8-Aminoquinoline-Based Promising Zn Complexes with Dicyanamide and Tricyanomethane Anions: Supramolecular R₄⁴(8)/R₂²(16) Synthons, DFT Rationalization, and Biological Insights

Abstract

Considering the new crystal engineering integrity utilizing the DFT and the issues surrounding antimicrobial resistance in complexes, there is a pressing need to tackle antifungal photodynamic therapy about global health challenges. Within the sphere of this study, we meticulously introduce the synthesis, characterization, and single-crystal structure of two 8-aminoquinoline-based Zn complexes [Zn{(8-AMQ) (X)}₂], X = dca (1) and TCM (2). The X-ray study reveals that the complexes crystallize in the monoclinic and triclinic space groups P2₁/c and P-1. The crystal packing in both complexes feature N–H···N hydrogen bonds as well as weak C–H···N interactions. The Hirshfeld surface provides quantitative insight into various supramolecular interactions, including π···π stacking, at large Cg···Cg distances. FMO supports the complexes' conductive behavior, excellent stability, and reactivity parameters. DOS investigation suggests good conductivity and reactivity properties. NBO analyzed that 2 exhibits a greater reactive and high potential charge transfer mechanism. The QTAIM/NCI-RDG plot ensured N···Zn/H···N interactions and explored new supramolecular R₄⁴ (8)/R₂²(16) crystal engineering synthons. The Trypan blue exclusion method was used to evaluate cytotoxicity against the DLA cell line, demonstrating 1's effectiveness against the cell, the lowest % of cell death, and a promising anticancer agent. The Zn complex antifungal photodynamic therapy finding showed significant activity against C. albicans.

Introduction

N-rich 8-aminoquinoline (8-AMQ) and its metal complexes have recently gained attention for their medicinal antiprotozoal properties¹ and diverse boundless applications in coordination chemistry.² Thus, exploring the flexibility of 8-AMQ organic ligand (L^ORG) in biological and supramolecular chemistry is limitless.^1,2 The 8-AMQ-uracil metal complexes have shown promising biological properties (anticancer and antimalarial activity, superoxide scavenging, and antimicrobial activities),^1,3 offering hope for new potential applications. 8-AMQ possesses a significant chelating planar arrangement and showcases exceptional properties, making it a fascinating attraction in supramolecular chemistry.^2,4 The ligand NH₂ functional group’s ability to bind with Mⁿ⁺ (metal) ions and form H-bonding and its potential for impressive engagement in π–π stacking interactions with aromatic C₆H₆ moiety and regulate interlocking network interpenetration (Scheme S1).^2,4 Interpreting the ″supramolecular″ term is strongly linked to manipulating self-assemblies via interactions between M (metal) and L^ORG and various intermolecular forces.⁵ The crucial factors for controlling self-assembly under crystal engineering include the M-center, used co-ions (X) nature (X = dca/TCM), L^ORG steric and conformational properties, and the reaction medium.^2,6 Generally, supramolecular networks in polymers can be developed by utilizing CB (coordination bonds), H-bonds, and aromatic π–π stacking interactions.² Recently, synthetic chemists have been using dicyanamide (dca) and tricyanomethane (TCM) coligands to broaden the scope of supramolecular chemistry and crystal engineering in their synthesized metal complexes.⁷ Notably, the exploration of [C(CN)₃]⁻ and [N(CN)₂]⁻ as ligands in coordination chemistry started just three decades ago.⁸ These ions are utilized as building blocks due to their versatile binding propensity with Mⁿ⁺ ions (Scheme S2–S3), which enhance the flexibility of creating discrete molecules or polymeric networks.⁷ Scientist Madelung published the first report on DCA involving coordination compounds. In 1922, Kern discovered its ability to coordinate with 3d transition Mⁿ⁺ ions, which Kohler et al. further investigated in the 1960s and 1980s.⁸ Therefore, extensive research has been conducted using transition metal based on DCA/TCM anions (Scheme S1).⁷ This research has examined novel crystal structures and their properties concerning supramolecular chemistry and new bonding concepts (Spodium/σ/π-hole).⁹ Therefore, extensive studies on d¹⁰ metal complexes provide a solid foundation for further research.¹⁰ Again, Zn metal is well-known in biology, and some of its complexes can mimic the active sites of zinc metalloenzymes.¹¹ The d¹⁰ electronic configuration of Zn(II) allows for different coordination geometries in its complexes.^12,7d These are all intriguing sights for synthetic chemists pursuing Zn(II) metal ion research. Furthermore, FMO/ESP/NBO/QTAIM/NCI-RDG/ELF-LOL studies are gaining popularity and becoming common in exploring the unique properties of synthesized complexes.^13,14 This trend is not temporary but is rising.¹⁵ Meanwhile, cancer research and antifungal photodynamic therapy (APDT) have gained popularity among new-generation scientists. Extensive research has already focused on nonplatinum-based metal-chemotherapeutic drugs for treating a more comprehensive range of cancers with reduced toxicity.¹⁶ DLA cells play a crucial role in this research. Various Zn complexes have been tested for their cytotoxicity against DLA cells.¹⁶ Further, antimicrobial resistance research is a significant global health concern. C. albicans is a common cause of invasive fungal infections. APDT is an alternative treatment that can eliminate microorganisms.¹⁷

Considering the precedence significance of the 8-AMQ ligand and its complexes, we synthesize, and X-ray characterize two Zn complexes. DFT study investigates the Zn complex’s reactivity and supramolecular and hydrogen bonding (N···H/H···N) perspectives. The QTAIM/NCI-RDG explores supramolecular R₄⁴ (8)/R₂²(16) synthons under crystal engineering. The cytotoxicity of the complex and its antifungal photodynamic therapy were analyzed in detail.

Experimental Section

Materials

Reagent-grade chemicals and solvents were used without additional purification. Zn(OAc)₂.2H₂0, 8-aminoquinoline (8-AMQ), Sodium dicyanamide (Nadca), and Sodium tricyanomethane (TCM) were directly purchased from Sigma-Aldrich USA Company. The solvents CH₃OH, Dichloromethane (DCM), and Acetonitrile (ACN) were obtained from SRL (Sisco Research Laboratories) Pvt. Ltd. India.

Physical Measurements

The elemental composition (CHN) was analyzed using a PerkinElmer 2400 CHN elemental instrument, while high-resolution mass spectrometry (HRMS) was conducted using a Xevo G2-XS QToF 4k instrumental model with an H-Class PLUS UPLC system. IR/Raman spectra were examined using PerkinElmer and Bruker RFS 27 instruments. NMR spectra were analyzed in DMSO-d6 solvents with a Bruker FT-NMR spectrometer. The Oxford XMX N model was used for EDX analysis, and SEM images were taken with a JEOL JSM-6390LV. UV–vis measurements were conducted using a Hitachi U-3501, and powder X-ray diffraction was performed with a BRUKER AXS model. The Thermo-Scientific NEXA analyzer was utilized for XPS spectra analysis.

