Design and Modulation of Selectivity toward Vanadium(V) and Uranium(VI) Ions: Coordination Properties and Affinity of Hydroxylamino-Triazine Siderophores

Based on the strong binding and high selectivity properties of 2,6-bis[hydroxy(methyl)amino]-4-morpholino-1,3,5-triazine (H2bihyat) for [UVIO2]2+, novel binucleating ligands (BLs) N,N′,N″,N‴-((1,4-phenylenebis(oxy))bis(1,3,5-triazine-6,2,4-triyl))tetrakis(N-methylhydroxylamine) (H4qtn), N1,N4-bis(4,6-bis(hydroxy(methyl)amino)-1,3,5-triazin-2-yl)benzene-1,4-diamine (H4pdl), and N1,N2-bis(4,6-bis(hydroxy(methyl)amino)-1,3,5-triazin-2-yl)ethane-1,2-diamine (H4enl) were synthesized. Binuclear complexes formed by coordination of hard metal ions with H4qtn are thermodynamically more stable than their mononuclear analogues with H2bihyat due to the increase in entropy accompanying the formation of more chelate rings. Reaction of either H4qtn or H4pdl or H4enl with [UVIO2]2+ and [VVO2]+ resulted in the isolation of the binuclear complexes [(UVIO2)2(μ-qtn)(H2O)4] (1), [(VVO2)2(μ-qtn)][PPh4]2[PPh4] (2), [(UVIO2)2(μ-pdl)(H2O)2(MeOH)2] (3), [(VVO2)2(μ-pdl)][PPh4]2 (4), [(UVIO2)2(μ-enl)(H2O)4] (5), and [(VVO2)2(μ-enl)][PPh4]2 (6). The binuclear complexes 1–6 were characterized by single-crystal X-ray diffraction analysis in solid state and by NMR and ESI-MS in solution. The comparison of the coordination ability of the BLs with either pyridine-2,6-dicarboxylic acid (H2dipic) or H2bihyat or CO32– toward [UVIO2]2+ and [VVO2]+ was investigated by NMR and UV–vis spectroscopies and DFT theoretical calculations, revealing a superior performance of BLs. The selectivity of the BLs for [UVIO2]2+ over [VVO2]+ is decreased compared to that of H2bihyat but increases considerably at pH > 9 values. Formation of the mixed-metal binuclear species [UVIO2(μ-O)VVO2] influences the selectivity and dynamics of the reaction of H4qtn for [UVIO2]2+ and [VVO2]+ in aqueous solution. The results of this study provide crucial information for the ligand design and the development of stronger and more selective systems.


■ INTRODUCTION
−39 In order to improve the ligands' selectivity for binding [U VI O 2 ] 2+ , the chelating group has to satisfy the soft−hard acid−base properties and the geometric preferences of the metal ion.The equatorial plane of [U VI O 2 ] 2+ is the only one available for coordination, meaning that planar, penta-, or hexadentate hard-donor ligands fulfill the ligation requirements for selective binding of [U VI O 2 ] 2+ (Schemes 1 and 2). 26−14,40−42 The high thermodynamic stability of the hard metal ion complexes with BHT siderophores has been attributed to the hard hydroxylamine oxygen and the negative formal charge of the triazine nitrogen donor atoms.The tridentate planar BHT ligands fit perfectly in the equatorial plane of [U VI O 2 ] 2+ , thus satisfying the geometric requirement of [U VI O 2 ] 2+ for its selective binding.Recently, the thermodynamic stability and selectivity for [U VI O 2 ] 2+ over Fe III and [V V O 2 ] + with the BHT ligand, 2,6bis[hydroxy(methyl)amino]-4-morpholino1,3,5-triazine (H 2 bihyat; Scheme 2) have been reported. 13The selectivity and thermodynamic stability of H 2 bihyat for [U VI O 2 ] 2+ were found to be superior in comparison with other hard-donor ligands, such as pyridine-2,6-dicarboxylic acid (H 2 dipic; Scheme 2) and amidoxime (H 3 pidiox, Scheme 2), dictating BHT ligands as the best candidates for sequestration of [U VI O 2 ] 2+ from the sea.
Herein, we report the synthesis of the binucleating BHT-type ligands (BLs), N,N′,N″,N‴-( (1,4-phenylenebis(oxy))bis (1,3,5-triazine-6,2,4-triyl))tetrakis(N-methylhydroxylamine) (H 4 qtn), N 1 ,N 4 -bis(4,6-bis(hydroxy(methyl)amino)-1,3,5-triazin-2-yl)benzene-1,4-diamine (H 4 pdl), and N 1 ,N 2 -bis(4,6-bis(hydroxy-(methyl)amino)-1,3,5-triazin-2-yl)ethane-1,2-diamine (H 4 enl) (Scheme 2) and the syntheses and structural and solution characterizations of six new binuclear uranyl and vanadate( (4), [(U VI O 2 ) 2 (μ-enl)(H 2 O) 4 ] (5), and [(V V O 2 ) 2 (μ-enl)][PPh 4 ] 2 (6).The BLs have been designed to favor the binding of the metal ions by increasing the entropy of the system through the formation of more chelate rings than H 2 bihyat.By increasing the nucleating sites from one to two, although far less than the multiple binding sites in a polymeric material, we mimic a polymer better, keeping the compounds small and easier to study.Thus, the information that will be obtained from the interaction of BLs with the metal ions will give us a better insight of how to make the polymeric materials used for the selective binding of metal ions more effective.In addition, the bridging moieties have been chosen to be either aliphatic so that the two metal ions are isolated or aromatic so that the two metal ions might interact with each other controlling the thermodynamic stability of the complexes.The BLs are of the strongest binders for [U VI O 2 ] 2+ and [V V O 2 ] + , to be reported.The selectivity of BLs for [U VI O 2 ] 2+ and [V V O 2 ] + is pHdependent, and the equilibrium is shifted toward [U VI O 2 ] 2+ at high pHs (>7).However, in aqueous solution, the reaction of [U VI O 2 ] 2+ and [V V O 2 ] + with BLs results in the formation of 1−6 and [(U VI O 2 )(V V O 2 )(μ-BL)(H 2 O) 2 ] − and U VI −μ-O−V V species which influence the selectivity and kinetics of the reactions.
