Discrete Ti−O−Ti Complexes: Visible‐Light‐Activated, Homogeneous Alternative to TiO2 Photosensitisers

Abstract A series of novel bimetallic TiIV amine bis(phenolate) complexes was synthesised and fully characterised. X‐ray crystallography studies revealed distorted octahedral geometries around the Ti centres with single or double oxo‐bridges connecting the two metals. These robust, air‐ and moisture‐stable complexes were employed as photosensitisers generating singlet oxygen following irradiation with visible light (420 nm) LED module in a commercial flow reactor. All five complexes showed high activity in the photo‐oxygenation of α‐terpinene and achieved complete conversion to ascaridole in four hours at ambient temperature. The excellent selectivity of these photosensitisers towards ascaridole (vs. transformation to p‐cymene) was demonstrated with control experiments using a traditional TiO2 catalyst. Further comparative studies employing the free pro‐ligands as well as a monometallic analogue highlighted the importance of the ‘TiO2‐like’ moiety in the polymetallic catalysts. Computational studies were used to determine the nature of the ligand to metal charge transfer (LMCT) states and singlet–triplet gaps for each complex, the calculated trends in the UV‐vis absorption spectra across the series agreed well with the experimental results.


Introduction
Photocatalytic transformations are increasingly attractive as they offer environmentally friendly pathways for ar ange of chemicalprocesses including water purification,water splitting, CO 2 conversion and organic syntheses. [1][2][3][4] The rapid rise of flow photoreactors, coupled with affordable LED light-sources in the past decadeh as furtherp romoted the development of both heterogeneous and homogeneous photocatalytic systems. [5] Catalystst hat display as trong response to visible light (400-700nm) are desirable, as they are safer to use and enable the efficient utilisation of naturals unlight whilst preventing potentials ide-reactions andc atalystd egradationt hat commonly occur under high energy UV irradiation (< 400 nm). [2,6] Various forms of the ubiquitous titania (TiO 2 )c atalystsh ave been successfully appliedi nc lassical UV-activated photochemistry due to their abundance,l ow toxicitya nd large band gap energy. [7] To extend the absorption into the visible region, however, TiO 2 needs to be doped with additives including metals (Cd, Ce, Mn, Bi etc.) and non-metallic anions. [8][9][10] While the incorporation of these (often expensiveo rt oxic) components significantly increases the photocatalytic efficiency,i tc an simultaneously lower the thermals tability of the catalyst and create undesired electron traps. [10] Other TiO 2 -like materials, such as polyoxotitanates (POTs) have also been investigated as photocatalysts. [11] Modifications of POTs for enhanced visible light harvesting include heterometallic doping or the incorporation of simple functional ligands that influence the absorption. [12] While heterogeneous systemsu sually benefit from higher stabilitya nd easier separation, the application of homogene-ous photocatalysts often allows betterf ine-tuning that leads to enhanced activity and selectivity, [13] moreover they enable convenient,s olution-phase reactionm onitoring and mechanistic studies. In the past decades av arietyo fw ell-defined, soluble molecular catalysts have been designedf or photochemical processes comprising photo-organocatalysts (including organic dyes) and metal complexes. [14][15][16] The latter group is dominated by polypyridyl complexes of Ru and Ir for photoredox reactions, [17][18][19] while transition metal complexes of porphyrin and phthalocyanine-derivatives have been frequently applied as photosensitisers. [20][21] An important photocatalytic reaction is the generation of singlet oxygen ( 1 O 2 ), which can be employeda sagreen oxidising agent in dye degradation, wastewater disinfection, cancer treatment and synthetic processes. [22][23][24] This techniquer equires ap hotosensitisert hat can exist in ar elatively long-lived triplet excited state, by efficientlyu ndergoing inter-system crossing following absorption of ap hoton of the appropriate wavelength. [25][26] The energy is consequently transferred onto ground-state triplet oxygen molecules ( 3 O 2 )c onverting them into metastable 1 O 2 . [27][28][29] Most commonly,o rganic dyes such as methylene blue have been applied as photosensitisers. [30][31] More recently,c omplexes of preciousm etals (Ru, Re, Os, Ir and Pt) have also been used, often as bimodal catalysts with large, light-harvesting moieties incorporated into the ligand framework. [32][33][34][35][36][37] Despite the popularity of TiO 2 and POT-based systems, the utilisation of discrete,w ell-defined complexes of Ti is underexplored in the field of photocatalysis. [38][39][40] Our group has had a longstanding interest in the application of this abundant and non-toxic metal, particularly in combination with amine bis(phenolate) (ABP) ligandsd ue to their convenient synthesis and easily tailored stereoelectronic properties. [41][42] The employmento fT iA BP complexesi np hotocatalysis is promising, as they combine the benefits of TiO 2 -like motifs (via TiÀOa nd TiÀOÀTi moieties) with the benefit of adjusting their light absorptioni nto the visible region (as indicated by their yellowred colour). Here, we reportt he first examples of bimetallic homogeneous 'TiO 2 -like' complexes utiliseda sv isible-light-activated photosensitisers in the generation of 1 O 2 .
The corresponding Ti IV complexes were formedu sing two differentm etal precursors; C1, C2, C4 and C5 were synthesised throught he deprotonation of the pro-ligands with NaH, followed by the additiono fT iCl 4 ,w hile C3 was formed via the direct addition of Ti(OiPr) 4 at ambient temperature. Coordination of the ligandst ot he Ti centre was confirmed via the splitting of N-methylene resonances (4.93-2.57ppm for C1)i nt he 1 HNMR spectra. The bimetallic nature of the complexes was corroboratedu sing ESI mass spectrometry and single crystal Xray crystallography.T he compounds werep urified via recrystallisation from diethyl ether or chloroform to give complexes C1-C5 with moderate to high yields (39-64 %) as yellow and red solids ( Figure 2).

