HOMO and LUMO energy values were observed at the ranging from -5.24 to -5.20 eV and -1.15 to -1.08 eV. The energy values of four C4RAs the calculated energy gap values of compound 3a as -4.08 eV, compound 3b as -4.12 eV, compound 3c as -4.06 and compound 3d as -4.07 eV respectively. The compound 3b was shown as the minimum energy values and the compound 3c have maximum energy gap values. The energy gap between the HOMO and LUMO was very important to determine the reactivity order due to the electron mobility. From this result, smaller energy values were indicates that the compounds act as the more reactive nature. According to the energy gap values, the reactivity of the compounds should be followed as 3b > 3a > 3d > 3c [37].

The mathematical equation [2]-[16] was used to calculate the values of theoretical parameters. From the results of electronic ionization potential and the electron affinity of four C4RAs were observed at 5.20 - 5.24 eV and 1.08 - 1.15 eV respectively. However, the highest electronegativity (3.20 eV) and lowest chemical potential (-3.20 eV) values were appeared as the compound 3a. The freedom of electrons which can be determined by the electronegativity values of the compounds. Chemical reactivity increases with increasing the values of electronegativity. Based on the chemical potential index values were decreased with increasing the chemical reactivity of the compound [37]. From the Table 4, chemical hardness and chemical softness values were ranging from 2.03 – 2.04 eV and 0.484 – 0.492 eV. Electrophilicity index values of four C4RAs were observed at the 2.39 to 2.49 eV. The electron accepting and electron donating capability values minimum for compound 3b and the maximum values for compound 3a respectively. The net electrophilic and global softness values were calculated from 9.88 – 10.20 eV and 0.242 to 0.246 eV. Thus, the minor variations in the values of four C4RAs were appeared in the values of ΔE_{back donation}, nucleophilicity index, ∆N_max and optical softness values. The calculated dipole moment of C4RAs were appeared as 10.13 debye units for compound 3a, 10.09 debye units for compound 3b, 10.25 debye units for compound 3c and 10.39 debye units for compound 3d. The energy values of four C4RAs were obtained values ranging from by DFT B3LYP 6-311G program the values -1.05 x 10⁶ to -1.35 x 10⁶ kcal mol^-1. From the results of energy values the order of stability follows compound 3d > 3c > 3b > 3a due to the increasing the alkyl groups present in the methine bridges [38].

Mulliken atomic charge analysis

Mulliken atomic charge analysis of four C4RAs were calculated from the DFT B3LYP 6-311G program method given in the Table S1-S4 and the generated plot of mulliken atomic charges were presented in Figure 9. It was clear that the eight oxygen atoms in the four C4RAs shown as the 34O, 36O, 39O, 41O, 44O, 46O, 49O, 51O for compound 3a, 34O, 36O, 39O, 41O, 44O, 46O, 49O, 51O for compound 3b, 37O, 39O, 42O, 44O, 47O, 49O, 52O, 54O for compound 3c and 37O, 39O, 42O, 44O, 47O, 49O, 52O, 54O for compound 3d respectively. This oxygen atoms was exist as the negative mulliken atomic charge values ranging from the -0.6962 to -0.6164 atomic units respectively. But their hydrogen atoms in the hydroxyl groups were shown as the positive charges on the mulliken atomic charges in the atoms like 35H, 37H, 40H, 42H, 45H, 47H, 50H, 52H for compound 3a, 35H, 37H, 40H, 42H, 45H, 47H, 50H, 52H for compound 3b, 38H, 40H, 43H, 45H, 48H, 50H, 53H, 55H for compound 3c and 38H, 40H, 43H, 45H, 48H, 50H, 53H, 55H for compound 3d. Since the positive atomic mulliken charges were ranging from 0.3651 to 0.4020 atomic units respectively. Thus the remaining carbon and hydrogen atoms of four C4RAs were possessed the positive and negative values of mulliken charges respectively. However the results, the negative peak values present in the oxygen and carbon atoms of four C4RAs were reacted with electrophilic compounds.

Natural bonding orbital (NBO) analysis

The delocalization of orbitals scheme were obtained from the second order perturbation bonding-antibonding (donor-acceptor) NBO analysis. In this type of analysis to gives information about the stabilized molecular interactions from the change in electron density on the (π*) antibonding orbitals and E⁽²⁾ energies were calculated from DFT method [39]. Natural bonding orbital analysis was used as the efficient method for studied intra and intermolecular hydrogen bonding, intramolecular charge transfer (ICT) interaction and delocalization of π electrons present in the C4RAs ring systems [40].

Table S5 was presented second order perturbation analysis of donor-acceptor interactions and their stabilization energies of four C4RAs. From their NBO analysis results larger E⁽²⁾ values were indicates that the more strong interactions between the electron donors to electron acceptors. It was confirm that the more electron donating tendency for donors to electron acceptors and greater extent of conjucation occurs in the aromatic system of C4RAs [41].The stabilization of donor-acceptor interactions were occurred delocalization of electron density between the occupied bond or lone pair (Lewis type) NBO orbitals and formally unoccupied antibond (non-lewis type or Rydgberg) NBO orbitals. The NBO analysis of titled compounds was performed at the B3LYP/6-311G level in order to elucidate the delocalization of electron density in the molecules.

The interactions between the bonding π orbitals to the antibonding π* orbitals were shown as the π(C-C)-π*(C-C) interactions were obtained the stabilization energy values ranging from 15.80 to 27.54 kcal/mol. From the results of NBO analysis, the interactions between the LP(O)-π*(C-C) orbitals were observed stabilization energy values of four C4RAs ranging from 23.54 – 25.90 kcal/mol for compound 3a, 23.32 – 25.17 kcal/mol for compound 3b, 22.92 – 24.71 kcal/mol for compound 3c and 22.91 – 22.49 kcal/mol for compound 3d respectively. NBO analysis were revealed that the π*(C-C)-π*(C-C) interactions were gives the strong stabilization energy values 118.73 to 288.83 kcal/mol respectively. The above results the π-π*and LP(O)-π*(C-C) interactions were observed at the same stabilization energy values from the NBO analysis results. But the type of interaction such as π*(C-C)-π*(C-C) was observed the greater the value stabilization energy value leads to the strong donor-acceptor interactions. However, the excited state electron donor and electron acceptor sites present in the C4RAs were occurred most possible interactions such as intramolecular charge transfer interactions and delocalization of π-electrons [42,43].

