Synthesis, spectroscopic, and lead(II) binding behavior of three novel dibenzo-18-crown-6 hydrazones

Abstract Three novel hydrazonic derivatives of dibenzo-18-crown-6 were synthesized and their vibrational and electronic absorption spectroscopic properties thoroughly investigated. Their lead binding behaviors were also characterized and the observations rationalized by density functional theoretical modeling. All three cis-dihydrazonic compounds are of low overall molecular symmetry with their ether cavity adopting an open configuration at the global energy minima where the hydrazonic side-arms are electronically and vibrationally nonequivalent. Their optical absorption features are dominated by π→π* transitions where one side of the molecule exhibits Lewis acid behavior whereas the other behaves like a Lewis base. In addition to their sensitivity to pH, all three derivatives form stable 2:1 metal-ligand complexes with lead, due to coordination at the ether cavity, in addition to the hydrazone “backbone” and possibly the heterocyclic ring. The most stable lead complex is formed with the thiophene carboxylic acid hydrazide derivative due to favorable soft-soft interactions between lead and the ring-based sulfur atom.


Introduction
Increased mining activities over the last three (3) decades due to continued advancements in technology, fueled by the growth of materials science, coupled with the increased application of various "precious" metals in such developments, has dramatically exacerbated the exposure of flora and fauna to toxic heavy metals such lead, mercury, cadmium, arsenic, chromium, copper, and others.Such species are well-known to prose seriously adverse environmental safety and human health risks; most of which are irreversible.For example, lead is a well-known neurotoxin with the ability to bioaccumulate where it is implicated in various neurological disorders [1][2][3].This toxic heavy metal which has been designated a 0 lg/L maximum contamination limit by the United States Environmental Protection Agency, is also known to persist in the environment where it provides continuous contamination of water and food sources [4][5][6].In fact, recent discoveries have revealed that in the United Kingdom, over 30% of lead present in airborne particles originate from the combustion of leaded fuels even though the use of such fuels has been outlawed for over two (2) decades [7].Of course, given the adverse human health implications associated with exposure to such toxic species, the need for simple yet accurate techniques, allowing rapid "in-the-field" detection and quantification of such, is clear.Hence, various researchers have invested significant time, resources, and research efforts, aimed at developing colorimetric and fluorometric sensors, allowing compleximetric determination of various heavy metals [8][9][10].For example, macrocyclic molecules, capable of forming host-guest complexes, such as crown ethers [11,12], calixarenes [13,14], and cryptands [15,16] have all been explored extensively for such applications, all with meaningful levels of success.However, these systems continue to suffer from sensitivity and selectivity issues.Additionally, they continue to be limited by, in some cases, narrow linear and operating pH ranges, in addition to slow response times.Fortunately, recent studies have demonstrated that benzo-crown systems have the ability to form complexes with various metals [17].Additionally, these studies have revealed that ring substitution effects are highly influential where limits of detection (LOD) and quantification (LOQ), as well as linear range (LR), are concerned [18].In some cases, such substitution even allows exo-cavity coordination, of-course, depending on the nature of the substituent.Hence, careful consideration of the substituent structure could yield tailored and improved performance of these host-guest sensing systems.For instance, the application of hydrazonic side arms/ substituents could allow improved metal binding characteristics since hydrazones are well-known to form highly stable metal complexes, exhibiting fascinating coordination geometries and topologies; features revealed by X-ray diffraction in a number of cases since they tend to form single crystals relatively easily.Hence, there exists a plethora of X-ray crystal structures of their metal complexes; a significant amount of which was reported by Bakir and coworkers [19][20][21][22].Therefore, combination of these two systems: benzo-crowns and hydrazones, could, in addition to realizing various novel compounds: "benzo-crown hydrazones," allow greater optical and or electrochemical sensitivity, selectivity, and probably even improved LR.However, to assess the usefulness of such compounds for the sensing of lead, a fundamental understanding of their spectroscopic properties (vibrational and electronic spectra), in addition to the thermodynamics of their interactions with lead, is critical.Additionally, molecular modeling, particularly density functional theory (DFT) has, and continues to, advance where both qualitative and quantitative accuracy are concerned.Indeed, these techniques have garnered tremendous experience over the years and have been found to be highly useful in aiding accurate assignment of infrared and electronic spectroscopy data [23,24] as well as in the prediction of molecular structures and energies [25][26][27].DFT methods have also been applied in elucidating the metal binding behavior of various ligand systems [28][29][30] and even in the rationale designing of optical and electrochemical sensors [31][32][33] as well as in the elucidation of entire reaction mechanisms [34,35].Other modeling methods have even been applied in the designing of drugs through in silico enzyme substrate-docking [36,37].