7.46 (s, 4H, C 6 H 4 ), 3.33 (s, 12 H N−CH 3 ); 13   O (0.0100 g, 0.020 mmol) and triethylamine (6.0 μL, 0.040 mmol) to a stirred ethanol (2.0 mL) solution and boiling of it for 1 min yielded a dark brown solution.The solution was left at room temperature (22 °C) undisturbed for 1 month, upon which time dark brown crystals were formed suitable for single-crystal X-ray diffraction analysis.The crystals were filtered and dried under vacuum.).NaV V O 3 (0.0024 g, 0.020 mmol) was dissolved in distilled water (1.000 mL), and solid H 4 qtn (0.0046 g, 0.01 mmol) was added to it.The mixture was heated to 100 °C, the ligand was dissolved, and the solution's color became yellow.The solution was left to reach room temperature, and then solid PPh 4 Cl (0.0075 g, 0.02 mmol) was added to it.The mixture was heated to boil until all solids were dissolved.The solution was cooled down to room temperature, and 0.0071 g of yellow crystals suitable for single-crystal X-ray diffraction analysis were formed.Yield: 55% (based on H The synthesis of the ligands is depicted in Scheme 3 and is based on the nucleophilic substitution of cyanuric chloride and takes place in two steps.The first step involves the reaction of the bridging group (either 1,4-hydroquinone or 1,4-phenyldiamine or ethylenediamine) with cyanuric chloride at 0 °C and in the presence of DIPEA to afford qtCl 4 , pdCl 4 , and enCl 4 .Temperature should be kept strictly at 0 °C to avoid further substitution of the triazine.The second step involves the substitution of the remaining four chlorine atoms by reacting qtCl 4 , pdCl 4 , and enCl 4 with an excess of N-methylhydroxylamine at basic solutions.The organic ligands (H 4 qtn, H 4 pdl, and H 4 enl) are insoluble in aqueous solution in a wide range of pHs 3−10 (Figure S1).It is worth mentioning here that the right choice of the solvents for the synthesis of the ligands is very important in order to obtain pure products and high reaction yields.
reacted with the BLs in aqueous or alcoholic solutions.When [U VI O 2 (NO 3 ) 2 (H 2 O) 2 ]•4H 2 O was used as a starting material, KOH was added to the solution with a molar ratio of [U VI O 2 ] 2+ :H 4 qtn:KOH 2:1:4.The synthesis of the binuclear vanadium(V) complexes 2, 4, and 6 was accomplished by reacting an aqueous solution of NaV V O 3 with BLs (V V O 2 + :BL 2:1) (Scheme 4).After the end of the reaction, PPh 4 Cl was added to the solution resulting in the precipitation of complexes 2, 4, and 6.The U VI and V V binuclear complexes are soluble in water at pH ≥ 7.At pH < 7 the dissolved complexes precipitate out.Thus, all solution studies were performed at pHs 7, 9, 10, and 11.For practical reasons, the stability investigations were conducted at pH 9 or 10 to allow the BLs to dissolve in water.

Inorganic Chemistry
The findings demonstrate that production of the [U VI O 2 2+ − OH] species at high pHs (>8.5) is the only distinction between pHs 7 and 9.The stability of the complexes increases as the pH decreases, but the reactivity is unchanged at either pH.Therefore, the information from this study done at pH 9 or 10 can be extrapolated to pH 7.
Compounds 7−13 were synthesized in solution and characterized by 1 H NMR and MS.The heteroleptic complexes 7−10 were synthesized by adding 2 equivalents of either H 2 bihyat (7) or H 2 dipic (8−10) to 1 equivalent of aqueous solutions of the complexes 1, 3, or 5 (Scheme 4).The heterometallic compounds 11−13 formed in solution after the addition of V V O 4 3− in the aqueous solution of 1, 3, or 5 or [U VI O 2 ] 2+ in the aqueous solution of 2, 4, or 6.Both homometallic and bimetallic complexes are present in the solution after the reaction (Scheme 4).