Synthetic Methodology

[Zn{(8-AMQ) (dca)}₂] (1)

In a 100 mL round-bottom flask, 0.219 g of Zn(II) acetate dihydrate (1 mmol) and 0.144 g of 8-aminoquinoline (1 mmol) were dissolved in a mixture of 15 mL CH₃OH, DCM, and ACN solvents (1:1:1 molar ratio) after stirring for 30 min at a constant temperature of 65 °C on a magnetic stirrer. Then, a 5 mL methanol solution of Nadca was dropwise added and mixed after shaking in a mechanical shaker for 3 min. The solution was stirred using a magnetic stirrer for 30 min. The colorless solution was cooled, filtered, and then evaporated slowly for crystallization at room temperature. The plate-shaped single crystals suitable for SCXRD were collected and air-dried. Yield: (62%), Anal. Calc. for C₂₂H₁₆N₁₀Zn: C, 54.39; H, 3.32; N, 28.83, Found: C, 54.43; H, 3.29; N, 28.88, HRMS for complex, (m/z, TOF MS): found for 485.09 (calculated 485.82), IR (KBr cm^–1) selected bands: for ν(Nadca), 2180–2362, and for 8-AMQ, ν(N–H), 3355–3450, ν(C=C), 1615, ν(phenyl ring), 1428, 1364, for complex 1, ν(N–H), 3160, ν(C=C), 1600, ν(phenyl ring), 1410, 1340, ν(Zn–N), 585, ν(C–N–Zn), 1039, 1206, ν(dca), 2188, FT-Raman (cm^–1) selected bands: ν(C=C), 1603 s, ν(phenyl ring), 1448, 1365 s, ν(Zn–N), 584 m, ν(C–N–Zn), 1042, 1200 m, ν(dca), 2188–2238 s, ¹H NMR (DMSO-d₆, 400 MHz): δ (ppm): for 8-AMQ, 6.92–7.36 (Ar CH), 7.37 (NH₂ proton), 8.76–8.77 (Ar CH), ¹³C NMR (DMSO-d₆, 75.45 MHz): δ (ppm): For 8-AMQ, 110.15–128.93 (C Ar), 136.09–147.53 (C Ar), ¹H NMR (DMSO-d₆, 400 MHz): δ (ppm): for complex 1, 6.84–7.42 (Ar CH), 7.43 (NH₂ proton), 8.14–8.69 (Ar CH),), and ¹³C NMR (DMSO-d₆, 75.45 MHz): δ (ppm): 109.08–128.57 (C Ar), 135.94–147.04 (C Ar), UV–vis λ_max (DMF): 258 and 375 nm.

[Zn{(8-AMQ) (TCM)}₂] (2)

We employ a comparable method for synthesizing complex 2, using a 5 mL methanol solution of TCM instead of Nadca. Yield: (63%), Anal. Calc. for C₂₆H₁₆N₁₀Zn: C, 58.49; H, 3.02; N, 26.24, Found: C, 58.52; H, 3.0; N, 26.22, HRMS for complex, (m/z, TOF MS): found for 533.08 (calculated 533.88), IR (KBr cm^–1) selected bands: for ν(TCM), 2178, and for complex 2, ν(C=C), 1607, ν(phenyl ring), 1370, 1422, ν(Zn–N), 582, ν(C–N–Zn), 1075, 1242 m, ν(TCM), 2175, FT-Raman (cm^–1) selected bands: ν(C=C), 1600 s, ν(phenyl ring), 1439, 1390 s, ν(Zn–N), 582 m, ν(C–N–Zn), 1082, 1238 m, ν(TCM), 2170–2220 s, ¹H NMR (DMSO-d₆, 400 MHz): δ (ppm): for complex 2, 6.84–7.42 (Ar CH), 7.43 (NH₂ proton), 8.14–8.69 (Ar CH),), and ¹³C NMR (DMSO-d₆, 75.45 MHz): δ (ppm): 109.84–128.64 (C Ar), 136.12–147.18 (C Ar), UV–vis λ_max (DMF): 345, 265, and 220 nm.

X-ray Crystallography

Table 1 provides detailed crystallographic data and information about refining the Zn complex structures. The complexes in good-quality crystal form were grown by slowly evaporating them at room temperature from a solvent medium of CH₃OH+DCM+ACN. The crystals of the two Zn compounds were examined using a Bruker-AXS SMART APEX II diffractometer.¹⁸ with standard Mo Kα radiation. Two Zn complex structures were solved using various crystal-solving programs. SMART¹⁸ employs different approaches to collect vital crystallographic data. The software detects frames that contain data, assesses the reflections, and computes the lattice parameters. SAINT¹⁸ enhances the reflection combination, while SADABS¹⁸ corrects the absorption. SHELXTL and least-squares methods accurately determined the space group (SG), structure, and F². Complex crystal structures were examined using full-matrix least-squares methods and refined using SHELXL-2014¹⁸ and Olex-2 software.¹⁸ The crystal was refined by applying anisotropic shift parameters to all atoms. The hydrogen atoms are refined isotropically. Diamond’s software generated various molecular diagrams with crystallographic structures.

Table 1. Crystal Data and Structure Refinement for the Zn Complexes.

empirical formula	C22H16N10Zn (1)	C26H16N10Zn (2)
formula weight	485.82	533.86
temperature/K	296.15	296.15
crystal system	monoclinic	triclinic
space group	P21/c	P-1
a/Å	8.9494(19)	7.977(2)
b/Å	7.4425(16)	8.531(3)
c/Å	17.583(4)	10.000(3)
α/°	90	72.486(7)
β/°	115.609(6)	67.845(7)
γ/°	90	85.991(8)
volume/Å3	1056.1(4)	600.4(3)
Z	2	1
ρcalcg/cm3	1.528	1.477
μ/mm–1	1.197	1.060
F(000)	496.0	272.0
crystal size/mm3	0.1 × 0.06 × 0.02	0.15 × 0.06 × 0.02
radiation	MoKα (λ = 0.71073)	MoKα (λ = 0.71073)
2Θ range for data collection/°	5.048 to 50.058	4.606 to 50.918
index ranges	–10 ≤ h ≤ 10, –8 ≤ k ≤ 8, –20 ≤ l ≤ 20	–9 ≤ h ≤ 9, –10 ≤ k ≤ 10, –12 ≤ l ≤ 12
reflections collected	32,701	19,988
independent reflections	1865 [Rint = 0.1071, Rsigma = 0.0395]	2218 [Rint = 0.0814, Rsigma = 0.0444]
data/restraints/parameters	1865/0/152	2218/0/170
goodness-of-fit on F2	1.024	1.049
final R indexes [I ≥ 2σ (I)]	R1 = 0.0425, wR2 = 0.1016	R1 = 0.0364, wR2 = 0.0699
final R indexes [all data]	R1 = 0.0696, wR2 = 0.1173	R1 = 0.0548, wR2 = 0.0771
largest diff. peak/hole/e Å–3	0.44/–0.38	0.21/–0.31

Quantum Chemical Methods

The Zn complexes has been optimized using DFT/B3LYP-D3/Lanl2DZ,¹⁹ implemented in Gaussian09 software.²⁰ The graphs were generated using the Gauss View 6 package.²¹ The FMO, MEP figures were computed using the TD-DFT/B3LYP-D3 method.^22,23,7b The geometries of the Zn complexes were calculated using crystallographic coordinates and based on the theory PBE0-D3/def2-TZVP²⁴ in the Gaussian-16 program.²⁵ The electron density has been analyzed using the ″atoms-in-molecules″ (AIM)²⁶ and NCI plot²⁷ analyses using the AIM All program. The LED (Laplacian of electron density) can be broken down into contributions along the three principal axes of maximum variation.²⁸ The 3D-Hirshfeld Surface/2D fingerprint plot details were presented in ESI.