Hence, in this two-part exploratory study, three novel dibenzo-18-crown-6 hydrazones (DBH) are synthesized (Scheme 1) and their spectroscopic properties probed with the aim of elucidating the origins of such features from a fundamental perspective.Molecular modeling calculations, based on DFT, are applied in establishing a clear understanding of their spectroscopic features.Additionally, the thermodynamics of their interactions with lead are also investigated using various popular and well-tested methodologies.The effect of such interactions with lead on their optical and vibrational behavior is also investigated to present a highly credible coordination structure for these compounds with lead.Indeed, such knowledge of their behavior in the monomeric form will guide the development/advancement of the planned part two to this study: their electropolymerization for the preparation of highly sensitive lead Ion Selective Electrodes.

4, 4-Diformyldibenzo-18-crown-6
A mixture of dibenzo-18-crown-6 (10 mmol), trifluoroacetic acid (7 mL), and hexamethylenetetramine (10 mmol) was stirred at 90 C for 12 h after which the mixture was combined with cold water ($0 C) with vigorous stirring until an orange-brown precipitate was formed.The precipitate was then collected by vacuum filtration with washing (3 Â 30 mL of water), subsequent to which it was recrystallized from ethanol and stored in a desiccator.M.Pt.229-232 C. Yield ca.83.01%.Success of the synthesis was confirmed by 1 H and 13 C nuclear magnetic resonance (NMR) measurements (see Supplementary Information S1).

4, 4-Diformyl (fuoric-hydrazide) dibenzo-18-crown-6 (DBFH)
A mixture of 4, 4-diformyldibenzo-18-crown-6 (1 mmol), fuoric hydrazide (2 mmol), concentrated hydrochloric acid (1 drop), and absolute ethanol (25 mL) was refluxed for 15 h after which it was cooled to room temperature and then stored on ice until a brown crystalline precipitate was observed.The resulting solid was then filtered and washed thrice with cold ethanol (3 Â 5 mL), prior to being recrystallized from ethanol and dried by vacuum filtration before being stored in a desiccator.M.Pt.121-123 C. Yield ca.76.22%.Success of the synthesis was confirmed by 1 H and 13 C NMR measurements (see Supplementary Information S1).The compound was isolated as a pentahydrate as proven by elemental analysis: theory/experimental, % C: 53.18/53.64,% H: 5.86/5.09.The molecular formula of this systems was also confirmed by time of flight mass spectrometry (TOF MS) where an elemental composition of (M þ þ H) þ ¼ 633.2197 was found, compared to a theoretical mass of 632.6173 g mol À1 .
2.4.4, 4-Diformyl (nicotinic-hydrazide) dibenzo-18-crown-6 (DBNH) A mixture of 4, 4-diformyldibenzo-18-crown-6, (1 mmol), nicotinic hydrazide (2 mmol), concentrated hydrochloric acid (1 drop), and absolute ethanol (25 mL) was refluxed for 15 h after which the reaction mixture was cooled to room temperature and then kept on ice until a dark brown crystalline precipitate was formed.The solid was collected by vacuum filtration, washed thrice with cold ethanol (3 Â 5 mL) before being recrystallized from ethanol, dried at the pump, and then stored in a desiccator.M.Pt.186-188 C. Yield ca.33.90%.Success of the synthesis was confirmed by 1 H and 13 C NMR measurements (see Supplementary Information S1).The compound was isolated as a tetra-hydrate as Scheme 2. Basic synthetic scheme for the preparation of dibenzo-18-crown-6 hydrazones.TFAA (trifluoroacetic acid), HMTA (hexamethylenetetramine).It should be noted that, though the scheme suggest that only the cis derivative of compound ( 2) is formed, it is most likely that a mixture of isomers were produced; a situation with cannot be proven via spectroscopic methods.