Characterization of the Complexes.X-ray Crystallographic Results.A summary of the crystallographic data and the final refinement details for binuclear complexes 1−4 and 6 are given in Tables S1 and S2.Interatomic distances and bond angles relevant to the U VI and V V coordination spheres are listed in Tables S3 and S4.ORTEP plots of the crystal structures of the binuclear complexes 1, 3 and 2, 4, 6 are shown in Figures 1 and 2  This is the second crystallographically characterized example of an uranium complex incorporating a triazine ligand, which also shows the bonds between the U VI ion and triazine nitrogen atom (∼2.43 Å) are much stronger than the bonds between [U VI O 2 ] 2+ and other related pyridine type nitrogen atoms (2.52−2.64Å). 43 For example, [U VI O 2 (dipic)(H 2 O) 2 ] has a U VI −N py bond length of 2.520(6) Å. 44 The strong U VI −N tr bond is attributed to the resonance structure B (Scheme 5) of the BLs.The flat sp 2 -hybridized hydroxylamine nitrogen atoms reveal that conformation B contributes mainly to the structure of the complex.In conformation B, the hydroxylamine nitrogen atoms are approximately sp 2 hybridized, and thus the ring nitrogen atoms possess high electron densities.Therefore, a 2+ and [V V O 2 ] + complexes. 13,14he UV−vis spectra of the aqueous solutions of the binuclear complexes 1−6 at various pHs are shown in Figures S5−S7.The UV−vis spectra of the aqueous solutions of the uranyl complexes 1, 3, and 5 at pHs 7.0−10.0exhibit a broad signal covering a region from 300 to 700 nm consistent with the brown color of the solutions assigned to LMCT.The respective spectra of the aqueous solutions of the vanadate complexes 2, 4, and 6 also gave a broad band at higher energy ranging from 300 to 500 nm consistent with the light-yellow color of the solutions.The spectra of the binary binuclear complexes  1.The spectra of the uranyl complexes 1, 3, and 5 at pD = 7.0 exhibit peaks at 3.489 and 7.264 ppm for 1, at 3.574, 3.596, and 7.552 ppm for 3, and at 3.568, 3.574, and 3.605 for 5, assigned to the hydroxylamine methyl [H(1), H(1′)] and the [H(4)] protons of the bridging ligand, respectively.The peaks are shifted to lower field vs the respective peaks of the free BLs, confirming ligation of the BLs to the [U VI O 2 ] 2+ moiety.At pDs > 7, new broad peaks appeared in the 1 H NMR spectra of the D 2 O solutions of 1, 3, and 5 assigned to 2+qtn 4− species and confirmed by electrospray ionization mass spectrometry (ESI-MS) (vide infra). 13,46This is in agreement   13 The presence of more than one species in solution at pHs > 7 agrees with the UV−vis spectra, which are different at various pHs (vide supra) and are detected by MS (vide infra).In addition, the formation of the charged species 2+ -qtn 4− is supported by the high increase of the solubility in H 2 O similar to that of the neutral The 1 H NMR spectra of the D 2 O solutions of the vanadate complexes 2, 4, and 6 at pDs = 7.0−11.0exhibit peaks at 3.280 and 7.232 ppm for 2, at 3.371 and 7.546 ppm for 4, and at 3.178, 3.137, and 3.486 for 6, assigned to the hydroxylamine methyl [H(1), H(1′)] and the [H(4)] protons of the bridging ligand, respectively.
The peaks are shifted at lower field vs the respective peaks of the free BLs due to ligation of the BLs to [V V O 2 ] + structural unit; however, the shift of the peaks of aliphatic protons is 0.2 ppm less than the respective uranyl complexes.The presence of only one symmetric species in solution at various pHs (Figure S11) agrees with the UV−vis spectra.
At this point, it is worth noting that the hydroxylamine methyl groups [H 1 , 1d ′ (C 1,1d ′ )] of BLs and BLs' complexes are chemically nonequivalent.However, all compounds except 5 and 6 in the 1 H NMR spectra give only one signal for both H(1)and H(1′).This is attributed to the fast exchange between the hydroxylamine methyl groups through either rotation of the triazine ring around the C(5)−X bond (X = N or O), when BL is in resonance form A [Scheme S1A(a)], or flip of the triazine ring around atom X when BL is in resonance form B [Scheme S1A(b)].The 2D EXSY and VT 1 H NMR spectroscopies 18 (Figures S13 and S14) reveal an exchange mechanism similar to the inverse umbrella of amines.In the case of the 1,4phenylenediamine and ethylenediamine complexes 3−6, the exchange mechanism proceeds first through the deprotonation of N(6)−H (Scheme S1C).The N(6)−H proton is more acidic for the 1,4-phenylenediamine than the ethylenediamine complexes, resulting in a faster exchange reaction rate for the former.The fluxional behavior of the complexes is further discussed in the ESI (Scheme S1).
The 51 V NMR spectra of the vanadate complexes in solution (D 2 O) at pDs 5.0−11.0(Figure S12) exhibit only one broad peak at −513 ppm, and this fact reveals that the complexes are hydrolytically stable.At pD 11.3, a very small quantity of V V O 4 3− (∼5%) is formed.In contrast to uranyl-BL complexes which are hydrolytically stable up to pH 12, the respective vanadate compounds are hydrolyzed above pH 11.The 51 V NMR chemical shifts of the peaks of 2, 4, and 6 are close to the peak of [V V O 2 (bihyat)] − (−502 ppm), confirming the formation of the complex with the triazine-hydroxylamino chelate moiety.