Biological Studies

Drug Preparation and % of Cytotoxicity Determination

The synthesized compounds were tested for in vitro cytotoxicity using the TBEM (Trypan Blue Exclusion Method) at various concentrations. The cytotoxicity of the test compound was evaluated based on DLA (Dalton’s Lymphoma Ascites) cells. Cells are cleaned three times using PBS (phosphate-buffered saline) or a standard cell line. The TBEM was utilized to evaluate cell viability according to standard experimental procedures. The tested sample was analyzed in triplicate.²⁹ Data were presented as the mean ± standard deviation (SD). SPSS Base 16 (SPSS Inc., Chicago, IL) and ANOVA were utilized for statistical analysis.

APDT and MIC Determination

C. albicans (ATCC 10231) was sourced from the American Type Culture Collection (ATCC, Manassas, VA, USA), and the media was purchased from Himedia, India. The antifungal activity of the synthesized compounds against C. albicans was evaluated using the WDM (Well Diffusion Method). APDT studies were conducted on 1 and 2. The testing samples underwent irradiation for 2 h utilizing a 300 W Newport Xenon arc lamp (designed irradiated samples are C1* and C2*) (where antibiotic griseofulvin, and DMSO was utilized as a negative control). The study used the well-known MBDM (Micro Broth Dilution Method) to establish the irradiated samples MIC. The fluoroprobe PBA did not show activity against the two strains in this research.³⁰

Results and Discussion

Two water-insoluble centrosymmetric mononuclear Zn complexes [Zn{(8-AMQ) (X)}₂], (X = dca/TCM) with dca (1) and TCM (2) ions were synthesized via self-assembly in situ technique (Scheme 1). Several physicochemical methods, including XPS techniques, structurally characterize the compounds. The Zn complexes with 8-AMQ ligands exhibit restricted coordination chemistry concerning X-ray crystal structures, especially in the presence of X ions (Scheme S1).^2,4,7,8 However, the literature has no information for Zn-8 AMQ complexes with X anions concerning DFT investigations, APDT, and cytotoxicity against DLA cell lines. Notably, the first time we are exploring N···Zn/H···N and weak C–H···N supramolecular interactions using QTAIM/NCI-RDG plot, crystal engineering R₄⁴ (8)/R₂²(16) synthons.

Scheme 1. Synthetic Outline for the Zn Complexes.

Structural Characterization

HRMS Analysis

The two zinc complexes feature an 8-AMQ structural frame connected by dca and TCM ions. The complexes were characterized using high-resolution mass spectroscopy (HRMS) (Figures S1–S2). The molecular ion peaks for the Zn complexes were observed at 485.09 m/z (calculated 485.82, 1) and 533.08 m/z (calculated 533.88, 2), confirming the Zn metal complexes’ stoichiometry.

IR and Raman Spectroscopy

We characterize the Zn complexes using IR and Raman spectroscopic studies (Figures S3a-c, S4a-b, and S5). The IR/Raman spectral analysis of 1 and 2 depends entirely on the stretching values of ν(N–H), ν(C=C), ν(phenyl ring), ν(Zn–N), and ν(C–N–Zn). Moreover, spacers like dca and TCM anions are joined in Zn complexes. Henceforth, IR/Raman characterization relies also on the stretching band identification of ν(dca) and ν(TCM). Before completing Zn complex structural characterization, we first need to analyze the ligands of 8-AMQ thoroughly. In 8-AMQ, stretching values of ν(N–H), ν(C=C), ν (phenyl ring) are observed at 3355–3450, 1615, 1428, 1364 cm^–1, respectively. In the case of 1 & 2, these stretching shifted values are observed at 3160, 1600, 1410, and 1340 cm^–1 (1) and 3165, 1607, 1370, 1422 cm^–1 (2), respectively.^7,8 Further, in both complexes, ν(Zn–N) and ν(C–N–Zn) values are observed at 585, 1039, 1206 cm^–1 (1) and 582, 1075, 1242 cm^–1 (2).^7,8 All these shifting IR stretching values confirm that in both Zn complexes, AMQ is present, and 8-AMQ N-donor centers are coordinated to Zn ions to form bonds Zn–N and C–N–Zn. The most exciting identification for the Zn complexes is the presence of dca and TCM. The Zn complexes’ shifting peaks near 2188, and 2175 cm^–1 confirm that the dca and TCM anions are linked to the zinc metal centers.^7b,7c,8

UV–Vis Spectrum

The UV spectra of Zn complexes were examined in DMF solvent (Figure S6). The UV spectrum of the complex’s broad peaks is observed at 258 and 375 nm (1) and 345, 265, and 220 nm (2). The results indicate that the 8-AMQ interacts with Zn²⁺ through N-donating atoms, which can be ascribed to a transition involving the π→π* aromatic benzene ring.^7b,7c The optical transition of the Zn complex is distinct from that of the Quinoline ligand because of a reduced energy of the HOMO–LUMO resulting from π overlapping of the ligands in the complex. The Zn²⁺ possesses a 3d¹⁰ arrangement, and the HOMO–LUMO orbitals of the complexes are spread out across the quinoline moiety. The characteristic of the HOMO and LUMO orbitals of the separate quinoline unit stays unchanged under the condition. This electronic transition type resembles the other Zn complexes.³¹ The peak absorption of the Zn complexes moved to a longer wavelength (nm), indicating the charge transfer from the Zn→8-AMQ (M→LCT bands).³¹

¹H and ¹³C NMR

We characterize the Zn complexes using an NMR spectral investigation (Figures S7a-b, S8a-b, and S9a-b). Therefore, the NMR analysis of 1 and 2 depends entirely on the aromatic carbon ring frame with the N-donor ligands 8-AMQ. Hence, the structural arrangements of 8-AMQ and the Zn compounds were examined based on NMR. We first did an NMR investigation for the 8-AMQ to establish the Zn complex’s structural framework. For the 8-AMQ, ¹H NMR peaks are observed at δ (ppm): 6.92–7.36 and 8.76–8.77 ppm, responsible for the Ar CH proton nature.^7b,7c A peak at δ 7.37 is identified for the NH₂ proton. Similarly, the ¹³C NMR study identified peaks as δ 110.15–128.93 ppm and δ 136.09–147.53 ppm, corresponding to the aromatic carbon. Based on 8-AMQ NMR studies, a noticeable shifting of NMR peaks is observed for the Zn complexes. For 1, Ar CH proton shifting nature δ 6.84–7.42 ppm and δ 8.14–8.69 ppm. Also, the NH₂ proton shifting is δ 7.43 ppm. In contrast, for 2, Ar CH and NH₂ proton shifting nature δ 6.84–7.42 ppm and δ 8.14–8.69 and 7.43 ppm, respectively.^7b,7c These ¹H NMR peak values confirmed that Zn complexes have an aromatic carbon ring and are coordinated with 8-AMQ N-donor centers. The shifting of ¹³C NMR peak values further substantiates both complexes’ aromatic carbon structural frames (see shifting peak values δ: 109.84–128.64 ppm and 136.12–147.18 ppm).