proven by elemental analysis: Theory/experimental, % C: 56.19/56.17,% H: 8.83/5.19.The molecular formula of these systems were also confirmed by TOF MS where an elemental composition of ( 1740 was found, compared to a theoretical mass of 664.7485 g mol À1 .

Computational methods
All calculations were conducted using a Gaussian 16 software package [38].Density functional theoretical calculations were effected via the Pople-style [39] Triply split valence basis set with diffused and polarization functions on both heavy and hydrogen atoms: 6-311þþG(d,p); allowing accurate consideration for proton transfer and or long range interactions while preventing/reducing excess energy over-estimation and remaining efficient (cheap).Fermion exchange was accounted for by Becke's [40] threeparameter hybrid functional whereas Lee, Yang, and Parr's [41] model was employed for electron correlation: B3LYP.The augmented form of this functional which allows estimation of long-range interactions via a coulomb attenuating method [42] with restriction of fermion spin: RCAM-B3LYP, was also explored (vide infra).This method, benchmarked by Pereira and coworkers [43], has been shown to be highly accurate in molecular geometry and energy barrier predictions, hence, it is applied herein.

Structure optimization and infrared spectroscopy
To establish a fundamental understanding of the properties of these novel compounds, molecular modeling calculations were employed.Of course, for accurate prediction of their properties, the most probably molecular conformation: the global energy minima, was calculated for all compounds; the success of which is confirmed by the absence of negative Eigen values in the Hessian.In all cases, the molecules are nonplanar, adopting a "V" shape where the ether ring occupies the vertex of the "V" (Fig. 1).Additionally, the chains of the ether cavity adopt the low energy all-trans configuration, as is typical for chains bearing adjacent methylene groups [44,45].However, these chains, which consist of two segments (-OCH 2 CH 2 ) each, separated by an oxygen atom (y, Fig. 1), are not conformationally identical, hence, the ether cavity adopts an open configuration at the global energy minima, as calculated; a feature also reported elsewhere [18,46] for other dibenzo-18-crown-6 derivatives.
Bond angles and distances have also been calculated for all compounds, yielding tremendous agreement with experimental values.For example, the imine C ¼ N and phenyl C ¼ C distances are calculated in the ranges of 1.278-1.283and 1.398-1.414Å, respectively, but are reported, based on X-ray crystallographic and gas phase Raman studies, at 1.261 [47] and 1.392 Å [48], respectively.Such similarity between the experimental and calculated values are indicative of the high quality of the applied model chemistry.Interestingly, low symmetry in the aromatic rings bearing the ether chains is indicated by the calculated C ¼ C distances.
