Metal Complexes with Naphthalene-Based Acetic Acids as Ligands: Structure and Biological Activity

Naproxen (6–methoxy–α–methyl–2–naphthaleneacetic acid), 1–naphthylacetic acid, 2–naphthylacetic acid and 1–pyreneacetic acid are derivatives of acetic acid bearing a naphthalene-based ring. In the present review, the coordination compounds of naproxen, 1– or 2–naphthylacetato and 1–pyreneacetato ligands are discussed in regard to their structural features (nature and nuclearity of metal ions and coordination mode of ligands), their spectroscopic and physicochemical properties and their biological activities.


Introduction
Carboxylates are intriguing ligands since they may offer two carboxylato oxygen atoms to form up to four metal-oxygen bonds resulting in interesting structures. Depending on the nature of the carboxylato ligands and in combination with the choice of metal ions, the resultant metal complexes may present interesting properties from many points of view, such as magnetic, photochemical, and biological properties [1][2][3][4][5][6][7][8]. Among the carboxylato ligands, the acetato ligands and their derivatives are the most studied ones, leading to a variety of metal complexes, nuclearities and properties [7][8][9].
As a continuation of our previous perspective and review articles [10,11] concerning the structures and biological properties of metal complexes with carboxylato antimicrobial and anti-inflammatory drugs as ligands, a search of the Cambridge Crystallographic Data Centre (CCDC) database regarding the structures of metal complexes with acetato ligands was performed. Our attention was drawn by the presence of the fused polycyclic aromatic hydrocarbon ring on the acetato derivatives which gave a series of interesting metal complexes. Therefore, a thorough search of the CCDC database [12] was recorded and revealed a series of metal complexes with acetato ligands which are attached to a naphthalene or a pyrene ring (Figure 1). From the point of view of the acetato ligands, only four compounds used as ligands were found, i.e., 1-naphthylacetic acid, 2-naphthylacetic acid, naproxen and 1-pyreneacetic acid ( Figure 2).

Introduction
Carboxylates are intriguing ligands since they may offer two carboxylato oxygen atoms to form up to four metal-oxygen bonds resulting in interesting structures. Depending on the nature of the carboxylato ligands and in combination with the choice of metal ions, the resultant metal complexes may present interesting properties from many points of view, such as magnetic, photochemical, and biological properties [1][2][3][4][5][6][7][8]. Among the carboxylato ligands, the acetato ligands and their derivatives are the most studied ones, leading to a variety of metal complexes, nuclearities and properties [7][8][9].
As a continuation of our previous perspective and review articles [10,11] concerning the structures and biological properties of metal complexes with carboxylato antimicrobial and anti-inflammatory drugs as ligands, a search of the Cambridge Crystallographic Data Centre (CCDC) database regarding the structures of metal complexes with acetato ligands was performed. Our attention was drawn by the presence of the fused polycyclic aromatic hydrocarbon ring on the acetato derivatives which gave a series of interesting metal complexes. Therefore, a thorough search of the CCDC database [12] was recorded and revealed a series of metal complexes with acetato ligands which are attached to a naphthalene or a pyrene ring (Figure 1). From the point of view of the acetato ligands, only four compounds used as ligands were found, i.e., 1-naphthylacetic acid, 2-naphthylacetic acid, naproxen and 1-pyreneacetic acid ( Figure 2).
In the present review, the structural features (nature and number of metal ions, coordination mode of ligands and nature and coordination of co-ligands) and the physicochemical and spectroscopic characterization as well as the properties and potential (mainly biological) applications of the reported metal complexes of the 1-naphthylacetato, 2-naphthylacetato, 1-pyreneacetato and naproxen ligands will be presented and discussed.

General Considerations for the Acids
Naphthylacetic acids (naphthoic acids or naphthaleneacetic acids, HNA) are compounds containing a planar naphthalene ring bound to an acetic group. Based on the position of the aromatic ring where the acetic group is located, they are characterized either as 1-naphthylacetic acid (α-naphthylacetic acid, HN1A) or 2-naphthylacetic acid (β-naphthylacetic acid, HN2A) ( Figure 2). Both HNAs are white amorphous solids and are mainly used as plant growth regulators [13]. They are synthetic plant auxin hormones and are commercially used in agriculture and house-gardening as rooting agents [14]. As typical compounds of the auxin family, their use and concentration should be controlled since they may become toxic to plants at higher concentrations and to animals at lower concentrations [15]. 1-naphthylacetic acid has a more extended use than 2-naphthylacetic acid. An important advantage of 1-naphthylacetic is its stability, since, before its entrance in the tissue, it is not destructed by light or by oxidation [16]. The main actions of 1-naphthylacetic acid comprise the activation of cell division, cell elongation, photosynthesis, RNA synthesis, membrane permeability and water uptake in plants [13]. Therefore, 1-naphthylacetic acid is often used to increase the production by lowering and delaying the preharvest drop of crops and hanging fruits and improving their quality (e.g., apples, olives, oranges and hazelnuts [17,18]). Another function of both HNAs is their involvement in the formation of flower buds of tobacco [16] and pistachio plants [19]. In addition, 2-naphthylacetic acid is the main initial metabolite of anaerobic degradation of naphthalene and 2-methylnaphthalene from sulfate-producing bacteria [20].
Naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid, HNAP, Figure 2) is an established non-steroidal anti-inflammatory drug (NSAID) [21]. It is a common antiinflammatory, analgesic and antipyretic medicament and is administered for the treatment of painful dysmenorrheal [22], chronic migraine, kidney stones, rheumatoid arthritis and osteoarthritis [23]. The use of naproxen induces milder side effects regarding   osteoarthritis [23]. The use of naproxen induces milder side effects regarding increased blood pressure compared to ibuprofen [24] or celecoxib [25] and stomach ulcers compared to indomethacin [26] and other NSAIDs [27]. Naproxen may produce analgesic and antiinflammatory effects by blocking non-selectively both cyclooxygenase (COX) enzymes (COX-1 and COX-2) [28,29] and subsequently decreasing the synthesis of prostaglandins [21]. The absorption of naproxen is rapid and complete upon oral or rectal administration [21,30]. Recently, a carbon nanotube functionalized by cationic hyperbranched polyethyleneimine was examined as a potential effective carrier of naproxen [31]. 1-Pyreneacetic acid (HPYA, Figure 2) is a pyrene derivative. The pyrene ring is the smallest peri-fused polycyclic aromatic hydrocarbon [32] and, because of its 16 π-electrons [33], it may provide interesting electronic properties [34] exploitable for various applications such as the preparation of chemosensors [35]. In particular, the reaction of 1pyreneacetic acid with N-hydroxysuccinimide resulted in the formation of a Pd(II)-thioether amide chemosensor having high selectivity over Pd(0) [36]. The photoluminescence of 1-pyreneacetic acid (emission band with λmax ~400 nm, when excited at 345 nm) was also taken into consideration for the fabrication of dual-functionalized polymer nanotubes which could act as substrates for molecular probes and DNA carriers [37]. Recently, 1-pyreneacetic acid was used for the functionalization of a graphene/self-assembled monolayer modified gold electrode which could be used for the study of electron transfer of cytochrome c by electrochemical techniques [38]. 1-Pyreneacetic acid has also been proposed as a titrating reagent for the titration of organolithium and Grignard reagents [39] since the end point of such titrations is significantly accurate [40].