Crystallography
Single crystals, suitable for X-ray diffraction studies, were grown via the slow evaporation of diethyle ther (C2 and C3), chloroform (C4)o rmethanol (C5)s olutions of the compounds. Using non-dried crystallisation solvents has reliably led to the formation of bimetallic complexes with TiÀOÀTi oxo-bridges.I n C5,t he propoxide groups on the Ti centres were displaced with methoxy ligandso riginating from the methanol solvent. Interestingly,f or ligands L1-L3,d ouble oxo-bridged bimetallic complexes( C1-C3)w ere formed, whereas for ligand L4,o nly single oxo-bridged complexes C4 and C5 were obtained. A range of procedures were exploredi na na ttemptt of orm equivalent complexes with all ligands, however,t he difference in the number of oxo-bridges persisted, regardless of the synthetic method or the crystallisation solventused.
All complexes exhibit ad istorted octahedral geometry aroundt he metal centres,w ith N2-Ti-O2 (C2 and C3)a nd O1-Ti-O2 (C4 and C5)b ond anglesr angingf rom 158.47(5)8 to 163.69(7)8.N otably,t he phenolate groups take up a cis arrangement, when ligandsw ith methylpyridine side-arms were used (L1-L3,F igure 3), whereas using L4,t he decreased steric bulk of the methoxyethyl side-arm favours the phenolate groups arrangedi natrans position ( Figure 4). Similar behaviour was observed in related Ti complexes investigated by Mountford and co-workers. [43] The metal-ligand bond lengths in the double-bridged complexes C2 and C3 are slightly longer than in complexes C4 and C5,w hich could be attributed to    the extra steric bulk of the methylpyridine side-arm and the presenceo ft he sterically strainedf our-membered ring. For example,i nC2,t he Ti-phenolate bond lengths are 1.9249(1) and 1.8827(1) ,w hereas in C4,t he corresponding values are 1.855(2) and 1.854(2) ,r espectively.O verall, the bond lengths and bond angles in all four novel bimetallic complexes are comparable to related Ti ABP derivatives reported in the literature. [44][45][46] UV-vis spectroscopy studies Solution phase UV-vis spectra of complexes C1-C5 were recorded using chloroform as the solvent in order to determine the absorption profiles of the compounds. The spectra of complexes (e.g. C4,F igure 5) show al arger absorption band at 280 nm, corresponding to the absorption maximum of the ligand,w hich was confirmed with control experiments (Figure S18). As econd, weakera bsorption band was observed at 378 nm, which corresponds to al igand metal charge transfer (LMCT). All dimericT ic omplexes exhibited as imilara bsorption maximum (332-378 nm, Ta ble 1), with significant response detectablei nt he visible region (> 400 nm), which wasa lso indicated by their yellow to red colour. Importantly,t his property allowed the photosensitisation experiments to be carriedo ut with irradiation at the wavelength of 420 nm, whicho ffers an advantage over traditionalT iO 2 catalysts, such as anatase, that does not absorb in the visible region.