EDX-SEM Approach

The scanning electron microscope (SEM) is widely used to analyze the structural morphology and size of Zn complexes.³² Energy-dispersive X-ray (EDX) analysis involves using X-rays to establish the chemical composition of a synthesized material. The Zn complexes EDX spectrum (Figure S10a-b) defines the elemental and metal composition. According to the EDX profiles, it is concluded that 1 is composed of carbon (C), nitrogen (N), oxygen (O), and Na/Zn metal ions. Similarly, 2 comprises carbon (C), nitrogen (N), and Zn metal ions. The EDX information also suggests their weight percentage (Table S1). Moreover, the EDX profile confirms the interaction between Zn²⁺ ions and the N-donor 8-AMQ in the presence of dca and TCM anions. Upon examination of SEM micrographs (Figures S11a-e and S12a-e), it was found that the surface structure of the Zn complexes resembled an organized ice type. For 1, SEM graphs (a-e) divulge the ice-type morphology. Up to 10–50 μm, the ice morphology surface is rough, gradually developing more organized ice at 1 μm. The same concept applies to 2 SEM graphs (a-e). A literature study explored dramatic particle size and morphology differences from other quinoline-based metallic complexes.^31a Zn complexes were found to possess more consistent size and ice morphology characteristics, possibly due to the more substantial effect of 8-AMQ conjugation on the Zn²⁺ ion.

Powder X-ray Diffraction

The Zn complexes were analyzed using powder X-ray diffraction to determine their crystallinity by examining the X-ray powder diffraction patterns. The PXRD investigated that the Zn complexes coordinated through the N-donor atom of the 8-AMQ (Figure S13a-b) are pure in phase and have an excellent crystalline nature. The solid Zn crystals exhibited a PXRD pattern that closely resembled the simulated XRD pattern before and after deposition, indicating a successful experimental match. The results from the PXRD analysis show their concurrence. The CCDC Mercury software created the simulated pattern utilizing the single-crystal X-ray diffraction data in CIF format for the Zn complexes. The sharp diffraction peaks suggest that the synthesized Zn crystal products have high crystallinity. Further, PXRD analysis concluded that the bulk material comprises a single crystal.

X-ray Photoelectron Spectroscopy

X-ray photoelectron spectroscopy (XPS) is used to analyze the elemental composition and support the formation of two zinc complexes with 8-AMQ ligands in the presence of dca (1) and TCM (2) ions (Figure S13c-d/Table S2).^7b The successful scanning of the XPS spectrum confirms the presence of O, N, C, and Zn metal ions in the 8-AMQ complexes.³³ Concerning the X-ray crystal structure of complexes, it is clear that the Zn(II) ion is linked with the N-donor 8-AMQ along with N-bonded dca (1) and TCM (2) ions. Therefore, Zn was identified using a Zn 2p, Zn 3p, and Zn 3d XPS scan image (BE 1022,1045, 89.3, 89.2 and 11.0, 10.8 eV). The above statement further confirmed that the Zn atoms in both complexes are entirely in the Zn²⁺ form.³³ The Zn complexes XPS scan obtained binding energy corresponding to the peaks C 1s, N 1s, and O 1s are 285, 399.5, and 531 for 1, while for 2, 285, 399.2, and 531 eV, respectively.³³ The 285 eV C 1s XPS spectrum peak in both Zn complexes can be assigned to the C atoms present in the C–C bond framework.³³ Similarly, the N 1s XPS spectrum’s two peaks, at 399.5 for 1 and 2 399.2 eV, are associated with the electron-rich nitrile nitrogen in the dca and TCM ions present in the complex structures.³³ Therefore, the N 1s XPS scan identifies the formation of the dca (1) and TCM (2) complexes based on their respective binding energies (eV).

X-ray Crystal Structure Description

The X-ray single-crystal structure determination reveals that 1 crystallizes in monoclinic space group P2₁/c, while 2 crystallizes in triclinic space group P-1. The two Zn complexes are centrosymmetric and built from the isolated mononuclear moiety of [Zn{(8-AMQ) (X)}₂] where X is dicyanamide (dca) in 1, and tricyanomethane (TCM) in 2. Table 2 show the Zn complex’s significant crystallographic parameters. Figure 1 (top) presents perspective views of both complexes, while Figure 1 (bottom) represents the polymeric network of complexes. The asymmetric unit contains one ligand (8-AMQ), one metal center, Zn(II), and one coligand [(dca) in 1, and (TCM) in 2] for both complexes. The metal center, Zn (1), is hexacoordinated where the amine nitrogen’s [N (2), N(2)^a] and pyridine [N (1), N(1)^a] {^a=-X,-Y,1-Z} nitrogen’s from two aminoquinoline (AMQ) forming the basal plane in both complexes. Two nitrogen atoms, [N (3), N(3)^b] from two dicyanamide ligands in 1 and two TCM in 2 coordinated with the Zn metal centers from the axial sites, completing its coordination number and resulting in slightly distorted octahedron geometries. The Zn–N bond lengths are comparatively longer in {2.206 (3) Å in 1 and 2.298 (3) Å in 2} than in the basal site {2.137 (3) Å in 1 and 2.115 (3) Å in 2}.

Table 2. Selected Bond Lengths (Å) and Angles (°) in the Zn Complexes.

Bond lengths for Zn complexes 1 and 2
atom	atom	length/Å (1)	length/Å (2)
Zn1	N1	2.113(3)	2.126(3)
Zn1	N2	2.162(4)	2.104(2)
Zn1	N3	2.206(3)	2.298(3)

Bond angles for Zn complexes 1 and 2
atom	atom	atom	angle/°(1)	angle/°(2)
N1	Zn1	N3	89.43(15)	86.35(9)
N2	Zn1	N1	78.85(13)	79.86(9)
N2	Zn1	N3	86.46(13)	88.19(10)

Figure 1.

a-b. Perspective view of complex 1a and 2b (top) with selective atom numbering scheme. [Symmetry elements:’ = -x,1-y,1-z; * = -x, -y,1-z] (ORTEP ellipsoid probability 50%). The dashed line represents the symmetry-related part of the complex; and Polymeric network of both complexes (bottom) [Ball and stick model].

Supramolecular Interactions

Crystal packing in both Zn complexes consist of N–H···N hydrogen bond interactions. Weak C–H···N interactions are also noticed in 1. In both complexes, the amine hydrogen atoms, H2A and H2B, attached to the nitrogen atom, N (2), form intermolecular hydrogen bonds with symmetry-related nitrogen atoms from dca in 1 and TCM in 2. In 1, these hydrogen bonds form a tetramer (Figure 2). Hydrogen atom, H (1), attached to the carbon atom, C (1), also participates in a C–H···N interaction with a nitrogen atom, N (5) from a dca coligand in complex 1 (Figure 2, top). In 2, the N–H···N interactions form a hexamer like structure (Figure 2, bottom). The details of the geometric features for both complexes are presented in Tables 3-4. Both complexes exhibit π···π interactions between the planar 8-AMQ ligands. The 10-membered ring, Cg (5), of both complexes is involved in intermolecular π···π interaction with symmetry-related Cg (5) rings from nearby molecules to form a 1D structure as shown in Figures 3 (top-bottom).³³ The details of the geometric features are given in Table 5.