The Co-Ligands
Besides the four acids, i.e., 1-naphthylacetic acid, 2-naphthylacetic acid, naproxen and 1-pyreneacetic acid, used as the main ligands in the complexes under study, another thing that is significant is the role of co-ligands in these complexes, since the number of binary complexes is very limited and most of them are mixed ligand complexes. Most of the co-ligands found in the reported complexes were either O-donor ligands or N-donor ligands, and, in few cases, P-, B-or C-donors were also found.

Metal Ions of the Reported Complexes
Among the existing metal ions, a significant number of metal ions have been used to prepare coordination compounds with 1-naphthylacetato, 2-naphthylacetato, 1-pyreneacetato and naproxen ligands ( Figure 13). The common first row transition metal ions were used in the majority of the reported metal complexes, i.e., Ti(IV), Mn(II/III), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II). Coordination compounds with the second and third row transition metal ions Y(III), Ru(II/III), Ag(I), Cd(II) and Au(I) were also isolated and studied. The complexes of most lanthanide(III) ions (i.e., Pr(III), Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III) and Yb(III)) have also been found in the literature. From the s-and p-block of the periodic table, few Mg(II) and Sn(IV) compounds have also been reported.
All of these metal complexes were structurally characterized mainly using singlecrystal X-ray crystallography and some basic spectroscopic and physicochemical techniques. Most of the lanthanide(III) complexes were studied for their photochemical properties, while many transition metal complexes, especially of the NSAID naproxen, were monitored for their potential biological potency. The use of the phosphines triphenylphosphine (PPh 3 ) and tri(p-tolyl)phosphine (tptp) was also noted in some cases, while the hydrotrispyrazolylborate (Tp − ) ligand and the polydentante 1,3-diamino-2-hydroxypropane-N,N,N ,N -tetraacetic acid (H 5 dhpta) were noticed each in one structure ( Figure 12). Diverse alkyl and aryl ions such as n-butyl (n-Bu), methyl (Me) and phenyl (Ph), as well as CO, were used as carbon atom donors. The use of the phosphines triphenylphosphine (PPh3) and tri(p-tolyl)phosphine (tptp) was also noted in some cases, while the hydrotrispyrazolylborate (Tp − ) ligand and the polydentante 1,3-diamino-2-hydroxypropane-N,N,N′,N′-tetraacetic acid (H5dhpta) were noticed each in one structure ( Figure 12). Diverse alkyl and aryl ions such as n-butyl (n-Bu), methyl (Me) and phenyl (Ph), as well as CO, were used as carbon atom donors.

Metal Ions of the Reported Complexes
Among the existing metal ions, a significant number of metal ions have been used to prepare coordination compounds with 1-naphthylacetato, 2-naphthylacetato, 1-pyreneacetato and naproxen ligands ( Figure 13). The common first row transition metal ions were used in the majority of the reported metal complexes, i.e., Ti(IV), Mn(II/III), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II). Coordination compounds with the second and third row transition metal ions Y(III), Ru(II/III), Ag(I), Cd(II) and Au(I) were also isolated and studied. The complexes of most lanthanide(III) ions (i.e., Pr(III), Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III) and Yb(III)) have also been found in the literature. From the s-and p-block of the periodic table, few Mg(II) and Sn(IV) compounds have also been reported.
All of these metal complexes were structurally characterized mainly using singlecrystal X-ray crystallography and some basic spectroscopic and physicochemical techniques. Most of the lanthanide(III) complexes were studied for their photochemical properties, while many transition metal complexes, especially of the NSAID naproxen, were monitored for their potential biological potency.

Metal Ions of the Reported Complexes
Among the existing metal ions, a significant number of metal ions have been used to prepare coordination compounds with 1-naphthylacetato, 2-naphthylacetato, 1-pyreneacetato and naproxen ligands ( Figure 13). The common first row transition metal ions were used in the majority of the reported metal complexes, i.e., Ti(IV), Mn(II/III), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II). Coordination compounds with the second and third row transition metal ions Y(III), Ru(II/III), Ag(I), Cd(II) and Au(I) were also isolated and studied. The complexes of most lanthanide(III) ions (i.e., Pr(III), Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III) and Yb(III)) have also been found in the literature. From the s-and p-block of the periodic table, few Mg(II) and Sn(IV) compounds have also been reported.

Structures of the Complexes
The main features of the structures of the reported complexes are the coordi mode of the carboxylato ligands under study and the nuclearity of the resultant complexes, as well as the geometry around the central metal ions and the conne between them in the non-mononuclear compounds.
For the purposes of the present study, the reported complexes were categ based on (i) the metal nuclearity and (ii) the coordination mode of the acetato lig Most of the complexes were either mononuclear or dinuclear. Among the polyn complexes, structures for trinuclear, tetranuclear, hexanuclear and polymeric com have been reported in the literature. Considering the acetato ligands, diverse (eith or more than one) coordination modes have been observed in each complex.

Coordination of the Carboxylato Ligands
Concerning the coordination of the four acids studied herein in their coordi compounds, their carboxylate group is deprotonated. The potential coordination metal ions may be summarized to the different binding modes which are typical fo boxylato ligands, shown in Figure 14. All of these metal complexes were structurally characterized mainly using singlecrystal X-ray crystallography and some basic spectroscopic and physicochemical techniques. Most of the lanthanide(III) complexes were studied for their photochemical properties, while many transition metal complexes, especially of the NSAID naproxen, were monitored for their potential biological potency.