For instance, in the case of DBNH, the phenyl C ¼ C distances between the carbons to which oxygen "x" (Fig. 1) is attached, are calculated at 1.414 and 1.408 Å whereas the carbons attached to that bearing the hydrazone "side-arm," exhibit bond distances of 1.405 and 1.402 Å for one phenyl ring and 1.398 and 1.400 Å for the other.However, the other C ¼ C distances in these rings are between 1.390 and 1.399 Å.Indeed, similar trends are observed for all three compounds (see Supplementary Information  are calculated in the range of 1.403-1.425and 1.511-1.538Å, for all compounds, with no clear trend.However, it should be noted that, in all cases, these C-C distances are shortest for the ether chains where the CH 2 groups, separated by oxygen "y" (Fig. 1), are eclipsed.Nonetheless, the distances are typical for such bonds, as indicated by microwave spectroscopy results [49].Interestingly, the calculated order of the bond linking oxygen "x" to the phenyl ring is $1.5, in all cases, with distances in the range on 1.347-1.375Å.Such distances are largest for DBFH and shortest for DBNH.These results indicate that phenyl ring substitution might have a significant influence on the ether ring's electronics, as reported elsewhere [18].Indeed, the values calculated for DBFH are nearly identical to those for unsubstituted dibenzo-18-crown-6 (DB), indicating that the electronics of this derivative might be more similar to that for DB.For the hydrazone "back bone," which is most stable in the fully extended form, the N-N distance which is longest for DBFH is calculated in the range of 1.355-1.384Å; values which are typical for such systems, according to single crystal X-ray data [50].Interestingly, this distance is identical for both hydrazonic side arms, in all compounds.However, the calculated N-C and C ¼ O distances differ on both sides of any given compound, a clear indication of low overall molecular symmetry and probably significantly uneven electron density distribution.Indeed, calculated electrostatic potential maps (ESPM) reveal various areas of high and low electron density (Fig. 2); features discussed in greater details in the upcoming sections (vide infra).The dimensions of the heterocyclic rings, as calculated, all show marked similarities to results adduced experimentally, a clear indication that the applied modeling parameters are appropriate for the titled study.Surely, the uneven electron density in these compounds can be expected to be reflected in their spectroscopic properties, for example, their vibrational behavior.Hence, for greater understand of their fundamental properties, solid state Fouriertransform infrared (FT-IR) spectra were collected for all compounds, under ambient conditions.These spectra can be divided into two main regions: the high-frequency region of 2700 to 4000 cm À1 which is composed of the aromatic C-H stretching ( s ) vibrations ( s C-H), in addition to the imine ( s N-H) modes (Fig. 3).However, the low-frequency region of 500 to 2700 cm À1 consist of the s C ¼ N, s C ¼ C, and the s C ¼ O vibrations, in addition to the combination vibrations of the molecular finger print.The experimental spectra for all compounds consist of broad (Full Width at Half Maximum, FWHM: 93-82 cm À1 ) featureless bands in the high-frequency region.Such broadness might be due to the presence of closely spaced vibrations, caused by disruption in the vibrational degeneracy between two or more identical modes; a likely consequence of the low overall molecular symmetry of these compounds; that is, vibrations which would normally exit as single bands (Sharp) might now be split.However, if the energetic separation between these new bands is only slight, peak separation might fall below the resolution of the spectrometer, hence, the observed broadening effects.Given the complicated nature of these vibrational modes, to aid fundamental understanding of their origin, harmonic vibrational spectra are calculated for all compounds (Fig. 3b).Indeed, these calculated spectra reveal a number of sharp low-intensity bands at frequencies similar to those observed experimentally.
For instance, the bands observed at $ 2900 cm À1 which are known to be associated with the CH 2 stretching vibrations of the ether ring (Fig. 4(2)), corresponds to those calculated at $3000 cm À1 , as confirmed by vibrational animation of the calculated spectra.Indeed, such animation reveal that all bands, calculated between 2955 and 3073 cm À1 , emanate from the ether ring C-H symmetric ( ss ) and asymmetric stretching ( as ) modes.However, all segments of the ether chains vibrate at slightly different frequencies; a clear indication of disruption in the vibrational degeneracy of the CH 2 assembly due to low symmetry of the ether ring.These results confirm that the broadness of the corresponding experimental bands ($2900 cm À1 ) is the result of multiple closely spaced vibrations of the CH 2 groups.Furthermore, such observations, in addition to the similarities between the calculated and experimental spectra, also confirm that under "real-life" conditions, the ether cavity adopts an open configuration.The calculation of more bands, in addition to the lower resolution of the experimentally observed bands in this region, indicates that the symmetry of the ether chains and probably the entire molecule, is lowest for DBNH.