Figure 2.

Perspective view of intermolecular hydrogen bonding interaction in complex 1 (top), and complex 2 (bottom) with selective atom numbering scheme.

Table 3. Hydrogen Bond Distances (Å) and Angles (°) of Complex 1.

D-H···A	D-H	H···A	D···A	∠D-H···A
N(2)-H(2B)···N(5)a	0.89	2.15	3.036(5)	171
N(2)-H(2A)···N(5)b	0.89	2.15	3.024(6)	168
C(1)-H (1)···N(5)c	0.93	2.55	3.475(6)	171

D = donor; H = hydrogen; A = acceptor.

^a= x,1/2-y,1/2+z.

^b= 2-x, −1/2+y,1/2-z.

^c= x,3/2-y,1/2+z.

Table 4. Hydrogen Bond Distances (Å) and Angles (°) of Complex 2.

D-H···A	D-H	H···A	D···A	∠D-H···A
N(2)-H(2A)···N(4)a	0.89	2.19	3.070(4)	168
N(2)-H(2B)···N(5)b	0.89	2.21	3.085(4)	169

D = donor; H = hydrogen; A = acceptor.

^a= 1-x, -y, -z.

^b= −1+x, y, z.

Figure 3.

Perspective view of π···π interactions in complex 1, symmetry elements, ^a = 1-x,1-y,1-z, (top), and in complex 2, symmetry elements, ^b = -x,1-y,1-z (bottom).

Table 5. Geometric Features (Distances in Å and Angles in °) of the π···π Interactions Obtained in Both Complexes.

complex	Cg(I)···Cg (J)	Cg(I)···Perp(Å)	Cg(J)···Perp(Å)	Cg···Cg(Å)
1	Cg (5)···Cg(5)a	3.5848(15)	3.5846(15)	4.702(2)
2	Cg (5)···Cg(5)b	3.5674(10)	3.5674(10)	3.6989(19)

Cg (5) = Centre of gravity of the ring [N (2)–C (1)–C (2)–C (3)–C(4)–C(9)–C(8)-C(7)–C(6)–C (5)]. Symmetry elements.

^a= 1-x,1-y,1-z;

^b= -x,1-y,1-z. α = Dihedral angle between ring I and ring J; Cg(I)···perp = perpendicular distance of Cg(I) on ring J; Cg(I)···perp = perpendicular distance of Cg(J) on ring I.

DFT Investigations

Hirshfeld Surface and 2-D Fingerprint Plots

The Zn complexes 3D-HS and 2D-fingerprint plots are illustrated in Figures S14–15, and the Hirshfeld surface’s significant findings are submitted in Section S1.

FMO and Global Reactivity Parameters

The energy difference between the HOMO and LUMO delineated the gap energy, which serves as an indicator of the chemical and kinetic stability of the complex.³⁴ This parameter gives valuable insights into the conductivity properties and reactivity of the system. Herein, we concentrate FMO analysis on two complexes (1–2) (Figure 4). It was observed that the HOMO orbital enveloped the Zn of two ligands. Afterward, these electrons pass through the energy barrier, which is not allowed, with energies of around 3.21 and 2.73 eV. They move to the N-ring ligand (LUMO band). This finding elucidates the presence of significant electron concentrations surrounding the central metal zinc (Zn), indicating a considerable electron charge transfer phenomenon between ligands interacting with Zn. This result indicates the importance and suitability of our materials for enhancing electronic devices, as compared to the reported literature.^34d−34f Furthermore, a noteworthy outcome is the formation of donor and acceptor ligands with the same molecular framework, highlighting their potential applicability in nanoelectronic devices. Also, it was found that 2 had more conductive behavior, more excellent stability, and higher reactivity than 1. The different quantum chemical parameters are computed based on Koopman’s theorem (Table 6).

Figure 4.

HOMO–LUMO iso-surface of the Zn complexes.

Table 6. Energy Levels and Derived Quantum Chemical Parameters for Zn Complexes.

chemical parameters (eV)	1	2
Eg = εLUMO – εHOMO	3.22	2.74
IP = – εHOMO	5.98	5.73
EA = – εLUMO	2.76	2.99
	–4.36	–4.35
χ = – μ	4.36	4.35
	1.50	1.36
	6.33	6.95

DOS Profile: True Concept of Electronic Modules

The DOS spectra of the two Zn complexes are depicted in Figure 5. DOS graphs indicate that the HOMO and LUMO values demonstrate the chemical stability of the two complexes. Furthermore, these values elucidate the charge transfer mechanism and exhibit high polarizability. The low values of hardness η (1.50 and 1.36 eV) and the large electronegativity value χ (4.35 and 4.36 eV) indicate a facile transition of electrons from fundamental state to excited state, facilitating the effective formation of electronic charge transfer with the guest. These findings suggest our new synthesis system’s potential application in newly developed electronic modules. Also, this phenomenon is further corroborated by the HOMO/LUMO analysis. The significant value of ω (17.55 eV) suggests good reactivity properties of the two Zn complexes.

Figure 5.

DOS spectra of the Zn complexes.

MEP Analysis

The MEP surface is essential for elucidating Zn compounds’ chemical stability and reactivity and investigating the nucleophilic and electrophilic sites within the studied molecules.³⁵ MEP is a crucial technique for highlighting the donor and acceptor groups that enhance the stability of complexes, thereby clarifying the suitable applications of the system under investigation. Distinct color codes denote the donor and acceptor regions. Red represents the electrophilic acceptor regions (AR), while blue signifies the nucleophilic donor region (DR). The MEP iso-surfaces of the two complexes have been illustrated in Figure 6 (LHS for 1, and RHS for 2). It is observed that the acceptor regions (nucleophilic attack) are located around the Zn–C ligands. In contrast, the donor regions (electrophilic attack) are positioned to envelop the two N-ring ligands. This result suggests a significant charge transfer mechanism is taking place on the surface of the two complexes, a finding that is further corroborated by FMO analysis. Moreover, acceptor and donor regions within the same system are particularly advantageous for conductive and electronic transport materials. This discovery positions our novel synthesis system as a promising nanoelectronic application model. Additionally, the MEP is positive at the aromatic hydrogen atoms and over the π-system of the coordinated 8-aminoquinoline ring, with values ranging from 15.1 to 20.1 kcal/mol, being more positive over the pyridine ring. This MEP analysis confirms the strong propensity of the Zn-coordinated amino groups to act as hydrogen bond donors and the anionic coligands (dca/TCM), via their sp-hybridized N atoms, to serve as hydrogen bond acceptors (Figure S16).

Figure 6.

MEP iso-surface of the Zn complexes (AR: acceptor Region and DR: Donor Region).