Structures of the Complexes
The main features of the structures of the reported complexes are the coordination mode of the carboxylato ligands under study and the nuclearity of the resultant metal complexes, as well as the geometry around the central metal ions and the connectivity between them in the non-mononuclear compounds.
For the purposes of the present study, the reported complexes were categorized based on (i) the metal nuclearity and (ii) the coordination mode of the acetato ligands. Most of the complexes were either mononuclear or dinuclear. Among the polynuclear complexes, structures for trinuclear, tetranuclear, hexanuclear and polymeric complexes have been reported in the literature. Considering the acetato ligands, diverse (either one or more than one) coordination modes have been observed in each complex.

Coordination of the Carboxylato Ligands
Concerning the coordination of the four acids studied herein in their coordination compounds, their carboxylate group is deprotonated. The potential coordination to the metal ions may be summarized to the different binding modes which are typical for carboxylato ligands, shown in Figure 14.  Figure 14H). Of the eight potential binding modes, the first six fashions (i)-(vi) were found in the crystal structures reported in the literature and will be presented in the corresponding section.
In most of the mononuclear complexes, the carboxylato group is monodentately bound to the metal ion (Table 1, part I), representative complexes are shown in Figure 15). However, in many of the reported mononuclear complexes, the carboxylato group of the ligands is bidentately chelating and coordinated to the metal ion (Table 1, part II), complexes shown representatively in Figure 16). In addition, in five complexes [42,[61][62][63][64], a combination of these two binding modes was observed; one ligand was monodentately bound and the second one was bidentately chelating and coordinated (Table 1, part III),  Figure 14H). Of the eight potential binding modes, the first six fashions (i)-(vi) were found in the crystal structures reported in the literature and will be presented in the corresponding section.
In most of the mononuclear complexes, the carboxylato group is monodentately bound to the metal ion (Table 1, part I), representative complexes are shown in Figure 15). However, in many of the reported mononuclear complexes, the carboxylato group of the ligands is bidentately chelating and coordinated to the metal ion (Table 1, part II), complexes shown representatively in Figure 16). In addition, in five complexes [42,[61][62][63][64], a combination of these two binding modes was observed; one ligand was monodentately bound and the second one was bidentately chelating and coordinated (Table 1,

II: Tridentate bridging (µ-O,O,O ) + bidentate bridging (µ-O,O ) + bidentate chelating (κ-O,O )
Regarding the bridging mode of the concerned ligands, three different bridging cases of those shown in Figure 14C Concerning the coordination mode of the carboxylato ligands in these complexes, five cases/combinations have been observed (Table 2). In many of the dinuclear complexes, the carboxylato ligands are coordinated only in a µ-O,O mode ( Figure 14D) acting as O-C-O bridges ( Table 2,  The coordination number of the metal ions varies from five to six in the case of the transition metal ions and from eight to nine in the case of the lanthanide ions, and the metal ions adapt the corresponding geometries.

Polynuclear Complexes
Few crystal structures of polynuclear metal complexes with 1-naphthylacetato, 2-naphthylacetato and naproxen ligands were reported in the literature with the number of the metal ions being three, four and six (Table 3). In all of these complexes except complex NIHVEI, these ligands have a bridging role always following the µ-O,O bidentate bridging motif (Table 3)        Considering the structural features of these seven complexes, different arrange of the metal ions were found resulting from differences in the nuclearity and the n of metal ions and co-ligands. More specifically, the three manganese ions in the co [Mn3(µ3-O)(µ2-N1A-O,O′)6(py)3] are located in a triangular arrangement with the atom in the center of the triangle [86]. In the tetranuclear copper(II) complex [C In the case of the hexanuclear titanium complex EHOGOZ, the structure could be described as a dimer of trimers of the type [Ti 3 (µ 3 -O)(µ 2 -isopropoxo) 2 (isopropoxo) 3

Polymeric Complexes
The polymeric complexes containing 1-naphthylacetato and naproxen ligands are summarized in Table 4 and may be categorized in two groups: (I) the polymeric complexes that are polymerized via the 1-naphthylacetato and naproxen ligands [41,46,59,88,[90][91][92][93] ( Table 4, part I), Figure 22) and (II) the polymeric complexes that are polymerized via other co-ligands, and the 1-naphthylacetato and naproxen ligands are just found in the coordination sphere [84,94,95] (Table 4, part II). Most of the reported polymeric complexes bear a monomeric complex as the basis of the polymer with the exception of complexes FUVZIH and CAVHOA which have a trinuclear Cd(II) and a tetranuclear Ag(I) complex, respectively, as the repeating unit of the polymeric structure.  In the first group of the complexes, where the 1-naphthylacetato and naproxen ligands are the polymerizing linkers (Table 4,   In the first group of the complexes, where the 1-naphthylacetato and naproxen ligands are the polymerizing linkers (Table 4, [46] and two bidentate µ2-O,O′ naproxen ligands which are forming bridges between the Ag(I) of the repeating tetranuclear unit in complex CAVHOA [93].

Spectroscopic and Physicochemical Characterization of the Metal Complexes
Besides the X-ray crystal structures, the reported metal complexes were also studied and characterized using various (spectroscopic and physicochemical) techniques, and their use mainly depended on the nature of the metal ion. The most often reported spectroscopic techniques are IR, NMR, photochemical (UV-vis, fluorescence), EPR and Mössbauer spectroscopies. Other techniques employed for the characterization of the complexes include thermal analysis, magnetic measurements and electrochemistry.