Thermodynamic Stability of Complexes 1−6.Determination of the Stability Constants of V V O 4 3− with BLs at pH = 9.0 by UV−Vis and 1 H NMR Spectroscopies.The solution studies with BLs were not an easy task mainly due to the insolubility of the ligands (Figure S1) and thus were dissolved at high pHs above 12 in their stock solutions.Aliquots of these solutions were used in the NMR and UV−vis experiments at pHs 7−10 and concentrations ∼1 mM.The free ligand in these experiments remained soluble for approximately 24 h.
Stepwise addition of V V O 4 3− into the solutions of BLs was monitored by 1 H NMR spectroscopy and shows the formation of two species, the mononuclear [V V O 2 (H 2 BL)] − and the binuclear [(V V O 2 ) 2 (μ-BL)] 2− .The mononuclear species are asymmetric and give two sets of peaks for the free and the ligated triazines.For example, H 2 qtn 2− and H 2 pdl 2− in [V V O 2 (H 2 BL)] − shift two aromatic peaks [H(4)] ∼ 0.04 ppm to lower field from the free ligand and ∼0.04 ppm to higher field than the ligand in [(V V O 2 ) 2 (μ-BL)] 2− .The stability constants (K 2qtn = 0.30 ± 0.02, K 2pdl = 0.30 ± 0.01, and K 2enl = 0.23 ± 0.01, eq 1) of the equilibrium shown in eq 2 were calculated from the 1 H NMR spectra of solutions of V V O 4 3− and BLs at various concentrations (Figures S15 and S16).The values of K 2BL show that the BLs with aromatic bridges stabilize more the binuclear vs mononuclear complexes than the BL with the aliphatic bridge, attributed to the interactions through the bridge between the two metal ions in qtn 4− and pdl 4− ligands.
Apparently [U VI O 2 ] 2+ forms both mononuclear and binuclear species; however, the peaks were too broad due to the formation of uranyl−OH species, and it was not possible to be separated by NMR.The 1 H NMR measurements show that for both metal ions at concentrations >0.1 mM (BL) and at ratios 2:1 (metal ion:BL) and at the pD range 7−10, the binuclear species exist only in solution.
The only difference between UV−vis spectra of the aqueous solutions of vanadium complexes and the respective spectra of the ligands is a shoulder at 380−480 nm due to LMCT electron transitions.SQUAD 47 was fed with the data of spectra of solutions containing various concentrations of vanadate (0.5− 2.2 mM) and BL (0.8−1.2 mM) for each BL.The results were satisfactory only for pdl 4− −VO 4 3− giving the best fit for β 11pdl = 8.9 and β 21pdl = 17.0.The standard deviation in absorbance data for enl 4− and qtn 4− was more than 1% mainly due to the error from the poor quality of the absorbance data since the LMCT peak was very close to the absorbance of the ligand.The K 2pdl (eq 1) calculated from the UV−vis data was smaller (0.18) in comparison to the value with NMR, attributed to the presence of the buffer (Tris) in the solution, which is known to form complexes with vanadate. .H 2 dipic has been chosen because it is the strongest aminocarboxylate ligand for uranyl, 49 while the ligand H 2 bihyat has exceptional strength for both metal ions, surpassing even amidoximes and aminocarboxylate ligands. 13he CO 3 2− is a potent uranium ligand and the primary marine uranyl species ].

Inorganic Chemistry
The Considering that the concentration of H 2 O is constant, it can be included in K dipic(BL) , and thus K dipic(BL) can be calculated from The chemical shifts of protons H(1) of complex The aromatic protons of the free H 2 dipic give peaks at 7.823 ppm (pD = 10.0), 7.886 ppm (pD 9.0), and 7.925 ppm (pD 7.0).The dipic 2− ligated to [U VI O 2 ] 2+ gives peaks at 8.421, 8.373, and 8.347 ppm for complexes 8, 9, and 10, respectively, at pDs 7−11.The larger the deshielding of the peaks of dipic 2− ligated to the metal, the stronger the coordination of [U VI O 2 ] 2+ with dipic 2− .This suggests that the BL electron-donating strength is qtn 4− < pdl 4− < enl 4d − with qtn 4− being the weaker electron donor of all BLs.The stronger binding of dipic 2− in 8 than 9 and 10 is depicted and from the 1 H NMR calculated equilibrium constants The slow rate of [V V O 2 ] + reaction with 1, 3, and 5 might be attributed to a mechanism in which the U VI -μ-OH-U VI bonds break down toward the formation of U VIμ-O-V V oxometallates, and then [V V O 2 ] + replaces the U VI −O−V V moieties.The suggested mechanism is also supported from the fast rates of substitution of [U VI O 2 ] 2+ from [V V O 2 ] + in 1, 3, and 5 at lower pDs (7.0), whereas the formation of U VI −O-V V cluster is less likely.In addition, the fast rates of the reverse reactions of 2, 4, and 6 with [U VI O 2 ] 2+ to give 1, 3, 5, and 11−13 are also evident for the mechanism because 2 does not form V Vμ-O-V V -qtn 4− molecules, and therefore, the coordination of [U VI O 2 ] 2+ is not inhibited.
The  .In addition, 11 gave two doublets for the hydroquinone protons (7.310, 7.256 ppm and J 4−5 = 7.6 Hz, Figure 5), and 12 gave two broad peaks at 7.468 and 7.408 ppm.2D 18 grCOSY has been used to identify the coupling between the aromatic protons (Figure S28).The 1 H NMR spectra of complex 13 gave two peaks at 3.083 and 3.043 assigned to the methyl groups of hydroxylamines.