Molecular electrostatic potential map (MESP) analysis

The molecular electrostatic potential (MESP) at a point in the space around C4RAs were investigated by the formation of net electrostatic effect produced the point through total charge distribution in the molecule. Additionally, surface mapping of MESP was helps to understanding the reactivity of many chemical systems in both electrophillic and nucleophilic reactions studied biological strategies and hydrogen bonding interactions [44].The most important property of MESP mapping was used to investigate the density of electron distribution over the molecule through molecular electrostatic potential calculations.

The electrophilic and nucleophilic attack reactivity of the C4RAs were investigated by molecular electrostatic potential map analysis. In the case of an electrophilic attack in the molecule, it was preferred go to the most negative portion (Red color) of the molecule due the site with the most dominant electron effect. On the other hand, in the case of a nucleophilic attack, it will go to the most positive portion (blue color) of the molecule. The MESP for the target molecule created on the isodensity is investigated and shown in Figure 10. The region with red color is the representation of the negative charge with higher electron density while the portion in blue color is electropositive with lower electron density. Figure 10 was clearly evident to that the maximum electron density was located near the oxygen atoms of the hydroxyl groups were suitable site for electrophilic attack. The positive electrostatic potential was concerted to near the hydrogen atom of -OH group act as the better site for the nucleophilic attack. The intermediate colour of red and blue colour regions included as green and yellow colors act as the neutral portions. The red colored oxygen atoms (red region) in the four C4RAs were attracted with blue colored region of hydrogen atoms in the hydroxyl groups involved through the intramolecular hydrogen bonding interactions [45,46].

Topological Analysis

The topological analysis of localized orbital locator (LOL) and electron localized function (ELF) with relief map projection were performed for the covalent and non-covalent interactions of investigated compounds. The covalent bonded regions for the organic compounds with electron rich functional groups reveal that the molecular space at which probability to finding out high electron pair density [47].Figure 11 was shown the molecular structure, color shaded maps (LOL and ELF with relief map), contour map of LOL for the compound 3a, 3b and 3c respectively. The higher end is represented by red colour in between brown and yellow to green for middle and the representation of lower end by blue colour in the pictures. From the figure, the approximate values were optimized in the range between 0.64 to 0.80 for LOL and 0.8 to 1.0 for ELF in four C4RAs. It can be seen that the covalent regions have high LOL and ELF (red regions) values, the electron depletion regions between the valence shell and inner shell are shown by blue circles around nuclei. From the results of colour filled ELF map, the red coloured regions of resorcinarenes hydroxyl hydrogen atoms of 3a contains H35, H37, H40, H42, H45, H47, H50 and H52, 3b have H35, H37, H40, H42, H45, H47, H50 and H52, 3c contains H38, H40, H43, H45, H48, H50, H53 and 3d have H18, H20, H33, H35, H43, H45, H48, H50 respectively. The lowest LOL and ELF values of aromatic carbon atoms and oxygen atoms present in hydroxyl groups were shown as C2, C3, C11, C13, C17, C18, C26, C28, O34, O36, O39, O41, O44, O46, O49, O51 for 3a, C2, C3, C11, C13, C17, C18, C26, C28, O34, O36, O39, O41, O44, O46, O49, O51 for compound 3b, C2, C3, C12, C16, C18, C19, C28, C30, O37, O39, O42, O44, O47, O49, O52, O54 for compound 3c, C2, C3, C12, C14, C18, C19, C38, C28, , O17, O19, O32, O34, O42, O44, O47, O49 for compound 3d. The disynaptic nature of the non-bonding lone pair electrons on oxygen atoms in the C4RAs which was found at blue colour regions in the ELF and LOL map [48,49]. This disynaptic nature of oxygen atoms from the eight hydroxyl groups attract with the neighbouring hydroxyl group hydrogen atoms in another ring of the compound resulting to form four intramolecular hydrogen bonds [50].In these molecules, there was eight hydroxyl groups in four resorcinarene rings involved in the intramolecular hydrogen bond between the oxygen and hydrogen atoms. The strong intramolecular hydrogen bonding in these compounds was clearly shown in this figure through indication of colour. From the 2D plot of the LOL and ELF maps which they exhibit that the intramolecular hydrogen bonding interactions between the lone pair of electrons in the oxygen and hydrogen atoms labeled as O51….H35, O39….H37, O44….H42, O46….H50 for compound 3a, O51….H35, O39….H37, O44….H42, O46….H50 for compound 3b, O54….H38, O42….H4, O47….H45, O49….H53 for compound 3c and O42….H40, O45….H47, O49….H53, O54….H38 for compound 3d respectively.

Materials

The starting materials such as resorcinol, acetaldehyde, propionaldehyde, butyraldehyde, dimethyl sulphoxide (DMSO), ethanol, methanol, and hydrochloric acid were purchased from Sigma-Aldrich and HiMedia chemical company. In the experimental section analytical grade (AR) reagents and solvents can be used without further purification. All the solvents and double distilled water used throughout the experimental work.

Instruments

FTIR spectrum was recorded at resolution on a Jasco FT-IR spectrometer model FT/IR – 4700 at room temperature. Measurements of FTIR wavenumber ranging from 4000 – 400 cm^-1 were carried out using KBr pellet method. Nuclear magnetic resonance (¹H-NMR and ¹³C-NMR) were recorded on a BrukerAvance III HD Nanobay 400 mHz FT-NMR SPECTROMETER recorded in deuterated dimethyl sulphoxide (DMSO) using tetramethylsilane (TMS) as the reference, the chemical shifts are given in δ units (ppm). Absorption spectral measurements were carried out with Perkin Elmer instrument Lambda 25 UV-Visible spectrometer. Fluorescence spectrum was carried out using Jasco Fluorescence Spectrophotometer model FB - 8300. ESI mass spectra were taken on XEVO G2-XS QTOF instrument. The elemental analysis for Carbon, hydrogen and oxygen was carried out using CHNS Elemental Analyzer – Perkin Elemer – 2400 CHNS/O Series. SYSTRONICS visible spectrophotometer model 166 used to determine optical density values in antioxidant studies.