NBO Analysis

Section S2 submitted the details fundamental principle of NBO. The Zn complexes NBO results from the second-order perturbation theory analysis of the Fock Matrix on a natural bond orbital (NBO) basis are presented in Table S3–S4 (kcal/mol). The atomic labels for both 1 and 2 are shown in Figure S17. The NBO analysis for 1 reveals significant hyper-conjugative interactions, detailed as follows: LP (2) N9 → BD* (3) (N6 - C8) (98.72 kcal/mol), LP (2) N9→ BD* (3) (N11 - C12) (56.70 kcal/mol), LP (2) N33→ BD* (3) (N30 - C32) (98.75 kcal/mol), and LP (2) N33→ BD* (3) (N35 - C36) (56.70 kcal/mol). In NBO analysis of 2, LP (1) C9→ π* (N6 - C11) (105.57 kcal/mol), LP (1) C9→ π* (N12 - C13) (61.58 kcal/mol), LP (1) C9→ π* (N20 - C21) (58.91 kcal/mol), LP (1) C35→ π* (N32 - C37) (105.58 kcal/mol), LP (1) C35→ π* (N38 - C39) (61.59 kcal/mol), and LP (1) C35→ π* (N46 - C47) (58.91 kcal/mol) interactions showed that the carbon lone pair orbitals contribute to strong resonance interactions with the adjacent π* (C≡N) antibonding orbitals. The same interactions for nitrogen-rich compounds were also previously documented in the literature.^35c These findings concluded the well-organized structure and stability of the two novel synthesis complexes, attributed to hyper-conjugative and nonbonding interactions. Furthermore, they demonstrate that 2 exhibits greater reactive and high potential charge transfer mechanism compared to 1.

QTAIM/NCI-RDG Plots. Exploration of N···Zn/H···N Interactions

Section S3 submitted the details fundamental principle of QTAIM/NCI/RDG plots. Two Zn complexes selected topological parameters based on QTAIM and NCI-RDG analyses illustrated in Table 7. The QTAIM graphs and NCI-RDG iso-surfaces have been depicted in Figure 7. The study reveals that 1 is stabilized by four N···Zn interactions formed between ligands and the central zinc metal and H···N interactions between ligands. The first interactions exhibit significant binding energies (³⁶ of approximately −16.50, −18.22, −16.43, and −18.22 kcal/mol, respectively. These findings indicate the robust stability and atomic organization of this compound, highlighting the potential electronic charge transfer occurring between the Zn and ligands, as confirmed by HOMO–LUMO analyses. The ellipticity of electron density is notably low, with values of 0.01 au and 0.03 au, further demonstrating the robust stability of these bonds with Zn, thereby contributing to the overall stability of the complex. According to Bianch et al., in the BCP2, BCP3, BCP5, and BCP6, the exceeds unity indicates the presence of hydrogen bonding interactions between N-ligands atoms and Zn metal. The appearance of a red spot in the NCI iso-surface further corroborates this. Additionally, 2 is stabilized through five interactions involving the nitrogen atoms of the ligands and the central Zn metal, along with two binds formed between nitrogen and the carbon of the ligands. In Table 5, the values of ρ(r)/∇²ρ(r) are notably elevated for BCP2, BCP3, BCP4, and BCP5, with positive values of 0.0493 au/0.1891 au, 0.0474 au/0.1739 au, 0.0475 au/0.0469 au, and 0.0493 au/0.1892, respectively. These results suggest a significant electronic charge distribution in these regions, indicative of potential strong interactions, further corroborated by MEP analysis. These bonding characteristics are exemplified by high E_int energies of −19.29, −18.51, −18.54, --19.29 kcal/mol, respectively, underscoring the stability of the complex. These bindings yield low values ranging from 0.01 au to 0.03 au, indicating well-stabilized interactions. This observation underscores the stability and atomic organization of 2. The NCI index reveals a blue spot between N and Zn, suggesting that the ligands are anchored by HB bonding. In 2, the RDG shows two blue peaks corresponding to sign(λ2) ρ equal to −0.04 au and −0.043 au, confirming the presence of hydrogen bonding interactions that are responsible for the complex stability, as corroborated by QTAIM analysis. Also, in 1 and 2, the presence of green spots between ligands indicates the formation of van der Waals forces that further enhance stabilization. A comprehensive QTAIM-NCI discussion concludes that both Zn complexes are stabilizing by hydrogen bonding and van der Waals interactions. They exhibit well-organized, symmetrical, and robust stable complexes, ideally for their selected applications.

Table 7. Topological QTAIM Parameters at Selected Bond Critical Points (BCPs).

complexes	BCPs	ρ(r)	∇2ρ(r)	G(r)	V(r)		ε(r)	Eint (kcal/mol)
(1)	1	0.0160	0.0695	0.0145	–0.0117	0.80	1.05	–3.66
	2	0.0427	0.1502	0.0416	–0.0526	1.26	0.01	-16.50
	3	0.0467	0.1777	0.0469	–0.0581	1.23	0.03	-18.22
	4	0.0160	0.0695	0.0145	–0.0117	0.80	1.05	–3.66
	5	0.0427	0.1502	0.0416	–0.0526	1.26	0.01	-16.43
	6	0.0467	0.1777	0.0469	–0.0581	1.23	0.03	-18.22
(2)	1	0.0025	0.0078	0.0014	–0.0008	0.57	0.94	–0.25
	2	0.0493	0.1891	0.0496	–0.0615	0.23	0.03	-19.29
	3	0.0474	0.1739	0.0469	–0.0590	1.25	0.01	-18.51
	4	0.0475	0.1740	0.0469	–0.0591	1.26	0.01	-18.54
	5	0.0493	0.1892	0.0496	–0.0615	1.23	0.03	-19.29
	6	0.0025	0.0078	0.0014	–0.0008	0.57	0.97	–0.25

Figure 7.

QTAIM and NCI-RDG analyses for Zn complexes.

Laplacian of electron density (∇²ρ(r)), Lagrangian kinetic energy density (G(r)), potential energy density (V(r)), ellipticity of electron density (ε(r)), and interaction energy

Supramolecular R₄⁴ (8)/R₂²(16)/ R₄⁴(16) Synthons: A New Crystal Engineering Concept

We expanded the QTAIM/NCI Plots investigation to include the analysis of new supramolecular synthons R₄⁴ (8)/R₂²(16)/R₄⁴(16) because two X-ray structures of Zn compounds showcase unique supramolecular building blocks. Partial views of Zn compounds X-ray structures explore supramolecular interactions that result in the formation of R₄⁴ (8) and R₂²(16) synthons (1), and R₂²(16)/R₄⁴(16) synthons (2). The DFT study focuses on analyzing the strong NH···N (anionic ligand) hydrogen bonds observed in the solid-state structures of 1 and 2, which are crucial for the formation of 2D supramolecular assemblies (Figure 8a-b). In 1, two symmetrically independent hydrogen bonds are formed between the hydrogen atoms of the coordinated amino groups on the 8-aminoquinoline ligand and the noncoordinated nitrogen atom of the anionic coligand, dicyanamide, with H-bond distances of approximately 2.15 Å. These interactions result in the formation of R₄⁴ (8) and R₂²(16) synthons, which drive the propagation of the Zn(II) octahedral complex into 2D assemblies (Figure 8a). Similarly, in 2, two symmetrically independent hydrogen bonds (with H-bond distances of ∼ 2.21 Å) are depicted as dashed bonds in Figure 8b. These bonds generate self-assembled dimers (denoted as A and B in Figure 8b), which correspond to R₂²(16) synthons. The alternating propagation of these synthons leads to the 2D assembly of 2 (Figure 8b), along with the formation of a fused R₄⁴(16) synthon.