After the addition of V V O 3 − into the solutions of 1, 3, or 5, a yellow precipitate was formed.The 51 V NMR spectra of the solutions did not show any signal attributable to the V V O 4 3− anion even with an excess of vanadate in solution, indicating that U IV O 2 2+ coprecipitates with V V O 4 3− as a 1:1 salt.At this point, it is worth noting that when excess of V V O 4 3− is added in the aqueous solution, U VI O 2 2+ -bihyat results in the formation of the heterobimetallic   3) and (c) for H 4 enl: 83% (6): 17% (13): 0% (5).The ligands become better binders for uranyl at pDs > 10.The results show that BLs are stronger vanadium binders than uranium in agreement with the theoretical calculations.H 4 enl is the stronger vanadium binder, whereas H 4 pdl shows preference for uranyl at pHs > 10.
The decrease of the selectivity of BLs vs bihyat 2− to bind [U VI O 2 ] 2+ might be attributed to the difficulty, defined by the binuclear geometry of U−BL complexes, to acquire [U VI O 2 (BHT) 2 ] 2− -type coordination in solution.However, as shown in this study, the equilibrium between either the binucleating or mononucleating ligands in solutions containing both V V O 4 3− and [U VI O 2 ] 2+ is very complex.This has to do with the generation of various bimetallic V 2+ inorganic species that might be also responsible for the selectivity.
The mononucleating ligand H 2 bihyat at alkaline pDs >7 forms [U VI O 2 (bihyat) 2 ] 2− , significantly increasing the affinity and selectivity of the ligand toward [U VI O 2 ] 2+ .In addition, the larger negative charge of offer an extra stabilization for the binuclear vanadate complexes, through a better solvation, than the neutral The results of the 1 H NMR stability studies are summarized in Scheme 6.
ESI-MS.The ESI-MS studies of the solutions of BLs with uranyl or vanadate at pH = 9.0 are shown in Figure S45.The MS spectra show peaks assigned mainly to the bimetallic species.The MS spectra of the uranyl show the presence of a larger number of species including clusters of higher molecular weight than the vanadate−BL solutions.
ESI-MS provided a unique opportunity in this work not only to identify 52−57 and confirm the structural stability of the species in the reaction mixture as a function of the pH value but also allowed us to monitor the occurred speciation and selectivity of the designed ligands against the heavy metals under investigation.−57 Additionally, it allowed us to sharpen the data obtained from the NMR studies discussed above and draw safer conclusions following this cooperative study.Initially we investigated the behavior of the reaction mixture using either H 4 qtn or H 4 enl in the presence of a single transition metal (either [U VI O 2 ] 2+ or [V V O 2 ] + ) under identical experimental conditions.Figure S45 demonstrates the ability of both ligands to coordinate with the transition metals of interest forming bimetallic species.In the case of H The second part of our study involved the investigation of the competitive nature of ligands for [U VI O 2 ] 2+ metal centers based on their known coordination abilities (Figure S46).More specifically, we explored the mixtures of H 4 qtn/H 2 bihyat, H 4 pdl/H 2 bihyat, H 4 qtn/H 2 dipic, and H 4 enl/H 2 dipic all in 1:2 ratios in the presence of 2 equiv of [U VI O 2 ] 2+ .In every case, the ditopic ligands H 4 qtn, H 4 pdl, and H 4 enl exhibited their efficacy for coordination by "capturing" in every case two [U VI O 2 ] 2+ centers.In a competitive chemical environment of H 4 qtn and H 2 bihyat, the majority of the species appear to be bimetallic and monometallic complexes of H 4 qtn with their distribution envelopes centered at 715.1, 779.2, and 828.3 m/z and to a lesser extent H 4 qtn:H 2 bihyat 1:1 moiety (644.1 m/z).Interestingly, in the case of H 4 pdl/H 2 bihyat couple, only monometallic [U VI O 2 ] 2+ species of H 4 pdl have been identified with the relevant singly charged distribution envelope centered at 713.1 m/z.Moving on to the last two cases of H 4 qtn/H 2 dipic and H 4 enl/H 2 dipic, the increased coordination ability of H 2 dipic becomes apparent.In both cases, we were able to identify bimetallic [U VI O 2 ] 2+ species of 1:1 as well as 1:2 ratios of H 4 qtn/H 2 dipic and H 4 enl/H 2 dipic ratios with the relevant doubly charged distribution envelopes centered at 658.1, 677.0, and 695.0 m/z and 633.1, 638.9, 651.5, and 670.9 m/z values for the two cases of mixed ligand systems, respectively.
Finally, we embarked on an effort to explore the behavior of the ditopic ligands in the competitive coordination environment of [U VI O 2 ] 2+ and [V V O 2 ] + .In the case of the more rigid ligand H 4 qtn, we observed a range of doubly charged bimetallic

■ COMPUTATIONAL RESULTS
To assess the complexation stability of the four ligands (bihyat 2− , qtn 4− , enl 4− , and pdl 4− ) to uranyl and vanadate, a computational survey concerning the complexation reactions of all ligands was carried out (see Computational Methods section).Geometry optimizations were performed on the obtained crystal structure coordinates, and in their absence, the atoms were edited to obtain the respective isomer.