IR Spectroscopy
In most cases, the IR spectra of the reported complexes were discussed as a preliminary method to assess the presence, the deprotonation and the possible coordination mode of the carboxylato ligands. In the IR spectra of the complexes, two characteristic bands of the carboxylato ligands were observed: the band located in the range 1530-1645 cm −1 was attributed to the antisymmetric stretching vibration (ν asym (COO)) of the deprotonated carboxylato group, while the second band located in the region 1370-1480 cm −1 was assigned to the symmetric stretching vibration (ν sym (COO)) of the deprotonated carboxylato group (Table S1). Their difference (= ν asym (COO) − ν sym (COO)) is known as the parameter ∆ν(COO) and is often used to estimate the potential coordination mode of carboxylato ligands [96]. The ∆ν(COO) value of each complex is compared with that of the deprotonated carboxylato ligand (usually in the form of an alkali salt) and may suggest (i) a monodentate (asymmetric) coordination, if ∆ν(COO) complex > ∆ν(COO) salt or (ii) a bidentate binding mode when ∆ν(COO) complex < ∆ν(COO) salt [97]. The limits of these values often depend on the nature of the metal ion. In addition, in the case of more than one coordination mode of the ligands (e.g., monodentate and bidentate bridging), two values for ∆ν(COO) may be observed. In most cases, characteristic bands concerning the presence of the corresponding co-ligands, e.g., the out-of-plane ρ(C-H) vibrations of the respective nitrogen-donor co-ligands, have also been observed and reported [42,43,[47][48][49][50]56,[59][60][61]63,71,73,75,90,93].

NMR Spectroscopy
NMR spectroscopy was mainly applied to diamagnetic complexes, i.e., Zn(II), Ag(I) and Sn(IV) complexes. In most cases, the 1 H and 13 C NMR spectra were recorded in solutions of the complexes. In the reported 1 H and 13 C NMR spectra of Ag(I) [50,93], Zn(II) [63] and Sn(IV) [59]

with NAP ligands and of complex [Ru 2 (µ 2 -PYA-O,O ) 2 (CO) 4 (PPh 3 ) 2 ] [35]
, all of the expected signals of the NAP or PYA ligands and the respective co-ligands were present and slightly shifted downfield or upfield (compared with free HNAP or HPYA) as a result of their coordination to the metal ions. In general, the results were in good agreement with the determined crystal structures and proposed structures of the complexes. The absence of any additional signals related to other species revealed the stability of the complexes in solution.
In few cases, the 31 P or 119 Sn NMR spectra were also recorded for complexes bearing P-donor co-ligands or for tin complexes, respectively. In particular, the 31 P{ 1 H} NMR spectrum of [Ru 2 (µ 2 -PYA-O,O ) 2 (CO) 4 (PPh 3 ) 2 ] showed a signal characteristic for the PPh 3 axial ligands [35]. Especially for the Sn(IV) complexes [59], the 119 Sn NMR spectra were also recorded and gave significant information regarding the environment of Sn(IV) ions. Based on the values of the 119

Photochemical Properties
In order to study the photochemical behavior of the reported complexes, their electronic (UV-vis) and fluorescence spectra were recorded.
The UV-vis spectra of the transition metal complexes were recorded in solution and in solid state and were used to check whether the complexes retained their stability in solution and across time. In most of the reported cases, the discussion was focused on the visible area of the spectrum in order to characterize the bands assigned to d-d transitions of the centered metal ions.
Considering the photoluminescence properties of the reported complexes, the fluorescence emission spectra of complexes containing either d 10 metal ions (i.e., Zn(II) and Cd(II)) or lanthanide(III) ions were recorded with diverse excitation wavelengths.

EPR Spectroscopy
EPR spectra were recorded for few Cu(II) and Co(II) naproxen complexes in powder samples as well as in frozen solution. In general, a comparison of the EPR spectra between powder samples and solutions was useful to reveal that the complexes retained their structure in solution.
The EPR spectra of complex [Co(NAP) 2 (py) 2 (H 2 O) 2 ] were recorded in frozen DMSO solution and in powder samples which showed similar signals (a derivative centered at g = 4.8 and a broad peak at g =1.9) at low temperatures (T < 25 K) [43], typical for high-spin Co(II) ions.

Mössbauer Spectroscopy
Mössbauer spectroscopy was involved in the characterization of one Sn(IV) complex. More specifically, the 119

Thermal Behavior
The thermal behavior and stability of reported Cu(II), Zn(II), Ag(I) and Cd(II) complexes were mainly examined using thermogravimetric analysis (TGA) and differential thermogravimetric analysis (DTA). In addition, the decomposition steps were also investigated. The reported complexes were stable up to temperatures varying between 122 and 294 • C and this was followed by their decomposition up to three steps (Table 6). During these steps, the gradual loss of the ligands took place resulting in the formation of the corresponding metal oxide as the final product. In most cases, the mass losses found experimentally from the respective thermogravimetric curves were in good agreement with the theoretically calculated mass losses [45,47,48,70,84,85,87,93].

Magnetic Measurements
The magnetic properties of the paramagnetic metal complexes were often studied and reported. In most cases, especially for the mononuclear complexes, room-temperature (RT) magnetic measurements were adequate to prove their monomeric nature. For the mononuclear Co(II), Ni(II) and Cu(II) complexes as well as the dinuclear Cu(II) complexes bearing a paddlewheel arrangement of the ligands, the observed µ eff values at RT were close to the spin-only (theoretically expected) values and further variable temperature (VT) magnetic measurements were not conducted [43,49,56,61,69].
VT magnetic measurement studies were performed for a series of polynuclear manganese(II/III), iron(III), copper(II), ruthenium(III) and lanthanide(III) complexes with 1-naphthylacetato and 2-naphthylacetato ligands. For all of the reported Mn(II/III), Fe(III), Cu(II) and Ru(III) complexes, the molecular susceptibility χ M decreased upon lowering the temperature and below a temperature it increased up to a plateau value. This behavior is typical for antiferromagnetic interactions between the metal ions. The data were further fitted with appropriate equations and the corresponding g and J parameters were calculated as cited in Table 7. In all cases, the calculated parameters were in good agreement with previously reported data concerning complexes with similar structural motifs [65,66,72,86,87]. On the other hand, the VT magnetic behavior of the three lanthanide(III) complexes [Ln 2 (µ 2 -NAP-O,O ) 4 (NAP-O,O ) 2 (phen) 2 ] (Ln = Dy, Gd and Er) may be attributed to a single-molecule magnet (SMM) behavior [82].