Photocatalytic activity
Complexes C1-C5 were screened for activity as triplet photosensitisers in the generation of singlet oxygen using ac ommercial flow photoreactor under visible light (420 nm) irradiation. The activity was monitored via the photo-oxygenation reaction of a-terpinenet owards ascaridole, which only proceeds in the presence of 1 O 2 (Scheme 1). [47] All experiments werec arried out in CDCl 3 solventa sd euterated solvents are known to be beneficial for increased 1 O 2 lifetime and enablec onvenient sampling for the determination of conversion via 1 HNMR spectroscopy( FigureS20). [27,48] Ther eactionm ixtures were saturated with O 2 prior to the experiments andf low rates of both the substrates olution and ac ontinuous oxygen supply were kept constant at 1mLmin À1 .Aschematic of the flow reactor setup can be found in the supportingi nformation ( Figure S19).
Using 5mol %c atalyst loading, all five complexes showed good activity in the productiono f 1 O 2 at ambient temperature ( Figure 6). a-Terpinene was selectively converted to ascaridole, the formation of common by-products such as p-cymene was not detected in the reaction mixtures. [49] On the other hand, comparative studies using TiO 2 (P25) under identicalr eaction conditions afforded exclusively transformation into p-cymene as indicated by the appearance of an aromatic resonance at Scheme1.Synthesis of ascaridole from a-terpinene and competing side reactiont of orm p-cymene.  [a] Spectra wererecorded with 0.0003 m solution of the complexes in CHCl 3 at ambienttemperature. Figure 6. Conversion of a-terpinenetoa scaridole vs. time.
7.11ppm in the 1 HNMR spectra of reactionm ixtures. The lack of oxygenated products in these experimentsc onfirms that traditional TiO 2 catalysts are not suitable for 1 O 2 generation under visible light irradiation. Notably,c ontrol experiments in the absence of photosensitisers achievedalow conversiono f 4% in three hours, which can be attributed to the commonly observed self-sensitisation phenomenon. [34] These results highlight that the presence of the Ti complexes was essential for efficient 1 O 2 generation. The most active photosensitiser was complex C5,a chieving full conversion in two hours (Figure 7). Kinetic studies with samples taken at 15 minute intervals showedanear linear reaction profile, which revealed ap seudo first order dependence on substrate concentration,c omparable kinetic profiles were previously observed in the photo-oxygenation of a-terpinene. [50][51] Similar rates were observed using C1,whichreached full conversion of the a-terpinenei nt hree hours.W hile these reactionr ates generally fall below those achieved with precious metal (Re and Ir) photosensitisers, [32,[52][53] it is clearly demonstrated that these simple and stable Ti ABP complexes are capable to reach 1 O 2 generation activity levels comparable to TiO 2 and POT-based systems.
Complexes C2, C3 and C4 exhibit as lower rate in the first 30 minutes of the reaction, therefore full conversion is reached in up to four hours. This lag period suggested an initial transformationo ft hese photosensitisers into ad ifferent, catalytically species. However,t he photostability of C4 was investigated under 420 nm irradiation for 24 hours and the complex remained unchanged according to 1 HNMR spectroscopy studies. Furthermore, mass spectrometry analysiso ft he reactionm ixtures after the photocatalytice xperiment verified the presence of the initial bimetallic complexes. It was therefore concluded that the activep hotosensitisers were the dimeric TiÀOÀTi bridged structures. It appearst hat there is an acceleration in reactionr ate at higherc onversions, whichc an be attributed to ac ombination of different effects, such as some autocatalytic behaviour of the ascaridole formed, or the increased ratio of 1 O 2 versus a-terpinene.
With respect to structural properties, tert-butyl groupso n the ligands showedapositive impact on the productiono f 1 O 2 ,l ikely due to the increased solubility of these complexes (C1, C4, C5). Importantly,i tw as shown that the presence of the TiÀOÀTi moiety is crucial for the efficient photosensitisation: Controlr eactions with am onometallic complex (L1)TiCl 2 (Figure 8) only achieved 18 %c onversion in four hours cf. 100 %w as achieved in three hours with the bimetallic m-oxo-bridgeda nalogue C1. Moreover,t he remarkablec onversion achieved with C5 showed, that the activity is enhanced by the methoxy groups on the metal centres,w hichf urther extend the oxo-bridged framework. Control experiments revealed that the free pro-ligands (L1H 2 , L3H 2 and L4H 2 )a lso exhibit some catalytic activity under these reaction conditions, however,t hey yielded similarly low conversions(9-28 %a fter 4h). Figure 9c omparest he activities of C5 and the corresponding pro-ligand L4H 2 .E xperimentsw ithout oxygen bubbling showedt hat it is essential to have ac onstants upply of O 2 to achieve high conversions.