The main challenge is to find a suitable reference state reactant in aqueous solution.The problem is further compounded by the pH dependence of the process.Since the pH values of the reactions are close to the neutral range, both acidic and alkaline reactions will be considered.
From the literature data, namely, Cruywagen's review, 58 it is reasonable to assume that at high concentrations of H + , the dominant species of vanadium(V) will be [V V O 2 ] + , whereas in alkaline solution, it will be dihydrogen vanadate H 2 V V O 4 − .For the case of uranyl, there is a speciation study by Panias and Krestou 59 that establishes the predominance of [U VI O 2 ] 2+ in acidic conditions and [U VI O 2 (OH) 3 ] − in basic media.
The following complexation free energies of a set of test reactions were computed: where L = qtn 4− , enl 4− , and pdl 4− .These will be representative of a proton rich medium.For the bihyat 2d − ligand, the simpler monometallic complexation will take place with three water molecules leaving.These results are summarized in Figure 6 below.
It should be noted that the overall absolute values in Figure 6 are likely to be inflated since the bihyat 2− , qtn 4− , enl 4− , and pdl 4− ligands will likely be partially protonated in solution.
These numbers, however, allow us to draw some interesting trends.Throughout the spectrum of ligands, there is a consistent preference for the complexation with vanadate.The mixed The qtn 4− ligand stands out as having the most affinity for the metal oxido units.
In order to assess the alkaline solution regime, the next series of complexation free energies were computed in accordance with the reaction schemes: For the uranyl species, since the hydroxide anion is a poor leaving group, reaction 3 will be endergonic.It was decided therefore to weigh this reaction against the autoionization of water so that the more stable water molecule could be the leaving group.
The same was carried out for vanadate with a slightly different variation, i.e., and for the mixed species For the bihyat 2− ligand, the following monometallic reactions were tested: The figures of these reactions are depicted in Figure 7.It may be seen that the anionic oxido species afford a different stability scenario.
Within each class of ligand, the complexation energies of dihydrogen vanadate and trihydroxouranyl are much closer, almost to the point of indistinguishability.In the case of enl 4− ,for example, the complexation energies are exactly the same, i.e., −66.7 kcal mol −1 .The most contrasting values in the bimetallic class are with the qtn 4− ligand where the homometallic dimers are 4 kcal mol −1 apart.In the case of bihyat 2− , the difference is 5.5 kcal mol −1 between H 2 V V O 4 − and [U VI O 2 (OH 3 )] − .The calculations reveal that the V V -bihyat 2− complex is more stable than U VI -bihyat 2− in contrast to the experimental results. 13owever, in the theoretical studies, the presence of the U VI species with two bihyat 2− {[U VI O 2 (bihyat) 2 ] 2− } and the −OH bridged binuclear U VI -bihyat 2− have not been considered.Nevertheless, the theoretical studies show that the ligation of the mononucleating ligand with V V or U VI is much weaker than BLs, in agreement with the experiment.
A two-fragment molecular orbital (FMO) analysis was also performed on the {[U VI O 2 (H 2 O) 2 ] 2 BL} species in order to quantify the electron donation from the anionic ligands to the metal sites.The two fragments were the two [U VI O 2 (H 2 O) 2 ] 2+ moieties plus the BL 4− ligands qtn 4− , pdl 4d − , and enl 4− .The FMO Mulliken populations are −0.277,−0.300, and −0.315, the minus sign signifying that the electron transfer goes from the ligand fragment BL 4− to the two-site cationic fragment.This is  consistent with the NMR results which demonstrated the 1 H chemical shift changing in the same direction (Figure S39).

■ CONCLUSIONS
The binuclear complexes [(U VI O 2 ) 2 (BL)(H 2 O) 4 ] and [(V V O 2 ) 2 (BL)] 2− with the novel hydroxylamino-triazine binucleating ligands H 4 qtn, H 4 pdl, and H 4 enl (BLs) were synthesized and structurally and physicochemically characterized.The X-ray structure analysis of both metal ions with BLs reveals an extraordinary strong binding of BLs to [U VI O 2 ] 2+ and [V V O 2 ] + .The ligand BLs used in this study are much stronger chelators than the amidoximes that are currently utilized for uranyl mining from the sea, according to competing investigations of the BLs with ligands like H 2 dipic and H 2 bihyat.This is attributed to the negative formal charge of the triazine nitrogen atom and the deprotonated hydroxylamine oxygen donor atoms.The UV−vis and 1 H and 51 V NMR spectra of the aqueous solutions of binuclear complexes 1−6 confirm the strong binding properties of BLs to [U VI O 2 ] 2+ and [V V O 2 ] + and also reveal the high thermodynamic stability of the complexes in a large pD range, 7−12.The bridging moiety of the ligands influences the stability of the complexes, with the ligands exhibiting aromatic bridges, qtn 4− and pdl 4− , to form less stable complexes than the aliphatic, enl 4− .This is attributed to the better delocalization of the negative triazine charge in the aromatic rings than the aliphatic chain and, thus, lower basicity for the chelating moieties.ESI-MS and 1 H NMR have shown that uranyl complexes in solution at alkaline pH form U VI −OH− U VI polymeric species.