Electrochemical Behavior
In order to study the electrochemical behavior of the complexes, the cyclic voltammograms of the complexes were recorded in solution. More specifically, the cyclic voltammograms of Mn(II/III) [86], Fe(III) [65,66] and Ru(III) [72] with 1-naphthylacetato and 2-naphthylacetato ligands and Co(II) [43], Ni(II) [61] and Cu(II) [49,55] complexes with naproxen ligands were recorded in diverse solvents and the redox potentials of the observed waves were studied.
In the case of the polynuclear complexes bearing 1-naphthylacetato or 2-naphthylacetato ligands, two distinct processes were observed: (i) the reduction and oxidation of the naphthalene moiety took place at extreme potentials providing rather quasi-reversible waves (E pc < −1.5 V, E pa > +1.0 V), while (ii) the metal-centered redox processes (M(II) ↔ M(III)) were observed at rather close-to-zero potentials resulting in quasi-reversible or irreversible waves (Table 8). In the cases of the mononuclear metal(II)-naproxen complexes, irreversible or quasireversible waves attributed to one-electron processes were observed. In all cases, the redox process [M(II)] ↔ [M(I)] was successfully assigned to E pc and E pa at potentials depending on the nature of metal ions (Table 9) [43,55,61]. were checked for potential ferroelectric properties, since they crystallized in polar space groups which is a condition for ferroelectricity [46]. The properties examined for these complexes were remnant polarization (P r ) (with values of 0.004-0.022 µC/cm 2 ), coercive field (E c ) (values of 0.077-1.04 kV/cm) and saturation spontaneous polarization (P s ) (in the range of 0.006-0.046 µC/cm 2 ); in combination with the low leakage currents (<10 −8 A/cm 2 ), these may confirm the ferroelectricity of the complexes.

Biological Activity
Many of the reported coordination compounds were screened in vitro for their potential biological activity. Therefore, the potential anticancer activity of selected complexes was monitored by determining their cytotoxicity against diverse cancer cell lines. The antibacterial activity of many complexes was tested against diverse microorganisms. The antioxidant capacity of many naproxen complexes was investigated against free radicals and via the inhibition of relevant enzymes. Few reports were found concerning other activities such as catechol oxidase-like activity and antimalarial activity. Complimentary to these studies, the interaction and the affinity of the reported complexes for certain biomacromolecules, i.e., DNA and albumins, were also evaluated in virto.
The results were expressed as the concentration that inhibits the survival of 50% of the cells (IC 50 , in µM). The reported complexes (Table 10) were more active than their components and in most cases were even more active than some of the reference com-pounds used [44,[49][50][51]62,88,90,93], which launched more elaborate studies regarding the mechanism of cancer cell death. Among the tested complexes, the most active ones were found: (i) [Mn 6 (NAP)(Hsal)(shi) 6 (py) 6 ] (IC 50     More elaborate studies concerning the potential anticancer activity of the aforementioned compounds were also conducted leading to noteworthy results. In vitro experiments concerning the combinatory activity of [Mn 6 (NAP)(Hsal)(shi) 6 (py) 6 ] with the well-known chemotherapeutic drugs irinotecan, cisplatin, paclitaxel and 5-fluorouracil against MCF-7, A549 and HeLa cell lines have shown better cytotoxic activity of each combination checked in comparison to its free components, revealing that a combination of drugs may have superior activity [90].
The association of cytotoxic effects of several reported complexes on the cancer cell lines with apoptosis was studied using diverse techniques (e.g., cell morphology studies,  [50]. The polymeric silver(I)-naproxen complex [Ag 4 (NAP) 4 (2pic) 2 ] n may also trigger early apoptosis leading to increased HT-29 cell death which is associated with mitochondrial membrane destruction [93]. The cytotoxic activity of complex [Ni(NAP) 2 (phen)(H 2 O)] may also be attributed to apoptosis as revealed by Annexin V-FITC/PI double staining studies [62].

Antibacterial Activity of the Complexes
The potential antibacterial activity of the reported compounds was evaluated in vitro against diverse microorganisms. According to the literature [48,63,73,78,83,92], the antimicrobial activity of the compounds was tested against five Gram(−) bacteria (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Salmonella typhi), seven Gram(+) bacteria (Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Listeria monocytogenes, Micrococcus luteus, Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus) and one yeast (Candida albicans). In most cases, the diameter of the inhibition zone (IZ) of the development of the microorganisms was measured for diverse concentrations of the compounds, while in fewer cases the minimum inhibitory concentration (MIC) was determined (Table S2, Supplementary Materials). In the cases of IZ measurements, a strong inhibitory effect was expected for IZ >20 mm, while IZ values in the range of 10-20 mm and <10 mm were assessed as having moderate and low antibacterial activities, respectively [83].
In the cases of MIC values, the lower the MIC values were, the better the antibacterial activity was.
In general, the antimicrobial activity of the reported Cu(II) and Zn(II) naproxen complexes was higher than free naproxen but significantly low when compared with reference compounds such as Erythromycin, Gentamycin, Vancomycin and Amphotericin B, employed in the experiments. In particular, the MIC values derived for complexes [Cu 2 (NAP) 4 (3pic) 2 ] and [Cu(NAP) 2 (H 2 O)(4pic) 2 ] were 256 µg/mL against Enterococcus faecalis and 128 µg/mL against Candida albicans, and the activity of the complexes was much lower than the respective reference compounds Vancomycin (MIC = 2 µg/mL) and Amphotericin B (MIC = 0.0625 µg/mL) [48].  (Table S2) than the reference compounds Erythromycin and Gentamycin, revealing rather low activity [63]. Similarly, the reported complexes bearing 1-naphthylacetato ligands were more active than free 1-naphthylacetic acid, but not as active as the reference compounds tested (Table S2) [73,78,83,92].

Antioxidant Activity of the Complexes
The reported coordination compounds of the NSAID naproxen were evaluated in vitro for their potential antioxidant activity. These studies included the scavenging of free radicals such as 1,1-diphenyl-picrylhydrazyl (DPPH), hydroxyl and 2,2 -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, the inhibition of the enzyme soybean lipoxygenase (LOX) and the mimicking of the enzyme superoxide dismutase (SOD).
Free radicals have unpaired electron(s) which may be transferred to neighboring molecules activating chain reactions with undesired effects in organisms such as inflammations or even cancer [101]. The antioxidant activity is often related with the donation of electrons in order to neutralize the radicals. Antioxidants are used to stop radical chain reactions either by scavenging free radicals or by inhibiting their production. The benefit of the antioxidants to organisms is the decrease in inflammations which are caused by radicalinduced damages [101]. NSAIDs such as naproxen are compounds with inflammatory activity and may obviously act as radical scavengers contributing to antioxidant activity and probably to anticancer activity [102].