The phenyl ss C-H, typically observed between 3000 and 3100 cm À1 [51], is calculated as multiple broad low-intensity bands between 3204 and 3174 cm À1 , of course, the high frequency end of this region being associated with the as C-H motion.Expectedly, phenyl rings on opposing sides of the ether ring exhibit s C-H vibrations of different frequencies.Additionally, differences in the phenyl C-H environment result in different vibration frequencies for the three hydrogens attached to each ring.Unfortunately, the closeness of these bands in the experimental spectra does not allow clear identification and assignment of these vibrations, however, they are calculated at ca. 3084.7 and 3024.7 cm À1 .The imine s NC-H which is also difficult to identify in the experimental spectra are calculated at ca. 3480 cm À1 for one side of the molecule and 3479 cm À1 for the other side, for DBFH.However, in the case of DBNH, slightly greater resolution between these bands is calculated; that is, for both sides of the molecule, the calculated s N-H frequencies are at 3478 and 3475, indicating lower symmetry in this molecular region.Interestingly, this situation is more severe for DBTH; that is, the s N-H is calculated at 3607 and 3475 cm À1 .Nonetheless, these values are calculated in the expected region for N-H vibrations [52]; a testament to the quality of the applied modeling parameters.The heterocyclic ring s C-H and collective as C-H vibrations are also calculated in this region.For instance, in the case of DBNH, these vibrations are calculated between 3203 to 3160, of-course, overlapping with some of the phenyl C-H modes.However, for DBTH and DBFH, these bands are calculated in the regions of 3200 À 3258 cm À1 and 3296 À 3245 cm À1 , respectively.The broad medium band, observed in the experimental spectra, between 3300 and 3400 cm À1 (see Supplementary Information S3) indicates the presence of coordinated water molecules; a feature commonly observed for benzo-crown systems [46]; that is, at least a single water molecule is normally found coordinated to the ether cavity.However, given the additional high electron density regions present in the structures of these compounds, coordination of additional water molecules is not surprising.Indeed, combustion analysis reveal that the structure of the titled compounds is DBTH.3HThe low frequency region, as outlined in the forgoing, is composed of numerous bands, the most intense of which is the s C ¼ O vibration, observed experimentally between 1670 and 1634 cm À1 but calculated in the range of 1676 À 1664 cm À1 , for all compounds.Interestingly, both the experimental and calculated spectra reveal splitting of this band or excess broadening in some cases, indicating that the C ¼ O groups on both hydrazone side-arms are nonequivalent; a consequence of low overall molecular symmetry.Indeed, animation of the calculated spectra reveal that the C ¼ O groups, in a given compound, vibrate at slightly different frequencies.However, such disruption in the C ¼ O vibrational degeneracy is less significant for DBFH and DBTH; a clear indication that though these compounds are similar in many respects, they are energetically different.Further evidence for this proposal is provided by the calculation of the s C ¼ C vibrations as a series of twinned (split) bands between 1633 and 1534 cm À1 , ofcourse, a direct result of nonequivalence between the aromatic and heterocyclic rings; that is, both components of the calculated and observed bands represent the same vibrational mode(s) but for rings on opposite sides of the ether cavity (Fig. 5).Indeed, the experimental spectra show similar features, as expected (Fig. 5b).The other vibrations at the lower energy end of this region are derived from a combination of multiple vibrational modes.For instance, the peak calculated at 1385/1383 cm À1 but observed at 1374/1359 cm À1 in the experimental spectra, is associated with rocking of the hydrazonic N-H, C ¼ O as well as the heterocyclic ring, the NC-H and one of the ether chains.Similarly, the band calculated at 1239/1221 cm À1 but observed experimentally at 1259 cm À1 with a low energy shoulder at $1257, is associated with rocking of the phenyl rings and twisting of one segment of a single ether chain.