Synthesis of calix[4]resorcinarenes (C4RAs) from resorcinol and aliphatic aldehydes

A modified synthesis of compound 3a, 3b, 3c and 3d were synthesized via cyclocondensation reaction between 5.50 g resorcinol (50 mmol) mixed with 50 mmol solution of aliphatic aldehydes (such as 1.50 mL formaldehyde, 2.80 mL acetaldehyde, 3.65 g propionaldehyde and 3.60 g of butyraldehyde) dissolved in 50 mL 1:1 ethanol-water as the solvent. Then the mixture was added 5 mL of concentrated hydrochloric acid stirred 90⁰C for 1-6 hour. Subsequently the reaction mixture and formed product was cooled in an ice bath and followed by filtration. The yellow colour solid precipitate of compound 3a, 3b and 3c was separated, washed with the mixture of ethanol-water and allowed to dry.

Compound 3a : Colour: orange; Yield: 4.62 g; % yield: 71.82 %; Melting point: >300 ⁰C (decompose). FTIR (KBr): 3271 cm^-1 (stretching OH); 2952 cm^-1 (stretching CH); 1612 and 1512 cm^-1 (stretching Ar-C=C), 1450 cm^-1 (bending CH); 1388 cm^-1 (bending OH), 1296, 1219, 1157 and 1041 cm^-1 (stretching C-OH). ¹H-NMR (DMSO-d₆): Crown (C_4v) – 3.428 ppm (methine bridge, m); 6.538 ppm (aromatic proton, n); 6.652 ppm (aromatic proton, o); 9.029 ppm (hydroxyl proton, p). Chair (C_2h) – 3.428 ppm (methine bridge, m); 6.252 and 6.291 ppm (aromatic proton, n); 6.035 and 6.056 ppm (aromatic proton, o); 8.803 and 8.844 ppm (hydroxyl proton, p). ¹³C-NMR (DMSO-d₆): 29.04 ppm (methine bridge, m); 123.56 ppm (aromatic carbon, n); 152.35 ppm (aromatic carbon, n); 102.57 ppm (aromatic carbon, p); 125.77 ppm (aromatic carbon, q); 22.09 ppm (methyl carbon, a). UV-Visible (Ethanol/water mixture): 220.0 and 281.0 nm. Fluorescence (Ethanol/water mixture): 317.0 and 461.0 nm. ESI-mass (DMSO): [M+1]⁺- 489.17 m/z; Molecular Mass: 388.17 g/mol (calculated); 488.49 g/mol (found). Elemental (CHNS/O) analysis: C – 68.61 %: H – 4.93 % and O – 26.46 %: Molecular formula: C₂₈H₂₄ O₈.

Compound 3b: Colour: yellow; Yield: 5.26 g; % yield: 77.35 %; Melting point: >300 ⁰C (decompose). FTIR (KBr): 3363 cm^-1 (stretching OH); 2970 cm^-1 (stretching CH); 1612 and 1512 cm^-1 (stretching Ar-C=C), 1427 cm^-1 (bending CH); 1381 cm^-1 (bending OH), 1203, 1111 and 1041 cm^-1 (stretching C-OH). ¹H-NMR (DMSO-d₆): Crown (C_4v) – 4.449 ppm (methine bridge, m); 6.150 ppm (aromatic proton, n); 6.760 ppm (aromatic proton, o); 8.540 ppm (hydroxyl proton, p); 1.284 ppm (methyl proton, a). ¹³C-NMR (DMSO-d₆):29.04 ppm (methine bridge, m); 123.56 ppm (aromatic carbon, n); 152.35 ppm (aromatic carbon, n); 102.57 ppm (aromatic carbon, p); 125.77 ppm (aromatic carbon, q); 22.09 ppm (methyl carbon, a). UV-Visible (Ethanol/water mixture): 207.0 and 280.0 nm. Fluorescence (Ethanol/water mixture): 320, 359 and 465 nm. ESI-mass (DMSO): [M+1]⁺-545.24 m/z; Molecular Mass: 544.59 g/mol (calculated); 544.24 g/mol (found). Elemental (CHNS/O) analysis: C – 70.49 %: H – 5.98 % and O – 23.53 %: Molecular formula: C₃₂H₃₂ O₈.

Compound 3c: Colour: yellow; Yield: 6.95 g; % yield: 92.67 %; Melting point: >300 ⁰C (decompose).FTIR (KBr):3348 cm^-1 (stretching OH); 2959-2871 cm^-1 (stretching CH); 1614 and 1506 cm^-1 (stretching Ar-C=C), 1434 cm^-1 (bending CH); 1377 cm^-1 (bending OH), 1203, 1149 and 1057 cm^-1 (stretching C-OH). ¹H-NMR (DMSO-d₆): Crown (C_4v) – 4.096 ppm (methine bridge, m); 6.154 ppm (aromatic proton, n); 7.219 ppm (aromatic proton, o); 8.962 ppm (hydroxyl proton, p); 0.793 ppm (methyl proton, a); 2.095 (methylene proton, b). ¹³C-NMR (DMSO-d₆): 35.62 ppm (methine bridge, m); 123.52 ppm (aromatic carbon, n); 152.03 ppm (aromatic carbon, n); 102.72 ppm (aromatic carbon, p); 125.49 ppm (aromatic carbon, q); 13.09 ppm (methyl carbon, a); 27.21 ppm (methylene carbon, b). UV-Visible (Ethanol/water mixture): 203.0 and 280.5 nm. Fluorescence (Ethanol/water mixture): 324, 359 and 461 nm. ESI-mass (DMSO): [M+1]⁺- 601.28 m/z; Molecular Mass: 600.70 g/mol (calculated); 600.28 g/mol (found). Elemental (CHNS/O) analysis: C – 71.17 %: H – 6.61 % and O – 22.22 %: Molecular formula: C₃₆H₄₀ O₈.