Figure 8.

a-b. Partial views of the X-ray structures of compounds 1 (a) and 2 (b) Distances in Å.

Figure 9 (top) divulges the QTAIM/NCI Plot of the R₂²(16) synthon in 1. The interaction NH···N involves a bond critical point (BCP), a red sphere, and a bond path submitted as a dashed line—similarly, a blue reduced density gradient (RDG) iso-surface. The analysis indicates the presence of an additional CH···N interaction, as evidenced by a BCP, bond path, and a green RDG iso-surface. It suggests a weaker interaction compared to others. Unexpectedly, the QTAIM/NCI Plot analysis also identifies three BCPs, bond paths, and an extended RDG iso-surface connecting the dca coligands, indicating a weak van der Waals interaction, as the electron density at these BCPs is less than 0.004 au The interaction energy computed for the dimer is significant at – 29.2 kcal/mol, driven by the two strong NH···N hydrogen bonds, the weaker CH···N interaction, and the π(dca)···π(dca) stacking interaction. This vital interaction energy correlates with the large MEP values at the hydrogen bond donor and acceptor groups and reinforces the structure-directing role of the NH···N contacts. Figure 9 (bottom) presents a similar analysis for 2, focusing on the two self-assembled dimers described in Figure 9b. In dimer A, the distribution of bond critical points (BCPs), bond paths, and reduced density gradient (RDG) iso-surfaces is like that observed in 1, with blue RDG iso-surfaces characterizing the vital NH···N hydrogen bonds. Additionally, two symmetrically equivalent CH···N contacts are present, involving the CH groups ortho to the pyridinic nitrogen atom, as confirmed by the QTAIM/NCI Plot analysis. A BCP and bond path also interconnect two CN groups of the TCM anions, indicating the presence of antiparallel CN···CN contacts, which can be classified as π···π interactions, as previously demonstrated.³⁷ The interaction energy of this dimer (Figure 9a) is – 30.8 kcal/mol, comparable to the R₂²(16) synthon of 1 due to a similar combination of noncovalent interactions. Dimer B (Figure 9b) exhibits a slightly lower dimerization energy (−28.0 kcal/mol), most likely due to the absence of ancillary CH···N hydrogen bonds. Unlike in dimer A, TCM···TCM contacts are not observed. Instead, the tcm ligand of one monomer interacts with the pyridine ring of the 8-AMQ ligand in the adjacent monomer and vice versa. Two BCPs and bond paths characterize each interaction: one connects the central carbon atom of the TCM to a C atom of the Py (pyridine) ring, forming an electrostatically enhanced π···π contact. Instead, the C–H bond points toward the π-system of a CN group, consistent with a CH···π interaction. Additionally, one aromatic hydrogen atom of the pyridine ring is linked to the nitrogen atom of the tcm ligand, indicating the presence of a CH···N contact. Similar contacts involving pseudohalide ligands have been demonstrated to play a significant role in crystal engineering.^37c

Figure 9.

QTAIM (BCPs in red, bond paths as dashed bonds) and NCI Plot analysis (RDG = 0.5, ρ cutoff = 0.04 au, color range – 0.03 au ≤ (signλ₂) ρ ≤ 0.03 au, blue-green-yellow-red) of the R₂²(16) synthon of compound 1. Only intermolecular interactions are represented (top), QTAIM (BCPs in magenta, bond paths as dashed bonds) and NCI Plot analysis (RDG = 0.5, ρ cutoff = 0.04 au, color range – 0.03 au ≤ (signλ2) ρ ≤ 0.03 au, blue-green-yellow-red) of dimer A (a) and B (b) of compound 2. Only intermolecular interactions are represented (bottom).

ELF-LOL Iso-surfaces

The ELF-LOL iso-surfaces are highly selective tools for investigating electronic distribution and charge transfer phenomena within the studied Zn complex.³⁸ ELF and LOL values range from 0 to 1 and 0.0 to 0.8, respectively. An ELF value greater than 0.5 suggests the existence of bonding, nonbonding, and localized electrons, whereas a low value corresponds to electrons being delocalized. Figure 10a-d explores the 2D-ELF and 2D-LOL profiles. In both complexes, a dark red color envelopes H21 and H45 for (1) (Figure 10a-b) and H27 and H53 for (2), (Figure 10c-d) with a maximum ELF value of 1.0. The condition shows that both electrons are bonding, and electrons are not bonding in this specific region. The LOL exhibits a blue color surrounding the nitrogen and carbon atoms and the central metal Zn, highlighting the delocalization of electrons in these regions. These results suggest potential electronic charge transfer between the ligands in their interactions with the zinc, forming a donor–acceptor pair within the structure. This idea enhances the stability of each complex through hydrogen bonding, a conclusion further supported by QTAIM analyses.

Figure 10.

a-d. Zn complexes 2D-ELF and 2D-LOL analyses.

Biological Spectrum

Cytotoxic Activity

The synthesized compounds demonstrated significant cytotoxic activity against the DLA cell line.^29a Among these, the Zn salt exhibited the lowest percentage of cell death (Table 8, Figure 11a). The compounds showed varying levels of cytotoxicity at different concentrations, with C1 displaying the highest activity at lower concentrations. However, none of the synthesized compounds achieved 100% cell death at any of the concentrations tested. The data is graphically represented in Figure 11b. Using regression analysis, a linear trendline was plotted to calculate the IC₅₀. The IC₅₀ measures a substance’s effectiveness in inhibiting a specific biological or biochemical function. This indicates that the concentration needed to reach 50% inhibition of a biological process in vitro is required. In this study, the IC₅₀ was 92.53 μg/mL. The results show the percentage of cell death in the DLA cell line at drug concentrations from 12.5 μg/mL to 200 μg/mL. The compound labeled 8-AMQ displayed 3.7% inhibition of cytotoxicity at a concentration of 12.5 μg/mL, whereas the Zn salt exhibited 4.46% inhibition at the same concentration. For 8-AMQ, the percentages of cell death increased to 7.88%, 13.6%, 21.2%, 30.1%, and 37.5% at concentrations of 25, 50, 100, 150, and 200 μg/mL. The Zn salt-induced cell death rates of 12.5%, 25%, 50%, 100%, 150%, and 200% at concentrations of 4.46, 7.06, 9.53, 13.6, 17.6, and 29.6 μg/mL. C1’s cell death percentages were 19.9%, 29.5%, 40.4%, 60.4%, 68.1%, and 76.5% at concentrations of 12.5, 25, 50, 100, 150, and 200 μg/mL, respectively. The most significant cytotoxic impact occurred when C1 was administered at a 200 μg/mL concentration, leading to a 76.5% decrease in cell viability. At the same concentration, C2 showed 60.7% inhibition of cell viability. The study concludes that while all synthesized compounds are effective against DLA solid cells, C1 is the most effective, indicating its potential as a promising anticancer agent.