Scavenging of DPPH Radicals
DPPH is a stable radical used in EPR spectroscopy [103] and as a trap to inhibit and study radical-mediated reactions in the laboratory [104]. DPPH is the most common radical used to check in vitro the radical scavenging of compounds [104]. DPPH scavengers may additionally exhibit anticancer, anti-ageing and anti-inflammatory activity and could be potential agents used for the treatment of rheumatoid arthritis and inflammation [11,105].
A series of Mn(II), Co(II), Ni(II) and Cu(II) complexes of naproxen were tested for their potency to scavenge in vitro the DPPH radicals and the results were compared with the reference compounds nordihydroguairetic acid (NDGA) and butylated hydroxytoluene (BHT). All complexes were more active DPPH scavengers than the corresponding free naproxen (Table S3). The DPPH scavenging activity of the complexes was time-independent because no significant differences in the activity were observed after 20 min and 60 min of incubation (Table S3, Figure 23) [42,43,61].
In general, the extent of the DPPH scavenging of the complexes was mostly dependent on the nature of the metal ion; among the reported naproxen complexes, the Cu(II) and Co(II) complexes exhibited relatively higher activities which were in all cases significantly lower than the activities of the reference compounds BHT and NDGA (Table S3, Figure 24). The best DPPH scavenger among the reported naproxen complexes was [Co(NAP) 2 (phen)(H 2 O) 2 ] (DPPH% = 42.42 ± 0.13%) [42,43,61]. In general, the extent of the DPPH scavenging of the complexes was mostly dependent on the nature of the metal ion; among the reported naproxen complexes, the Cu(II) and Co(II) complexes exhibited relatively higher activities which were in all cases significantly lower than the activities of the reference compounds BHT and NDGA (Table S3, Figure 24). The best DPPH scavenger among the reported naproxen complexes was [Co(NAP)2(phen)(H2O)2] (DPPH% = 42.42 ± 0.13%) [42,43,61].  In general, the extent of the DPPH scavenging of the complexes was mostly dependent on the nature of the metal ion; among the reported naproxen complexes, the Cu(II) and Co(II) complexes exhibited relatively higher activities which were in all cases significantly lower than the activities of the reference compounds BHT and NDGA (Table S3, Figure 24). The best DPPH scavenger among the reported naproxen complexes was [Co(NAP)2(phen)(H2O)2] (DPPH% = 42.42 ± 0.13%) [42,43,61].  The co-ligands (i.e., their existence and their nature) do not seem to influence the activity of the complexes against DPPH radicals which are rather low. In conclusion, the DPPH scavenging activity of the reported metal-naproxen complexes is generally low or, in few cases, moderate.

Scavenging of Hydroxyl Radicals
Hydroxyl radicals are very active radicals and may launch successive radical reactions leading to the production of the dangerous reactive oxygen species (ROS) which may induce damages to tissues and inflammations. Therefore, they bear a significant role in radical chemistry, although they have a rather short life. However, compounds that can initially inhibit these successive ROS reactions by scavenging hydroxyl radicals may prove to be important antioxidant factors [11,106].
The ability of Mn(II), Co(II), Ni(II) and Cu(II) complexes of naproxen to scavenge hydroxyl radicals was evaluated in vitro and compared with the reference compound 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (trolox). Almost all of the reported complexes exhibited very high hydroxyl scavenging activity which was even higher than the reference compound trolox ( Figure 25 and Table S4). Most of the reported complexes were better scavengers of hydroxyl radicals than free naproxen ( Figure 25) [42,43,61].
Hydroxyl radicals are very active radicals and may launch successive tions leading to the production of the dangerous reactive oxygen species may induce damages to tissues and inflammations. Therefore, they bear a s in radical chemistry, although they have a rather short life. However, compo initially inhibit these successive ROS reactions by scavenging hydroxyl prove to be important antioxidant factors [11,106].

ABTS Radical Scavenging
The cationic radical of ABTS can often react with antioxidants [107] and is used as a marker of the antioxidant capacity of foods [108] and the total antioxidant activity of radical scavengers [109]. Within context, the ability of the compounds to scavenge ABTS radicals is often determined as a supplementary experiment to hydroxyl and DPPH radicals [11] and is compared with the reference compound trolox.
The in vitro ABTS scavenging ability of Mn(II), Co(II), Ni(II) and Cu(II) complexes of naproxen was reported and the results are summarized in Table S5 and in Figure 26. Many of the complexes were significantly active towards ABTS radicals and were more potent than the reference compound trolox. Among the reported complexes, the best ABTS scavengers ( Figure 26 olecules 2023, 28, 2171

ABTS Radical Scavenging
The cationic radical of ABTS can often react with antioxidants [107] an marker of the antioxidant capacity of foods [108] and the total antioxidant a ical scavengers [109]. Within context, the ability of the compounds to scaven icals is often determined as a supplementary experiment to hydroxyl and D [11] and is compared with the reference compound trolox.
The in vitro ABTS scavenging ability of Mn(II), Co(II), Ni(II) and Cu(II) naproxen was reported and the results are summarized in Table S5

LOX Inhibitory Activity of the Complexes
LOX is the enzyme involved in a procedure occurring via carbon-cen (lipoxygenation) [110]. The inhibition of LOX activity is often related with

LOX Inhibitory Activity of the Complexes
LOX is the enzyme involved in a procedure occurring via carbon-centered radicals (lipoxygenation) [110]. The inhibition of LOX activity is often related with total antioxidant activity and free radical scavenging [111]. The ability of naproxen and its Ni(II) and Ag(I) complexes [50,61] to inhibit the activity of LOX was expressed as the concentration of the compound that inhibits the activity of the enzyme by 50% (IC 50 ) and was compared to the reference compounds caffeic acid and cisplatin (Table S6).
All of the Ni(II) and Ag(I) complexes tested were better LOX-inhibitors than free naproxen and especially than the reference compounds used in each case ( Figure 27). Among the complexes tested, the silver(I) complexes were the most potent compounds with [Ag(NAP)(PPh 3   SOD is the enzyme that scavenges superoxide radicals and tra gen and H2O2. Among the proposed mechanisms of anti-inflamm NSAIDs, the inhibition of the generation of superoxide radicals [11 of superoxide anions produced by nucleophiles [113] have also SOD-like activity was reported for two Cu(II)-naproxen complexe reported complexes [Cu2(NAP)4]n and [Cu(NAP)2(3pym)2]n displa like activity which was comparable to that of the enzyme [114].