Compound 3d: Colour: Orange: Yield: 7.45 g; % yield: 90.85 %; Melting point: >300 ⁰C (decompose). FTIR (KBr): 3301 cm^-1 (stretching OH); 2952 and 2865cm^-1 (stretching CH); 1613 and 1507 cm^-1 (stretching Ar-C=C), 1435 cm^-1 (bending CH); 1376 cm^-1 (bending OH), 1156, 1199 and 1078 cm^-1 (stretching C-OH).¹H-NMR (DMSO-d₆): Crown (C_4v) – 4.223 ppm (methine bridge, m); 6.142 ppm (aromatic proton, n); 7.235 ppm (aromatic proton, o); 8.936 ppm (hydroxyl proton, p); 0.902 ppm (methyl proton, a); 1.195 (methylene proton, b), 2.080 ppm (methylene proton, c). ¹³C-NMR (DMSO-d₆):36.18 ppm (methine bridge, m); 123.66 ppm (aromatic carbon, n); 152.05 ppm (aromatic carbon, n); 102.80 ppm (aromatic carbon, p); 125.50 ppm (aromatic carbon, q); 14.38 ppm (methyl carbon, a); 21.15 ppm (methylene carbon, b); 33.03 ppm (methylene carbon, c). UV-Visible (Ethanol/water mixture): 205.0 and 281.5 nm. Fluorescence (Ethanol/water mixture): 324 and 463 nm. ESI-mass (DMSO): [M+1]⁺- 657.34 m/z; Molecular Mass: 656.80 g/mol (calculated); 656.34 g/mol (found). Elemental (CHNS/O) analysis: C – 73.15 %: H – 7.23 % and O – 19.74 %: Molecular formula: C₄₀H₄₈ O₈.

UV-Visible and fluorescence spectral analysis

A stock solution of four C4RAs was prepared different solvents (water, methanol, ethanol, DMSO, DMF) in 10 mL SMF. The final concentration of solution in all flasks was 1 x 10^-4M and the solutions are allowed to stand for 1 hr. After 1 hr, UV-Visible and fluorescence spectrum of the solutions was recorded at the range of 200 to 510 nm.

Total antioxidant capacity (TAC) by phosphomolybdate method

The total antioxidant capacity of four C4RAs were analyzed by the following method described [51]. A stock solutions (1000 μg/mL) of four C4RAs were prepared, 50 mg of the compound dissolved in minimum amount of dimethyl sulphoxide (DMSO) and the solution was made upon 25 mL SMF using methanol as the solvent. The various concentrations (ranging from 10-200 μg/mL) of four C4RAs were prepared in methanol solution. A volume of 1 mL different concentrations (μg/mL) was added to the 10 mL phosphomolybdate reagent solution (4mM ammonium molybdate, 28mM sodium phosphate, 0.6 M sulphuric acid) in 25 mL SMF. A mixed solution was heated at water bath set at 95 ⁰C for 90 minutes. Then after 90 minutes the mixture was allowed to cool off to room temperature and then the mixture was analyzed in spectrophotometer at 695 nm. Ascorbic acid was used as the standard and the high percentage of total antioxidant capacity inhibition indicates high antioxidant capacity vice verse. The percentage of inhibition was calculated by using the formula [1].

Where, A(sample) is the sample with sample and reagent solution

A(control) is the sample with methanol and reagent solution

Linear regression y = mx + c made concentration as x-axis and % inhibition as ordinate y-axis. The 50% concentration (IC₅₀) of total antioxidant activity was calculated as the concentrations of sample that inhibited 50% of antioxidant activity under these conditions.

Antibacterial studies

The antibacterial studies of four C4RAs carried out prepare plates of Hinton Agar (M173) for use in the Kirby-Bauer susceptibility test described in most lab manual and use an American Type Culture collection strain of Escherichia coli, Klebsiella pneumoniaei, Streptococcus pneumonia, Staphylococcus aureus and Pseudomonous aeruginose [52]. The plates were prepared from the components (such as beef extract, agar, starch, casein hydroxylate, distlled water) poured and dried on a petridish. The organism was streaked on the medium and test compound (1gm in DMSO) was placed on medium. Then the plates were incubated at 37 ⁰C for one over night. The observed susceptibility was shown the clearance around the compound placed in the petridish. A drug (Amikacin) was used as the standard drug for the comparison.

Theoretical studies

The theoretical calculations were executed with Gaussian 09W software package [53]. In this computational software, the initial geometry of four C4RAs were constructed with the help of Spartan 08 and then optimized by DFT B3LYP 6-311G method. Energy, HOMO energy, LUMO energy and HOMO-LUMO energy gap, Mulliken atomic charges, electrostatic potential map and other theoretical parameters of the systems using the following expressions [2-16] respectively [54,55].

$$\text{I}\text{o}\text{n}\text{i}\text{s}\text{a}\text{t}\text{i}\text{o}\text{n} \text{p}\text{o}\text{t}\text{e}\text{n}\text{t}\text{i}\text{a}\text{l} \left(\text{I}\right)=-{\text{E}}_{\text{H}\text{O}\text{M}\text{O} } \left[2\right]$$

$$\text{E}\text{l}\text{e}\text{c}\text{t}\text{r}\text{o}\text{n} \text{a}\text{f}\text{f}\text{i}\text{n}\text{i}\text{t}\text{y} \left(\text{A}\right)=-{\text{E}}_{\text{L}\text{U}\text{M}\text{O}} \left[3\right]$$

$$\text{E}\text{l}\text{e}\text{c}\text{t}\text{r}\text{o}\text{n}\text{e}\text{g}\text{a}\text{t}\text{i}\text{v}\text{i}\text{t}\text{y} \left({\chi }\right)=\frac{\text{I}+\text{A}}{2} \left[4\right]$$