Absorption spectroscopy and lead binding behavior
Indeed, the aforementioned symmetry effects should also be reflected in the optical absorption properties of these compounds.Of-course, in order to investigate such effects, absorption spectra were collect for all compounds, at ambient temperature, in spectroscopy grade DMSO (Sigma 99.9%).For all three compounds, a single broad absorption (FWHM: $31 nm) is observed between ca.329 and ca.333 nm (Fig. 6).However, for DBTH, three high energy and a single low energy shoulders are obvious,  indicating that the broadness of this band is probably due to the presence of closely spaced absorptions.For DBNH, similar conclusions can be reasonably drawn, given the broadness of this main absorption at 332 nm, in addition to the presence of a weak, closely spaced absorption at $278 nm.Unfortunately, the nature (shape/structure) of these absorptions do not allow easy assignment.
Hence, time-dependent DFT (TD-DFT) calculations, using the aforementioned modeling parameters, were conducted for all compounds in DMSO.For example, the spectra for DBTH, as calculated, consist of three absorptions, one of which is observed at 358.6 nm, emanating from a single transition: HOMO to LUMO þ 1 (97.8%),due to p to p Ã electron density migration from the phenyl ring and imine linkage on one side of the ether cavity to the phenyl ring, imine pi-system, and the heterocyclic ring on the other side (Fig. 7).However, the absorption at 344.9 nm results from a single transition: HOMO-1 to LUMO (91.7%); the result of p to p Ã electron density migration on one side of the molecule.The highest energy absorption, calculated at 338.9 nm, emanates solely from the HOMO to LUMO (99.7%) transition which involves both p to p Ã and n to p Ã electron density migration from one side of the molecule (one side of the ether ring) to the other.However, the difference in the number of bands calculated versus that observed experimentally might be the result of strong solvent-solute interactions; a feature which is well-known for these compounds [53] but probably poorly mapped by the implicit solvent model, applied herein (vide supra).Nonetheless, the fact that these calculated values all fall in the absorption range of 284-371 nm; the same as that covered by the experimental band, the quality of the applied model chemistry is indicated.
Similarly, for DBFH, the lowest energy absorption is calculated at 348.2 nm due to a single transition: HOMO to LUMO þ 1 (96.7%),associated with the C ¼ C and C ¼ N p to p Ã electron density rearrangement in one phenyl ring and the attached hydrazone back bone but not the heterocyclic ring (Fig. 7).However, the band calculated at 333.7 nm; a value identical to that observed experimentally for this compound, is composed of two transitions: HOMO to LUMO (94.4%) and HOMO-1 to LUMO (5.0%); the former emanating from p to p Ã electron density migration from one side of the molecule, except the heterocyclic ring, to the pi-system and hydrazone backbone, inclusive of the heterocyclic ring, on the other side of the ether cavity.However, the latter transition involves p to p Ã electronic rearrangement on one side of the molecule.The third band, calculated at 332.9 nm, is also composed of two transitions: HOMO-1 to LUMO (90.6%) and HOMO-3 to LUMO (2.3%).Interestingly, both transitions involve electronic rearrangement on one side of the molecule; the latter being associated with electron density migration from the heterocyclic ring to the hydrazone backbone, the phenyl rings as well as the heterocyclic ring's p Ã MO, whereas the former originates from p to p Ã electron density migration on the same side of the molecule; a change which involves the hydrazonic back bone, the heterocyclic and the phenyl ring.As expected, the calculated electron density migration is similar for DBNH, as indicted by the calculated MO surfaces (Fig. 7).However, the composition of the absorptions and their normalization constants are different.For instance, the absorption at lowest energy: 335.9 nm, is composed of a single transition: HOMO to LUMO þ1 (96.3%) whereas that calculated at 324.7 nm, which is also composed of a single transition: HOMO to LUMO (99.3%), has the lowest transition dipole moment as indicated by the low oscillator strength: f ¼ 0.0014.However, the absorption at highest energy: 319.4 nm, results from a single HOMO-1 to LUMO (96.0%) transition.Based on these results, it is clear that though these compounds are similar in many respects, especially where their electronic absorption spectral features are concerned, there remains noteworthy fundamental differences between them.Hence, on addition of acid, in a titration-like manner, changes in the absorption spectral features of all compounds are different.For instance, whereas only a single isosbestic point is observed for DBFH at ca. 289 nm, two such features are formed in the spectra of DBTH (Fig. 8).In the case of DBNH, though no real isosbestic points are observed, four new bands emerged, at 232, 272, 315, and 360 nm, on addition of the first 5 lL ([HCl] ¼ 1 M) of acid.Continuous addition of acid resulted in increased intensity of the newly formed bands whereas those at lowest energy are unchanged.