SOD-like Activity of the Complexes
SOD is the enzyme that scavenges superoxide radicals and transforms them to oxygen and H 2 O 2 . Among the proposed mechanisms of anti-inflammatory activity of the NSAIDs, the inhibition of the generation of superoxide radicals [112] and the elimination of superoxide anions produced by nucleophiles [113] have also been considered. The SOD-like activity was reported for two Cu(II)-naproxen complexes ( Table 11). The two reported complexes [Cu 2 (NAP) 4 ] n and [Cu(NAP) 2 (3pym) 2 ] n displayed significant SOD-like activity which was comparable to that of the enzyme [114]. Table 11. SOD-like activity (IC 50 , in µM) of reported Cu(II)-naproxen complexes.

Other Biological Activities
Other biological activities monitored for selected metal complexes include the catechol oxidase-like activity, the antimalarial activity and the reaction with linoleic acid.
A series of Zn(II)-naproxen complexes were checked for their in vitro antimalarial potency [63]. More specifically, six Zn(II)-naproxen complexes were monitored for the inhibition of the in vitro formation of β-hematin and the mononuclear complexes [Zn(NAP) 2 (phen)] and [Zn(NAP) 2 (neoc)], which both bear a phenanthroline-based coligand, and were the only active compounds. In particular, complex [Zn(NAP) 2 (neoc)] was the most active among the tested complexes, showing an important inhibition of β-hematin formation in rather low concentrations (in the range 0.6-1 mg/mL) with efficacy > 75% which is comparable with the reference compounds Chloroquine and Amodiaquine [63].
The influence of complex [(n-Bu) 2 Sn(NAP) 2 ] upon the peroxidation of linoleic acid was also monitored. The interaction of the complex with linoleic acid (an essential component of the cell membrane) resulted in increased amounts of hydroperoxylinoleic acid. Such a reaction could either decrease the quantity of linoleic acid in the cell membrane or even totally remove it from the membrane leading to serious damage and dysfunction of the membrane, which is important in the case of cytotoxicity studies [60].

Interaction of the Compounds with Biomacromolecules
Complimentary with biological activity studies, the interaction of bioactive compounds with biomacromolecules is often studied in order to evaluate the biological potency of the compounds and to check possible mechanistic pathways or biological targets. Overall, the most commonly studied biomacromolecules are DNA and albumins.

Interaction of the Reported Complexes with DNA
DNA is among the biomolecular targets for a series of drugs including antibacterial, antiviral and anticancer agents [115], because it can regulate genetic information and may affect the replication of the cell and the protein expression. DNA is involved in diverse mechanisms of action for such drugs, e.g., drugs such as methotrexate inhibit the nucleotide synthesis, others such as doxorubicin inhibit the activity of the topoisomerase enzyme and Pt-based drugs may intervene in double-strand DNA, further blocking its replication [116]. Metal-based drugs with labile ligands (e.g., cisplatin) may bind covalently to DNA bases via vacant coordination sites [117], while those containing non-labile ligands remain stable and may interact noncovalently with DNA by intercalation, groove-binding and/or electrostatic interaction [117,118]. In addition, the cleavage of DNA may also be a result of its interaction with metal complexes being able to act as chemical nucleases [118] and may occur simultaneously with tight DNA binding [119,120]. With DNA being a possible target of photodynamic therapy, the changes in the DNA helix induced by irradiation in the presence of metal complexes are also interesting to study [121][122][123].
Considering the reported metal complexes with the considered ligands, many metalnaproxen complexes have been studied for their interaction with calf thymus (CT) DNA, which is the most common form of linear DNA studied. The interaction of the complexes with CT DNA was studied using diverse techniques (UV-vis spectroscopy, cyclic voltammetry, viscosity measurements and fluorescence emission spectroscopy) aiming to determine the mode of this interaction and to calculate the DNA-binding constants (K b ). Most of the reported metal-naproxen complexes were proposed to interact with CT DNA by intercalation [42,43,49,50,56,60,61,90], i.e., via insertion of the aromatic ligands in between the DNA nucleobases which are further stabilized by the development of π-π stacking interactions.
The DNA-binding constants of the reported complexes were calculated using the Wolfe-Shimer equation [124] and their values are summarized in Table S7. The K b values of the reported complexes were found in the range of 10 4 -10 6 M −1 , revealing a tight interaction with CT DNA. Most of the complexes were found to be tighter DNA binders than the classic DNA intercalator ethidium bromide (EB) (K b = 1.23 × 10 5 M −1 ) [125]. This fact was important for the employment of EB competitive displacement studies which were used to confirm the intercalative interaction with DNA. On the basis of K b values (Table S7, Figure 28), the Ni(II) complexes were found to be the tightest DNA binders with all K b values being higher than 10 5 M 1 [61], while the highest K b value was reported for complex [Mn(NAP) 2 (phen)(H 2 O)] (K b = 6.40 × 10 6 M −1 ) [42].
Molecules 2023, 28, 2171   [60], and the theoretical results were found to be in good agreement with the experimental findings regarding the mode of interaction and the relative affinity of the DNA interaction.