$$\text{C}\text{h}\text{e}\text{m}\text{i}\text{c}\text{a}\text{l} \text{p}\text{o}\text{t}\text{e}\text{n}\text{t}\text{i}\text{a}\text{l} \left({\mu }\right)=-\left({\chi }\right) \left[5\right]$$

$$\text{C}\text{h}\text{e}\text{m}\text{i}\text{c}\text{a}\text{l} \text{h}\text{a}\text{r}\text{d}\text{n}\text{e}\text{s}\text{s} \left({\eta }\right)=\frac{\text{I}-\text{A}}{2} \left[6\right]$$

$$\text{C}\text{h}\text{e}\text{m}\text{i}\text{c}\text{a}\text{l} \text{s}\text{o}\text{f}\text{t}\text{n}\text{e}\text{s}\text{s} \left(\text{S}\right)=\frac{1}{{\eta }} \left[7\right]$$

$$\text{E}\text{l}\text{e}\text{c}\text{t}\text{r}\text{o}\text{p}\text{h}\text{i}\text{l}\text{i}\text{c}\text{i}\text{t}\text{y} \text{i}\text{n}\text{d}\text{e}\text{x} \left({\omega }\right)=\frac{{{\mu }}^{2}}{2{\eta }} \left[8\right]$$

$$\text{E}\text{l}\text{e}\text{c}\text{t}\text{r}\text{o}\text{n} \text{a}\text{c}\text{c}\text{e}\text{p}\text{t}\text{i}\text{n}\text{g} \text{c}\text{a}\text{p}\text{a}\text{b}\text{i}\text{l}\text{i}\text{t}\text{y} \left({{\omega }}^{+}\right)=\frac{{\left(\text{I}+3\text{A}\right)}^{2}}{16\left(\text{I}-\text{A}\right)} \left[9\right]$$

$$\text{E}\text{l}\text{e}\text{c}\text{t}\text{r}\text{o}\text{n} \text{d}\text{o}\text{n}\text{a}\text{t}\text{i}\text{n}\text{g} \text{c}\text{a}\text{p}\text{a}\text{b}\text{i}\text{l}\text{i}\text{t}\text{y} \left({{\omega }}^{-}\right)=\frac{{\left(3\text{I}+\text{A}\right)}^{2}}{16\left(\text{I}-\text{A}\right)} \left[10\right]$$

$$\text{N}\text{e}\text{t} \text{e}\text{l}\text{e}\text{c}\text{t}\text{r}\text{o}\text{p}\text{h}\text{i}\text{l}\text{i}\text{c}\text{i}\text{t}\text{y} \left({\varDelta {\omega }}^{2}\right)=\left({{\omega }}^{+}-{{\omega }}^{-}\right) \left[11\right]$$

$$\text{G}\text{l}\text{o}\text{b}\text{a}\text{l} \text{s}\text{o}\text{f}\text{t}\text{n}\text{e}\text{s}\text{s} \left(\text{s}\right)=\frac{1}{2{\eta }} \left[12\right]$$

$${ \varDelta \text{E}}_{\text{B}\text{a}\text{c}\text{k} \text{d}\text{o}\text{n}\text{a}\text{t}\text{i}\text{o}\text{n}}=\frac{-{\eta }}{4} \left[13\right]$$

$$\text{N}\text{u}\text{c}\text{l}\text{e}\text{o}\text{p}\text{h}\text{i}\text{l}\text{i}\text{c}\text{i}\text{t}\text{y} \text{i}\text{n}\text{d}\text{e}\text{x} \left(\text{N}\right)=\frac{1}{{\omega }} \left[14\right]$$

$$\text{A}\text{d}\text{d}\text{i}\text{t}\text{i}\text{o}\text{n}\text{a}\text{l} \text{e}\text{l}\text{e}\text{c}\text{t}\text{r}\text{o}\text{n}\text{i}\text{c} \text{c}\text{h}\text{a}\text{r}\text{g}\text{e} \left({\varDelta \text{N}}_{\text{m}\text{a}\text{x}}\right)=\frac{-{\mu }}{{\eta }} \left[15\right]$$

$$\text{O}\text{p}\text{t}\text{i}\text{c}\text{a}\text{l} \text{s}\text{o}\text{f}\text{t}\text{n}\text{e}\text{s}\text{s} \left({{\sigma }}_{0}\right)=\frac{1}{\varDelta \text{E}} \left[16\right]$$

Natural bonding orbital (NBO) analysis

DFT B3LYP 6-311G was used to study the second order perturbation energy (E⁽²⁾) and the donor-acceptor interactions [56].The obtained stabilization energy was carried out in NBO 6.0 software [57].

Topology analysis

The topology (ELF, LOL and ELF with projection map) was important tool for performing covalent bonding analysis, as they reveal regions of molecular space where the probability of finding an electron pair is high [58,59].

The conclusion of our work, four C4RAs were investigated that the photophysical, antioxidant, antibacterial, theoretical, Mulliken atomic charge analysis, NBO analysis and topological analysis. UV-Visible and fluorescence spectral studies were used to determine the solvatochromism and photophysical characterization in different solvents. The results of phosphomolybdate antioxidant assay of four C4RAs were behaves as the strong antioxidants from the values of % TAC and IC₅₀. The presence of electron releasing substituents on the methine bridges to enhanced the highest value of % TAC of compound 3a. Four C4RAs behaves the potential antibacterial activity against some selective gram positive and gram negative bacterial stains. Reactivity of four C4RAs was investigated by theoretical parameters, mulliken atomic charge analysis, NBO analysis and ESP analysis. The non-covalent interactions of four C4RAs were analyzed by LOL and ELF topological analysis.

Ethical Approval

This work is not relevant to analysis for both human and/or animal studies with our prepared samples.

Competing interests

Authors declare that there are no conflicts of interest.

Authors' contributions

Sathiyaseelan Kasi: Preparation of samples, Writing - original draft. Antony Muthu Prabhu Albert: Conceptualization, Methodology, Theoretical Software, Supervision

Funding

No specific funding was received for this Research work.