Reactions of either H 2 dipic or H 2 bihyat with the uranyl complexes 1, 3, and 5 result in the formation of heteroleptic binuclear complexes 7−10 as evident from 1 H NMR spectroscopy and ESI-MS.In the equatorial plane of the binuclear complex 7, the ligands qtn 4− -bihyat 2− and in complexes 8−10, the ligands BLs-dipic 2− coexist.Complexes 3 and 5 do not react with H 2 bihyat to form the heteroleptic binuclear uranyl complexes, and this is attributed to the strong electron donor properties of pdl 4− /enl 4− that do not allow the coordination of a strong donating ligand (bihyat 2− ) in a trans position.This finding suggests that two triazine-hydroxylaminate chelate groups from the two strong donating BLs cannot occupy the equatorial plane of [U VI O 2 2+ , supporting the possibility that this type of chelation is the basis for bihyat 2− 's preference for [U VI O 2 ] 2+ over [V V O 2 ] + .The calculated net interfragment electron donations of the BLs to [U VI O 2 ] 2+ is linearly dependent on the 1 H NMR chemical shift of the protons of dipic 2− lying at the equatorial plane of complexes 8−10, supporting that qtn 4− is a weaker electron donor than pdl 4− / enl 4− .High excess up to saturation in water of either H 2 dipic or H 2 bihyat or CO 3 2− does not replace BLs − from complexes 1−6.Considering that H 2 bihyat is one of the strongest ligands for [U VI O 2 ] 2+ and [V V O 2 ] + , the BLs form uranium(VI) and vanadium(V) complexes that are even more thermodynamically stable than H 2 bihyat, which was also confirmed by theory.Reactions of uranyl with the vanadate complexes 2, 4, and 6 result in the formation of the homometallic 1−6 and heterometallic 11−13 binuclear complexes as evident from 1 H NMR spectroscopy and ESI-MS.The reverse reaction, i.e., addition of vanadate to uranyl complexes 1, 3, and 5, is a much slower reaction than the addition of uranyl to vanadate complexes because of the formation of the U VI −OH−U VI −BL polymeric species.Although the thermodynamic stability of [U VI O 2 ] 2+ /BLs and [V V O 2 ] + /BLs − has increased significantly compared to bihyat 2− , the BLs are less selective for [U VI O 2 ] 2+ over [V V O 2 ] + than bihyat 2 since the most stable complexes in solution are [(V V O 2 ) 2 (μ-BL)] 2− .From the three binucleating ligands, enl 4− forms the most stable hydrolytically metal complexes as predicted from the theoretical calculations.
In conclusion, the binucleating BHT-type siderophores, such as BLs used in this study, exhibit exceptional thermodynamic stability for hard metal ions; thus, they are potentially suitable for biodetoxification and hard metal separation technologies.In order to increase selectivity for [U VI O 2 ] 2+ over [V V O 2 ] + , new chelators have to be designed forcing the coordination of two triazine chelating groups at the equatorial plane of the metal ion.However, as depicted in this work, the electron-donating properties of the two chelators at the equatorial plane of [U VI O 2 ] 2+ should be judiciously chosen, thus minimizing the competition between the groups to ligate uranyl.

Scheme 4 . 13 Figure 1 .
Scheme 4. Synthesis of the Binuclear Complexes 1−6 of the Heteroleptic Uranium(VI) Complexes 7−10 and of the Heterometallic (U VI /V V ) Complexes 11−13 1 and 6 are similar to the UV−vis spectra of the aqueous solutions of [U VI O 2 (bihyat)-(H 2 O) 2 ] and [V V O 2 (bihyat)] − , respectively.The UV−vis spectra of the aqueous solution of vanadate complexes are the same at pHs 7.0−10.0,revealing that in this pH range, the complexes retain their integrity.On the other hand, the UV−vis spectra of the aqueous solution of the uranyl complexes 1 show that the speciation is altered by increasing the pH from 7.0 to 9.0 (Figures S5−S7).NMR Spectroscopy.The 1 H NMR of complexes 1−6 and the 51 V NMR spectra of 2, 4, and 6 in solution (D 2 O) at various pDs are shown in Figures S8−S12.The NMR data are summarized in Table

2 4+-
7 (3.516ppm) are deshielded after the replacement of the two water molecules of 1 [H(1)3.486ppm] by bihyat 2− .The 1 H NMR peaks of the bound ligand to U VI -bihyat 2− [H(5) 3.583 ppm and H(6,7) 3.721 ppm] are shifted to lower field toward the peaks of free H 2 bihyat [H(5)3.248ppm and H(6,7) 3.659 ppm; (Figure S19)] at both pHs 7.0 and 9.0.The H(4) protons of the binuclear complexes 8 [7.336 ppm] and 9 [7.527] are shifted downfield compared with the complexes 1 [7.318 ppm] and 3 [7.321ppm].The aliphatic protons H(1,1′) for complexes 8−10 and H(4) for 10 give well-defined peaks compared with the broad signals of 1, 3, and 5 due to the formation of U VI O 2 -(μ-OH) 2 -U VI O 2 4+ -BL 4− species and shifted to lower field.It is worth mentioning that the broad peaks of the 1 H NMR spectra of the uranyl−BL complexes at pDs > 7 after the addition of dipic 2− become sharp.This is because the coordination of dipic 2− to the uranyl−BL complexes blocks the sites available for the formation of U VI O 2 -(μ-OH) 2 -U VI O BL 4− species.Apparently, such species do not form in solution, and the only species are complexes 8, 9, or 10 depending on the BL ligand.