Interaction of the Reported Complexes with Albumins
Serum albumin (SA) is a multifunctional protein in blood serum. Its abundance is related with its important biological role, since it is responsible for the acid-base equilibrium in organisms, for the maintenance of osmotic pressure in blood and for the transportation of small molecules of hormones, fatty acids, ions and drugs through the bloodstream [126,127]. Additionally, albumins also have antioxidant and anticoagulant properties which are taken into consideration for potential clinical and pharmaceutical biochemical applications [128,129]. The most commonly studied albumins are human serum albumin (HSA) and its homolog-bovine serum albumin (BSA). The structures of both albumins have been characterized by crystallography. Their three domains (I, II and III) are divided in two subdomains (A and B) [130]. Sudlow's site 1 (or drug site I) in subdomain IIA and Sudlow's site 2 (or drug site II) in subdomain IIIA are the most important sites to host drugs and metal ions [130]. The intense fluorescence emission bands observed for both albumins, when their solutions are excited at 295 nm, are attributed to the presence of tryptophan residues; HSA has one tryptophan residue at position 214 and BSA has two tryptophans at positions 134 and 212 [130,131].
The interaction of the reported metal-naproxen complexes with both albumins was monitored by fluorescence emission quenching titrations [42,43,56,61,90]. The observed quenching was an indication of the noncovalent interaction of the compounds with the albumins [132]. The SA quenching constants (k q ) were calculated using the Stern-Volmer equation and plots [133]. The k q values of the reported compounds for both albumins (Tables S8 and S9) are significantly higher than the value of 10 10 M −1 s −1 , suggesting the existence of a static quenching mechanism [134], which is confirmation of the noncovalent interaction of the compounds with the albumins. Among the reported complexes, the Ni(II)-naproxen complexes presented the highest k q values for both albumins (Figure 29) [61].
The SA-binding constants (K) of the reported complexes were determined using the Scatchard equation and respective plots [133]. The K values of the reported compounds for both albumins (Tables S8 and S9) are higher than that of free naproxen and are of the 10 4 -10 6 M −1 magnitude [42,43,56,61,90]. These values are indicative of tight binding to both albumins which may be considered reversible, when compared with the highest noncovalent binding constant of value 10 15 M −1 [135]. This reversible binding may allow the release of the bioactive compounds when approaching their biological targets. Among the reported complexes, the manganese(II)-naproxen complexes presented the highest K values for both albumins (Figure 30), i.e., [Mn(NAP) 2 (CH 3 OH)] n for BSA [90] and [Mn(NAP) 2 (py) 2 (H 2 O) 2 ] for HSA [42].

Conclusions and Perspectives
As shown in the discussion, the presence of naproxen, 1-naphthylacetato, 2-naphthylacetato and 1-pyreneacetato ligands has generated a lot of interesting complexes concerning their structures and their photochemical and in vitro biological properties. The characterization of the complexes was achieved using X-ray crystallography and diverse physicochemical and spectroscopic techniques.
Among the metal ions participating in these complexes, most of them belong either to the first row transition metals (Ti(IV), Mn(II/III), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II)) or to lanthanides (Pr(III), Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III) and Yb(III)). Of course, there are some metal ions from second and third row transition metals (Y(III), Ru(II/III), Ag(I), Cd(II) and Au(I)) as well as from the s-block (Mg(II)) and p-block (Sn(IV)) of the periodic table. Indeed, the number of so-far-reported metal ions participating in such complexes is significant, leaving, however, opportunities and perspectives for the remaining transition metal ions that could also be taken into consideration for the formation of novel coordination compounds. The role and number of the co-ligands are important, since they contribute to the stabilization of the complexes and may offer, in most cases, synergism in the reported biological properties. Most of the co-ligands are oxygen-donors or heterocyclic nitrogen-donors.
Considering the nuclearity of the reported coordination compounds, most of them are mononuclear and dinuclear complexes. A few examples of trinuclear, tetranuclear and hexanuclear complexes have also been reported, where the ligands under study have mainly played an important bridging role. The reported polymeric complexes could be categorized to those owing their polymeric structure to bridges formed by the ligands under study and to compounds where naphthylacetato and naproxen ligands are terminal and do not contribute to the polymeric nature of the compounds.
The naproxen, 1-naphthylacetato, 2-naphthylacetato and 1-pyreneacetato ligands have been found in diverse coordination modes, either in one discrete mode or in a combination of two or even three different fashions. Monodentate and bidentate chelating modes and their combination were observed in the cases of mononuclear complexes. In the case of dinuclear, polynuclear and polymeric complexes, the concerned ligands were found in the bidentate Among the physicochemical and spectroscopic techniques used, IR spectroscopy provided information regarding the coordination mode of the carboxylato ligands and the co-ligands. NMR, EPR and Mössbauer spectroscopies were also employed in cases where the nature of the metal ions allowed for their application. The photochemical properties of the complexes were focused on the study of the UV-vis spectra and the photoluminescence properties. The role and the choice of the naphthalene ring were crucial for these properties since the fluorescence properties of the transition metal complexes were assigned to intraligand π-π* transitions, while, for the lanthanide(III) complexes, they were attributed to f-f transitions. Thermogravimetric studies, magnetic measurements and cyclic voltammetry studies revealed their thermal, magnetic and electrochemical behavior, respectively.
The potential biological properties of selected reported complexes are significant. Selected complexes showed in vitro noteworthy cytotoxic potency towards diverse cancer cell lines which, in most cases, were even better than the reference compounds employed. The reported studies concerning the possible mechanism of cytotoxicity presented by selected complexes revealed their ability to induce apoptosis on studied cancer cell lines. The in vitro antibacterial activity of the selected complexes was evaluated against diverse microorganisms. The in vitro antioxidant activity of naproxen complexes was examined regarding free radical scavenging, the inhibition of the LOX enzyme and the SOD-like activity of selected compounds, and revealed their antioxidant potency. In addition, there are unique reports concerning the catalytic oxidation of 3,5-di-tert-butylcatechol to 3,5-di-tertbutylquinone, the in vitro antimalarial potency of a series of Zn(II)-naproxen complexes and the influence of a Sn(IV)-naproxen complex upon the peroxidation of linoleic acid. The interaction and affinity of selected naproxen complexes with CT DNA and serum albumins were studied in the context of their influence on biomacromolecules. All of these data have revealed the potential biological relevance of the so-far-reported coordination compounds of naproxen and 1-or 2-naphthylacetato ligands and may open novel pathways regarding biological activities and mechanisms.
In conclusion, naproxen, 1-naphthylacetic acid, 2-naphthylacetic and 1-pyreneacetic acid may serve as interesting ligands in their coordination compounds as their binding to metal ions has resulted in diverse interesting structures bearing noteworthy spectroscopic, magnetic and biological properties. The research concerning these ligands and possible derivatives may be focused on the use of unexplored metal ions for novel complexes, the formation of novel organic derivatives that may serve as ligands in future complexes by introducing modification in the naphthalene or pyrene rings and the in-depth investigation of the reported properties in order to explore potential mechanistic pathways and to reveal differentiated activities using more elaborate experimental and theoretical studies.

Conflicts of Interest:
The authors declare no conflict of interest.