Availability of data and materials

All data generated or analyzed during this study are included in supplementary information file.

CD Gutsche, In Calixarenes Revisited. Monographs in Supramolecular Chemistry. Stoddart, J. F., Ed.; RSC: London, (1998)
Gutsche CD, Calixarenes An introduction. RSC, Cambridge, UK, (2008)
Mandolini L, Ungaro R, Calixarenes in Action. Imperial College, London, (2000)
Asfari Z, Bohmer V, Harrowfield J, Vicens J, Calixarenes. Kluver Academic, Netherlands, (2001)
Calixarenes, Beyond, Neri P, Sessler JL, Wang MX (Eds.), Springer, Netherlands (2016) 1062
Vicens J, Harrofield J, Calixarenes in nanoworld, Springer, Netherlands (2007) 396
Perret F, Coleman AW (2011) Biochemistry of anionic calix[n]arenes. Chem Commun 47: 7303-7319
Marini A, Munoz-Losa A, Biancaradi A, Mennucci B (2010) What is Solvatochromism?. J Phys Chem B 114: 17128-17135
de Rezende LCD, Vaidergorn MM, Moraes JCB, da Silva Emery F (2014) Synthesis, photophysical properties and solvatochromism of meso-substituted tetramethyl BODIPY dyes. J Fluoresc 24: 257-266
Sharma M, Pal U, Kumari M, Bagchi D, Rani S, Mukherjee D, Bera A, Pal SK, Dasgupta TS, Mozumdar S (2021) Effect of solvent on the photophysical properties of isoxazole derivative of curcumin: A combined spectroscopic and theoretical study. J Photochem Photobiol A: Chem 40: 1-13
Kumari R, Varghese A, George L, Sudhakar YN (2017) Effect of solvent polarity on the photophysical properties of chalcone derivatives. RSC Adv 7: 24204-24314
Beeby A, Parker AW, Simpson MS, Phillips D (1992) Photochemistry of bis(2,2′-bipyridyl)(methylene-linked diamine)ruthenium(II) complexes, [Ru(bipy)₂(L)]²⁺ (L = H₂N-(CH₂)_n-NH₂; n = 2 and 3). J Photochem Photobiol B Biol 69: 73-81
Pramod AG, Renuka CG, Nadaf YF (2019) Electronic structure, optical properties and quantum chemical investigation on synthesized coumarin derivative in liquid mediafor optoelectronic devices. J Fluoresc 29: 953–968
Budziak I, Karcz D, Makowski M, Rachwal K, Starzak K, Matwijczuk A, Mysilwa-Kurdziel B, Oniszczuk A, Combrzynski M, Podlesna A (2019) Non-typical fluorescence effects and biological activity in selected 1,3,4-thiadiazole derivatives: spectroscopic and theoretical studies on substituent, molecular aggregation, and ph effects. Int J Mol Sci 20: 1-28
Mukherjee S, Bauri AK, Bhattacharya S (2013) Photophysical investigations on determination of molecular structure and binding strength of supramolecular complexation between fulleropyrrolidine and a designed bisporphyrin in solution. Spechim Acta A Mol Biomol Spectrosc 109: 32-36
Knyazeva IR, Gerasimova TP, Kolesnikov IE, Syakaev VV, Katsyuba SA, Burilov AR (2020) Photophysical properties of new anthracene-ended calix[4]resorcinols. Mendeleev Commun 30: 650-653
Muneer S, Memon S, Pahnwar QK, Bhatti AA, Khokhar TS (2017) Synthesis and investigation of antimicrobial properties of pyrrolidine appended calix [4] arene. J Anal Sci Technol 8: 1-6
Grundmann H, Aires-de-Sosusa M, Boyee J, Tiemersma E (2006) Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat. Lancet 368: 847-885
Mohammed-Ziegler I, Billies F (2007) Optical spectroscopy and theoretical studies in calixarene chemistry. J Incl Phenom Macrocycl Chem 58: 19–42
Grimme S, Antony J, Schwabe T, Muck-Lichtenfeld C (2007) Density functional theory with dispersion corrections for supramolecular structures, aggregates, and complexes of (bio)organic molecules. Org Biomol Chem 5: 741-758
Bernardino RJ, Cabral BJC (1999) Structure, conformational equilibrium, and proton affinity of calix[4]arene by density functional theory. J Phys Chem A 103: 9080-9085
Bernardino RJ, Cabral BJC (2001) Structure and conformational equilibrium of thiacalix[4]arene by density functional theory. J Mol Struct Theochem 549: 253-260
Furer VL, Borisoglebskaya EI, Zverev V, Kovalenko VI (2007) DFT and IR spectroscopic analysis of p-tert-butylthiacalix[4]arene. Spectrochim Acta A Mol Biomol Spectrosc 63: 207-212
Novikov AN, Shapiro YE (2013) Energy and geometry of cooperative hydrogen bonds in p-substituted calix[n]- and thiacalix[n]arenes: a quantum-chemical approach. J Phys Chem A. 116: 546−559
Glendening ED, Landis CR, Weinhold F (2013) NBO 6.0: Natural bond orbital analysis program. J Comput Chem 34: 1429
Singh UC, Kollman PA (1984) An approach to computing electrostatic charges for molecules. J Comp Chem 5: 129
Weinhold F, Landis CR, Glendening ED (2016) What is NBO analysis and how is it useful?. Int rev Phy Chem 35: 399-340
Rajalakshmi K, Vetrivel M (2020) NBO and topology (MESP, ELF, LOL) analysis of 2-hydroxypropanamide. Int J Adv Sci Res Eng Trend 5: 50-58
Shalini N, SarahR (2001) Principles and applications of solvatochromism. Appl Spectrosc. 55: 362A-370A
Evale BG, Hanagodimath SM, Ahmed I, Kulkarni MV (2009) Estimation of dipole moments of some biologically active coumarins by solvatochromic shift method based on solvent polarity parameter, E(T)(N). Spectrochim Acta A Mol Biomol Spectrosc 73 (2009) 694-700
Kumari R, Varghese A, George L, Sudhakar YN (2017) Effect of solvent polarity on the photophysical properties of chalcone derivatives. RSC Adv 7: 24204-24214
Prieto P, Pineda M, Aguilar M (1999) Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. Anal Biochem 269: 337-341
Trang DHT, Son HL, Trung PV (2018) Investigation on the in vitroantioxidant capacity of methanol extract, fractions and flavones from Oroxylumindicum Linn bark. Braz J Pharm Sci 54: 1-7