1 H
NMR spectra of the mixed-metal asymmetric complexes 11 and 12 in D 2 O show two peaks for the CH 3 − N−O − moieties at 3.497, 3.255, and 3.584, 3.221 ppm, respectively (Figures S35−S38 )

Figure 5 .
Figure 5. Aliphatic part of the 1 H NMR spectra of 1 in solution (D 2 O) and V V O 4 3− (20 mM) at pD = 9.0 vs time showing the slow formation of 2 and 11.The signals denoted with the asterisk originated from the H 1 peaks of U VI O 2 -(μ-OH) 2 -U VI O 2 4+ -qtn 4− species.

Scheme 6 .
Scheme 6. Summary of the Thermodynamic Stability of the V V and U VI Complexes on the Basis of 1 H NMR Spectroscopy, (A) V V O 4 3− -BLs Titration, (B) Competition Studies of BLs and H 2 dipic for [U VI O 2 ] 2+ Binding.(C) [V V O 2 ] + Binding in the Presence of two BLs.(D) Binding Selectivity of BLs toward V V O 4 3− and [U VI O 2 ] 2+ ; the % is the Percentage of the Three Complexes Formed in Solution 4 qtn and [U VI O 2 ] 2+ , we observed doubly charged characteristic isotopic envelopes located in the region of 1000−1100 m/z values which c a n b e a s s i g n e d t o t w o b i m e t a l l i c m o i e t i e s {(U V 2 O 10 N 10 C 16 H 16 ) 2 (H 2 O) 5 } 2− located at 1029.1 m/z flanked by a series of envelopes attributed to the same moiety with varying combinations of solvent molecules.In the case of [V V O 2 ] + , we observed again a vanadium-based bimetallic species with a relevant distribution envelope centered at 949.0 m/z and can be assigned to {(V V 2 O 10 N 10 C 16 H 16 )(Ph 4 P)} − .Interestingly in the case of H 4 enl and [U VI O 2 ] 2+ and due to the flexibility of the ligand, we observed doubly charged bimetallic species in the region of 450−600 m/z but also a tetrametallic triply charged [U VI O 2 ] 2+ species located at 657.1 m/z with a formula of {(U 2 O 8 N 12 C 12 H 18 ) 2 (CH 3 OH)(OH 2 ) 3 OH} 3− .

48 [U VI O 2 ] 2+ /[V V O 2 ] + , BLs Binding in the Presence of either H 2 dipic or H 2 bihyat or CO 3 2− Monitored by 1 H NMR Spectroscopy.
The stability of the vanadium and uranium−BL complexes was evaluated in the presence of either H 2 dipic or H 2 bihyat and CO 3 with their relevant envelopes centered at 304.0, 609.0, and 515.1 m/z values with formulas {(V I V 2 O 8 N 1 2 C 1 6 H 1 8 )} 2 − , {(V I V 2 O 8 N 1 2 C 1 6 H 1 8 )H} − {(U VI U V O 9 N 12 C 16 H 18 )(CH 3 OH)} 2− , as well as mixed-metal bimetallic [U VI O 2 ] 2+ /[V V O 2 ] + ,with their distribution envelopes centered at 406.0 and 795.1 m/z attributed to {(U VI V IV O 8 N 12 C 16 H 18 )OH} 2− and {(U VI V IV O 8 N 12 C 16 H 18 )} − , respectively, as shown in Figure S47A.Interestingly, in the case of the more flexible ditopic H 4 enl ligand, there was a preference toward the formation of singly charged bimetallic [V V O 2 ] + species centered at 561.0, 582.9, and 598.9 m/z attributed to {(V V 2 O 8 N 12 C 12 H 18 )H} − , {(V III 2 O 8 N 12 C 12 H 18 )H 5 (H 2 O)} − , and {(V IV V V O 8 N 12 C 12 H 18 )H 3 (H 2 O) 2 } − , respectively, even though a small trace of also singly charged [U VI O 2 ] 2+ / [ V V O 2 ] + m i x e d -m e t a l b i m e t a l l i c m o i e t y {(U V V V O 8 N 12 C 12 H 18 )} − has been detected at 747.1 m/z.

■ ASSOCIATED CONTENT * sı Supporting Information The
Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.inorgchem.3c02678.Electronic Supporting Information (ESI) available: For ESI and crystallographic data in CIF for other electronic format see DOI: Solubility of H 4 qtn vs pH; IR spectra; variable pH UV spectra; 1 H NMR spectra; VT 1 H NMR spectra; calculation of K 2pdl from 1 H NMR; speciation diagram based on the spectroscopic titration of 1.000 mM H 4 pdl and addition of various quantities of [VO 4 3− ] at pH 9.1; aromatic and aliphatic parts of the 1 H NMR spectra; ESI-MS spectra; crystal data and structure refinement for compounds 1, 2, 3, 4, and 6; interatomic distances (Å) and angles (deg) relevant to the U VI and V V coordination sphere; and DFT-optimized structures CCDC: 2211326 for 1, 2211327 for 2, 2284962 for 3, 2284963 for 4 and 2284964 for 6 A data set collection 60 of the optimized structures is available in the ioChem-BD repository 61 (PDF) CCDC 2211326−2211327 and 2284962−2284964 contain the supplementary crystallographic data for this paper.These data can be obtained free of charge via www.ccdc.cam.ac.uk/ data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.