For DBFH, a single isosbestic point is formed due to decreased intensity of the band at lowest energy, simultaneous with increased intensity of that at highest energy.Such dramatic changes in the absorption spectra of this compounds speaks to significant changes in its electronic structure due to interactions with H þ ions.Indeed, this is not surprising, given the number of n-electrons available on the structure of these compounds.Interestingly, though the other two compounds also consist of a similar number of n-electron sites, differences in the availability of these electrons affect their basicity/ability to interact with protons.Surely, the observed spectral changes are caused by changes in the coefficients of the molecular orbitals which are associated with these nelectron sites and or changes in the oscillator strength of the transitions involving the n-electrons.Furthermore, given that some of these bands are not transitionally pure; that is, they are composed of more than one transitions, in most cases, the effect of protonation will vary for the different bands and also the different compounds.Based on these observations, it is, therefore, reasonable to expect that their interactions with lead would also be reflected similarly by their absorption spectra.Of course, in order to investigate such effects, the absorbance spectra for all compounds were recorded after the addition of lead.Interestingly, the addition of lead result in increased intensity of the main absorbance (Fig. 8, see Supplementary Information S5), for all compounds, indicating strong metal-ligand interactions.Since, in addition to the main absorption, the shoulders also show increased intensity on addition of Pb 2þ , coordination between the hydrazone backbone, inclusive of the heterocyclic ring (s) and probably the ether ring, as is typical [18,54], is indicated.However, it should be noted that, as mentioned in the foregoing, since the bands are not composed of a single transition in some cases, coordination at one point of the structure could affect multiple bands in the spectra.Hence, experimental FT-IR spectra were collected for the lead complexes of all compounds.These IR spectra reveal significant changes in the C ¼ O vibration; that is, there is noteworthy shift to lower energy, in addition to reduced relative intensity of this vibration, indicating decreased bond order due to coordination with the metal, for all compounds.Furthermore, coalescence of the band at 1374/1359 cm À1 , ascribed to the rocking mode of the hydrazonic N-H, C ¼ O as well as the heterocyclic ring and the NC-H moiety, indicates strong interactions between Pb 2þ , the C ¼ O moiety, and the heterocyclic ring.Of course, in the cases of DBTH and DBFH where ESPM (Fig. 2) shows high relative electron density on the hydrazonic C ¼ O moiety and the heteroatom of the adjoining ring, coordination at this site is highly probably, hence, the observed changes in the infrared absorption bands.Additionally, coalescence of the C-H stretching as well as the C-H rocking combination bands indicate that the symmetry of ether cavity has been significantly modified, most likely due to coordination with the metal.This could be indicative of a metal: ligand ratio >1:1.Indeed, step-wise addition and subsequent collection of the absorbance spectra (absorbance titration), Fig. 9a, reveal two clear inflection points on a plot of absorbance versus metal: ligand ratio (Fig. 9b).These results indicate that, overall, the most stable complex between lead and these compounds, is 2:1 (metal: Ligand), however, a 1:1 complex of reasonable stability is formed prior to the 2:1 system; that is, complexation is stepwise.