Sadeer NB, Montesano D, Albrizio S, Zengin G, Mahomoodally MF (2020) The versatility of antioxidant assays in food science and safety—chemistry, applications, strengths, and limitations. Antioxidants 9: 1-39
Makwana BA, Bhatt K, Vyas D, Gupte HS, Jain V (2014) Synthesis, characterisation, binding behaviour and antimicrobial activity of azocalix[4]resorcine dye derived from 8-aminoquinoline. Sch Acad J Pharm 3: 463-470
Greenwood D, Finch R, Davey P, Wilcox M, Antibacterial chemotherapy, Oxford University press, Oxford, (2007)
Abdou A, Omran OA, Nafady A, Antipin IS (2022) Structural, spectroscopic, FMOs, and non-linear optical properties exploration of three thiacaix(4) arenes derivatives. Arab J Chem 15: 1-11
Shebitha AM, Sreejith SS, Sherly Mole PB, Nithiya Mohan, Avudaiappan G, Hiba K, Priya KS, Sreekumar K (2020) Facile synthesis, X-ray diffraction studies, photophysical properties and DFT-D based conformational analysis of octa and dodecacyanomethoxycalix[4]resorcinarenes. J Mol Struct 1214: 1-27
Thomson HW, Torkington P (1945) The vibrational spectra of esters and ketones. J Chem Soc 171: 640-645
Gassoumi B, Ghalla H, Chaabane RB (2019) DFT and TD-DFT investigation of calix[4]arene interactions with TFSI ion. Heliyon 5: 1-7
Szafran M, Komasa A, Adamska EB (2007) Spectroscopic (FT-IR, FT-Raman, NMR) investigation on 2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]ethyl(2S)-2-amino-3-methylbutanoate by density functional theory. J Mol Struct Theochem 827: 101-107
Sajana D, Erdogduc Y, Reshmyb R, Derelid Ö, Kurien Thomasb K, Hubert Joee I (2011) DFT-based molecular modeling, NBO analysis and vibrational spectroscopic study of 3-(bromoacetyl)coumarin. Spectrochim Acta A Mol Biomol Spectrosc 82: 118-125
Suresh S, Gunasekaren S, Srinivasan S (2014) Spectroscopic (FT-IR, FT-Raman, NMR and UV–Visible) and quantum chemical studies of molecular geometry, Frontier molecular orbital, NLO, NBO and thermodynamic properties of salicylic acid. Spectrochim Acta A Mol Biomol Spectrosc 132: 130-141
Sjoberg P, Politzer P (1990) Use of the electrostatic potential at the molecular surface to interpret and predict nucleophilic processes. J Phys Chem 94: 3959-3961
Sebastian S, Sylvestre S, Jayabharathi J, Ayyapan S, Amalanathan M, Oudayakumar K, Herman IA (2015), Study on conformational stability, molecular structure, vibrational spectra, NBO, TD-DFT, HOMO and LUMO analysis of 3,5-dinitrosalicylic acid by DFT techniques. Spectrochim Acta A Mol Biomol Spectrosc 136: 1107–1118
Samsonowicz M (2014) Molecular structure of phenyl- and phenoxyacetic acids – spectroscopic and theoretical study. Spectrochim Acta A Mol Biomol Spectrosc 118: 1086–1097
Jacobsen H (2009) Localized-orbital locator (LOL) profiles of transition-metal hydride and dihydrogen complexes. Can J Chem 87: 695-973
Michalski M, Gordon AJ, Berski S (2019) Topological analysis of the electron localisation function (ELF) applied to the electronic structure of oxaziridine: the nature of N-O bond. Struct Chem 30: 2181-2189
Fathima Rizwana B, Muthu S, Christian Prasana J, Christina Susan Abraham Raja M (2018) Spectroscopic (FT-IR, FT-Raman) investigation, topology (ESP, ELF, LOL) analyses, charge transfer excitation and molecular docking (dengue, HCV) studies on ribavirin. Chem. Data Collect. 17-18: 236-250
Abraham CS, Muthu S, Prasana JG, Fathima Rizwana B, Armakovic S, Armakovic SJ (2018) Vibrational and electronic absorption spectroscopic profiling, natural hybrid orbital, charge transfer, electron localization function and molecular docking analysis on 3-amino-3-(2-nitrophenyl) propionic acid. J Mol Struct 1171: 733-746
Jimoh MO, Afolayan AJ, Lewu FB (2019) Antioxidant and phytochemical activities of Amaranthus caudatus L. harvested from different soils at various growth stages. Sci Rep 9: 1-14
Neeraja Rani G, Budumuru R, Rao Bandaru N (2017) Antimicrobial activity of honey with special reference to methicillin resistant Staphylococcus aureus (MRSA) and methicillin sensitive Staphylococcus aureus (MSSA). J Clin Diagnostic Res 11: 5-8
Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman AR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J and Fox DJ, Gaussian, Inc., Wallingford CT (2013)
Surendra Babu N, Jayaprakash D (2015) Global and reactivity descriptors studies of cyanuric acid tautomers in different solvents by using of density functional theory (DFT). Int J Sci Res 4: 615-620
EL Ouafy H, Aamor M, Oubenali M, Mbarki M, EL Haimouti A, EL Ouafy T (2002) Molecular Structure, electrostatic potential and HOMO, LUMO studies of 4-aminoaniline, 4-nitroaniline and 4-isopropylaniline by DFT. Sci Tech Asia 27: 9-19
Chung LW, Sameera WMC, Ramozzi R, Page AJ, Hatanaka M, Petrova GP, Morokuma K (2015) The ONIOM method and its applications. Chem Rev 115: 5678–5796
Glendening ED, Landis CR, Weinhold F (2013) NBO 6.0: Natural bond orbital analysis program. J Comp Chem 34: 1429-1437
Silvi B, Savin A (1994) Classification of chemical bonds based on topological analysis of electron localization functions. Nature 371: 683–686
Jacobsen H (2009) Localized-orbital locator (LOL) profiles of transition-metal hydride and dihydrogen complexes. Can J Chem 87: 695–973

Table 1. UV –Visible and fluorescence spectrum of four C4RAs in different solvents (Concentration – 1 x 10^-4 M ).