Table 8. (%) Cell Death after Exposure to Different Concentrations of Compounds.

	% cell death
drug concentration (μg/mL)	8-AMQ	Zn salt	C1	C2
12.5	3.7 ± 0	4.46 ± 2.1	19.9 ± 2.6	11.9 ± 1.5
25	7.88 ± 1.5	7.06 ± 1.5	29.5 ± 0.8	16.5 ± 1.7
50	13.6 ± 1.2	9.53 ± 1.6	40.4 ± 1.6	24.3 ± 2.6
100	21.2 ± 1.6	13.6 ± 0.7	60.4 ± 1.8	33.3 ± 0.6
150	30.1 ± 1.1	17.6 ± 2.8	68.1 ± 1.3	48.2 ± 1.7
200	37.5 ± 1.4	29.6 ± 2.6	76.5 ± 1.1	60.7 ± 2.7

[Control tube contains 5 dead cells, Sample dissolves in DMSO].

Figure 11.

a-b. (a) Cell death percentage (%) after exposure to different concentrations of C1-C2 and (b) Linear regression analysis for the % cell death of C1 against DLA.

Structure–Activity Relationship

The cytotoxicity results revealed a significant finding that the percentage of cell viability decreased cumulatively with increasing concentrations of the investigated complexes. The higher concentrations of the compound resulted in a decrease in the percentage of viable cells. The cytotoxicity behavior of the Zn complexes has been lucidly explained based on SAR (Structure–Activity-Relationship) governed by factors like the -NH₂ group, Zn metal, and X ions nature (X = dca (1)/TCM (2). Our synthesized complexes are mononuclear, involving -NH₂ group ligand, Zn ions in contact with X. The cytotoxicity results displayed that 1 showed greater effectiveness than 2, as evidenced by the lower percentage of cell death in the DLA cells. The role of Zn in respiration, energy metabolism, and DNA synthesis is a crucial aspect of our research, with zinc serving a structural role in these proteins.³⁹ Several metal complexes, including platinum, have been proven to hinder the growth of cancer cells. In cytotoxic activity, at least one amino (−NH₂) derivative group is essential for hydrogen bonding to DNA. The activity was linked to fewer hydrogen bonds forming between the ligands and DNA bases as the number of N–H groups in the ligands decreased. One way to modify the physicochemical properties is to change the ligands on the metal center, which can improve compound uptake.³⁹ Further, the leaving group’s nature affects toxicity; reactive leaving groups increase toxicity, while stable, poor leaving groups reduce reactivity toward DNA.³⁹ Moreover, there is a link between the electronic effects of substituent ions (X) and their cytotoxicity against DLA cell lines. In the synthesized Zn complexes, X are dca and TCM. The two ligands structurally differ mainly due to one CN additional group in TCM, which probably alters the cytotoxicity results.³⁹

Photodynamic Antifungal Therapy

APDT with the synthesized Zn complexes showed significant activity against C. albicans, as indicated by their zones of inhibition (Figure S18a-b), with increased effectiveness upon irradiation. The samples exposed to radiation, C1* and C2, exhibited a growth in zone diameter of around 15 mm concerning each strain. The results demonstrate the efficacy of our adapted drug system for photodynamic therapy (APDT)/PACT. The irradiated samples exhibited substantial activity against C. albicans, with zone diameters of 22.21 ± 1 mm for C1* and 47.20 ± 3 mm for C2*. The research revealed that the highly susceptible strains to our PDT studies resisted the antibiotic griseofulvin, demonstrating no inhibition zone against either strain. The antifungal activity mechanisms include membrane disruption, cell cycle arrest, and ROS-dependent fungal cell death. The photosensitizer (PS) in an excited state can generate highly active substances that have the potential to damage microbial cells through type-I or type-II mechanisms. The MIC values determined through PDT are listed in Table 9, with the MIC value being 2.5 μg/mL for each strain. The results are comparable to the literature published d¹⁰ complexes.⁴⁰

Table 9. Antifungal Zones of Inhibition and MIC Values of PACT.

fungal strainC. albicans	zone of inhibition ± standard deviation (mm)	MIC (μg/mL)
C1*	22.21 ± 1	2.5
C2*	47.20 ± 3	2.5

Conclusion

In conclusion, we synthesized 8-aminoquinoline-based Zn complexes with dicyanamide and tricyanomethane anions. The complexes are structurally characterized using various analytical methods, including NMR, PXRD, SCXRD, and XPS techniques. The X-ray single-crystal structure revealed that the complex crystallizes in the monoclinic and triclinic space groups, P21/c and P-1, and crystal-packing divulge N–H···N bonds as well as weak C–H···N interactions. Hirshfeld surface and fingerprint plots quantitatively ensure that complexes exhibit different supramolecular interactions, including pi···pi stacking. DFT studies confirmed that 2 has more conductivity and reactivity properties. QTAIM/NCI-RDG plot confirms N···Zn/H···N interactions and explored new supramolecular R₄⁴ (8)/R₂²(16) crystallographic synthons. The dose-dependent cytotoxicity of two Zn complexes was evaluated against the DLA cell line. The results indicated that 1 showed greater effectiveness than 2, as evidenced by the lower percentage of cell death in the DLA cells. The findings suggest that complex 1 is a potential candidate for cancer therapy. The antifungal photodynamic therapy study showed notable effectiveness against C. albicans, with 22.21 ± 1 mm and 47.20 ± 3 mm zone diameters. The article presents significant findings on the X-ray crystal structure, highlighting new supramolecular synthons and π···π stacking interactions at a large Cg···Cg distances enhance our understanding of the complex’s structural properties.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.4c09312.

• Figures for HRMS, IR/Raman, UV–vis, ¹H/¹³C NMR, PXRD, SEM, MEP, APDT experiments and graphs, Tables for EDX, and XPS spectral data, NBO calculations, Scheme for DCA/TCM bridging propensity, Hirshfeld surface and 2D fingerprint plot, NBO/QTAIM/NCI-RDG basic principle (PDF)

Accession Codes

CCDC 2379762–2379763 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: + 44 1223 336033.

Author Contributions

Suman Hazra is involved in formal analysis, research investigation, literature survey, writing review, draft editing, Graphics preparation, and software visualization. Dr. Dhrubajyoti Majumdar was the project’s author and conceived the whole research idea, performed data curation, conceptualization, methodology, research investigation, formal analysis, contributed reagents, materials, software visualization, writing review, initial draft preparation, and editing. Dr. Jessica Elizabeth Philip performed formal analysis, research investigation, biological study, and software visualization. Dr. Bouzid Gassoumi and Dr. Houcine Ghalla performed DFT experiments. Prof. Dr. A. Frontera performed DFT experiments. Dr. Sourav Roy was involved in X-ray crystallographic work. Prof. Dr. Sudipta Dalai supervises conceptualization, methodology, research investigation, and formal analysis. All authors reviewed and approved the final version of the manuscript before its submission.

The authors declare no competing financial interest.