Similarly, despite the low basicity of the nitrogen atom in the heterocyclic ring of DBNH, a 2:1 metal: ligand ratio is also calculated.However, given the position of the heteroatom in the heterocyclic ring, weak metal-ligand interactions, at least for one of the coordinated metal ions, is likely.Of-course, to investigate such proposals, Hill plots, as successfully applied by other authors [55,56], are applied to determine the association constants and hence, association-free energies (DG BD ) for all compounds (Table 1).Interestingly, in all cases, metal-ligand binding is exergonic, indicating that these compounds will easily form complexes with Pb 2þ .However, this value is most negative for DBTH, probably because of favorable soft-soft interactions between Pb 2þ and the large electron density of the sulfur atom of the heterocyclic ring.These results and the fact that, in all cases, metal-ligand interaction does not result in the emergence of new bands or any noteworthy changes in the energies of the original absorbance of these DB-hydrazone  derivatives, no real electron density movement between the ligand and the metal, due to coordination, is indicated.Hence, the observed spectral changes are mainly intra-ligand with the observed intensity changes being due to changes in the transition dipole moment due to changes in molecular conformation caused by metal-ligand coordination; that is, the metal plays the role of molecular conformation "modifier." For DBNH, were the least exergonic binding is calculated, reduced interactions with the heterocyclic ring due to the position of the nitrogen atom relative to the C ¼ O coordination site, is indicated.However, high electron density in the ether cavity of this compound leads to an overall similar binding energy to DBFH since the calculated DG BD represents a combination of the binding energies for both sites.Surprisingly, van't Hoff plots reveal that a net inflow of thermal energy is a pre-requisite for complexation with lead, in all cases (Table 1).However, this effect is offset by increased energy disorder (þDS) in the complex-solvent assembly.Unfortunately, numerous attempts to grow single crystals of these complexes, suitable for X-ray diffraction, were unsuccessful.Nonetheless, these results confirm that all three compounds interact strongly with lead ions, resulting in noticeable changes in their spectroscopic properties, hence, reasonable proposals for their coordination structures can be made (Scheme 3).The extent to which such strong interactions are useful is validated by the calculated LOQ and LOQ and also the LR.These analytical parameters (Table 2) reveal a reasonably low detection limit for all three compounds.
Additionally, their LRs, though not impressively wide, indicate that they could probably be applied in the detection of lead, of-course, with improved structural features that could allow a colorimetric response in the presence of this analyte.Indeed, for reallife application, their selectivity should also be probed, however, such studies are beyond this scope of this work.
However, though the aforementioned changes were not visible, changes in their electronic structure in the presence of lead and H þ , indicates that they are sensitive to their environment.Hence, they could probably find application in the preparation of modified electrodes for the detection and quantification of lead ions; the subject of "part two (2)" to this article which is currently being investigated in our laboratory.

Conclusion
Dibenzo-18-crown-6 was successfully modified to yield cis-dihydrazonic derivatives bearing two hydrazone moieties/side-arms.At the global energy minima, the ether chains of all three compounds adopt a configuration that allows the ether cavity to exit in an open arrangement.Overall, the molecular conformation of the hydrazone side arms, on either side of the ether cavity, are non-identical; a feature which is reflected in their vibrational behavior.Their optical absorption features reveal that one side of the molecule is electron-rich relative to the other which behaves like a Lewis Acid; a feature ascribed to their overall low molecular symmetry.Nonetheless, they are highly sensitive to their environment, hence, they interact strongly with acid and solute species.All three derivatives spontaneously form, in a step-wise manner, 2:1 metal-ligand complexes with lead.These complexes are formed through coordination of lead ions with both the ether cavity and heterocyclic ring of the hydrazone side arms.The results of this study indicate clearly that metal-ligand binding is strongest for the thiophene derivative due to favorable soft-soft interactions.
S2); a clear indication of low symmetry in the phenyl rings.Ether C-O-C and C-C distances

Figure 5 .
Figure 5. (a) Calculated and (b) experimental spectra for a selected sub-region of the low frequency region, exemplified by DBTH.
655.2516 was found, compared to a theoretical mass of 654.6692 g mol À1 .
The compound was isolated as a tetra-hydrate as proven by elemental analysis: Theory/ experimental, % C: 56.19/56.17,% H: 8.83/5.19.The molecular formula of these systems were also confirmed by TOF MS where an elemental composition of