Compound	Solvent	UV-Visible		Fluorescence	υ_a (cm^-1)	υ_f (cm^-1)	Stokes shift (cm^-1)	E_T^N
Compound	Solvent	λ_max	logε	λ_em	υ_a (cm^-1)	υ_f (cm^-1)	Stokes shift (cm^-1)	E_T^N
3a	Water	285.5	2.5682	320.0	35026	31250	3776	1.00
	Methanol	283.5	3.6394	317.0 427.0	35273	31546 23419	3727 11854	0.76
	Ethanol	283.0	4.0240	319.0	35336	31347	3397	0.65
	DMSO	287.0	3.9881	318.0	34843	31446	3697	0.44
	DMF	287.0	3.9969	321.0 430.0	34843	31152 23256	3691 11587	0.40
3b	Water	280.5	2.96	319.0	35650	31348	4302	1.00
	Methanol	261.5	4.2898	322.0 427.0	38240	31056 23419	7184 14821	0.76
	Ethanol	282.5	3.8382	324.0	35398	30864	4979	0.65
	DMSO	287.0	3.9148	322.0	34843	31055	3788	0.44
	DMF	285.5	3.8627	322.0 409.0	35026	31056 24450	4150 10756	0.40
3c	Water	281.5	2.4624	320.0	35524	31250	4274	1.00
	Methanol	261.0	4.2842	323.0 427.0	38314	30960 23419	7354 14895	0.76
	Ethanol	284.0	3.8363	325.0	35211	30769	4442	0.65
	DMSO	287.0	3.7259	323.0	34843	30960	3883	0.44
	DMF	286.0	4.0174	324.0 409.0	34965	30864 24450	4101 10515	0.40
3d	Water	277.5	2.1139	321.0	36036	31152	4884	1.00
	Methanol	261.0	4.2926	324.0 427.0	38314	30864 23419	7450 14895	0.76
	Ethanol	284.0	3.7966	325.0	35211	30769	4442	0.65
	DMSO	287.0	3.3444	325.0	34843	30769	4074	0.44
	DMF	285.5	3.5478	326.0 409.0	33840	31056 24450	2784 9390	0.40

Table 2. Total antioxidant capacity (TAC) data for four C4RAs.

Parameters	Standard	3a	3b	3c	3d
IC₅₀(μg/mL)	9.36	9.42	39.56	13.14	58.99
% TAC	97.76	93.65	92.06	91.67	89.72
TAC (μg/mL)	75.25	97.93	99.56	106.21	105.57

IC₅₀ value is >50 μg/mL (very strong), 51-100 μg/mL (Strong), 101-150 μg/mL (Moderate), 151-200 μg/mL (Weak)

Table 3. The antibacterial activity (zone of inhibition in mm) of four C4RAs

Bacterial Stains	A*	3a	3b	3c	3d
Escherchia coli	17	5	n/a	10	10
Klebsiella pneumoniaei	15	n/a	4	n/a	n/a
Streptococus pneumoniae	15	10	8	5	5
Staphylococcus aureus	19	14	8	7	n/a
Pseudomonas aeruginose	15	12	n/a	n/a	n/a

Inhibition zone: n/a – Resistant: 1-8 mm – Moderate resistant; above 9 mm – Sensitive

Table 4. DFT B3LYP 6-311G method data’s for four C4RAs.

Parameters	3a	3b	3c	3d
E_HOMO(eV)	-5.24	-5.20	-5.21	-5.20
E_LUMO(eV)	-1.15	-1.08	-1.15	-1.13
E_HOMO- E_LUMO (eV)	-4.08	-4.12	-4.06	-4.07
I (eV)	5.24	5.20	5.21	5.20
A (eV)	1.15	1.08	1.15	1.13
χ (eV)	3.20	3.14	3.18	3.17
μ (eV)	-3.20	-3.14	-3.18	-3.17
η (eV)	2.04	2.06	2.03	2.04
S (eV)	0.489	0.484	0.492	0.491
ω (eV)	2.49	2.39	2.48	2.48
ω⁺ (eV)	1.15	1.08	1.15	1.14
ω^-(eV)	4.35	4.22	4.33	4.31
∆ω^±(eV)	10.20	9.88	10.11	10.07
s (eV)	0.244	0.242	0.246	0.245
ΔE_{back donation}	-0.51	-0.52	-0.50	-0.50
N	0.40	0.42	0.40	0.40
∆N_max	1.56	1.52	1.56	1.55
σ₀	-1.96	-1.94	-1.96	-1.96
μ (Debye)	10.13	10.09	10.25	10.39
E (kcal. mol^-1)	-1.06 x 10⁶	-1.15 x 10⁶	-1.25 x 10⁶	-1.35 x 10⁶

I – Ionisation potential; A – Electron affinity; χ – Electronegativity; μ – Chemical potential; η – Chemical hardness; S – Chemical softness; ω – Electrophilicity index; ω⁺ - Electron accepting capability; ω^- - Electron donating capability; ∆ω^± - Net electrophilicity; s - Global softness; N – Nucleophilicity index and σ₀ – Optical softness.

No competing interests reported.

Supplementaryinformation.docx

Photophysical, antioxidant, antibacterial and NBO, LOL, ELF analysis of alkyl groups substituted calix[4]resorcinarenes

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Results And Discussions

Experimental Section

Conclusion

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1