Computationals tudies
Each of the target molecules (C2-C5)w as optimised using CAM-B3LYP/6-311G(d,p) startingf rom the crystal structure coordinates.Ap olarizable continuum model (PCM) was used to model ac hloroform solvent (dielectric constant = 4.7113). Time-dependent (TD) CAM-B3LYP was used to determine the excited singlet and triplet electronic states. This has previously been shown to compare well to high-order correlated wavefunctionr esponse approaches, [54] and perform well in describing neutrala nd chargedT iO 2 clusters. [55] S 0 and T 1 states were optimised and the analytical Hessian wasc onfirmed as positive definite to verify the structures as minima. The nature of the

Chemistry-A European Journal
Full Paper doi.org/10.1002/chem.202001678 excited electronic states was determined using the response eigenvectors with the canonical Kohn-Sham orbitals. All computations werep erformed using al ocal version of Gaussi-an16. [56] All optimised geometries agree well with the crystal structures. The calculated absorption spectra agree reasonably well with the experimental resultsf or clusters of this size (with a general blue-shift). All excited states are very mixed with many LMCT transitions contributing to each state. The LMCT transitions are from p orbitals, localised on the aromatic units, to orbitals of Ti localised d-character mixed with higher p*o rbitals ( Figure 10).
The dominant particle-hole pair is shown in Table 2( for each molecule this is around 40-50 %o ft he state). There is a large density of low-lying electronic states and for all molecules the lowest excited state is generally aq uasi-degenerate pair of one bright and one dark state (Table 2). For C4 and C5 the brightest state is not this lowest pairb ut a( slightly) higher lying one. Each molecule C2-C4 has al ow-lying triplet state that is well separated from all other excited electronic states. All molecules show as imilar energy gap from this triplet to the ground state singlet. For each molecule the T 1 state has a significant component of HOMO-LUMO particle-hole character, and like the singlet manifold these involve LMCT (p/dp*) character.C onsistent with this the triplet states have elongated TiÀ Ob onds relative to the ground state structures but generally a similart opology.

Conclusions
In conclusion, as eries of five novel bimetallic TiÀOÀTi bridged amine bis(phenolate) complexes were synthesised and employed as photosensitisers in the generation of 1 O 2 .U nlike their heterogeneousT iO 2 -based counterparts, these soluble and well-defineda ggregates showed significant response to visiblel ight, which allowedt hem to be screened as photosensitisers in ac ommercial flow reactor under 420 nm LED irradiation. All complexes have efficiently converted a-terpinene to ascaridole between two to four hours of residence time, moreover excellent selectivity (> 99 %) towards ascaridole (vs. pcymene)w as achieved as confirmed via control experiments using TiO 2 .C omparative studies with the free pro-ligand and a monometallic analogue showed that the presenceo ft he 'TiO 2like' TiÀOÀTi moiety is crucial to achievee fficient photo-oxygenation. The LMCT states and singlet-triplet gaps for each complex were investigatedu sing computational methods, the calculated UV-vis absorption spectra agreed reasonably well with the experimental observations. These resultsh ighlight that smaller,m odular complexes of Ti IV can be competitive alternatives of the widely researched TiO 2 and POT photocatalyst systems. Moreover,f ine-tuning of the ligand design may extend the absorption furtheri nto the visible region, which would allow the utilisation of this inexpensive and non-toxic metal to replace Ru-and Ir-based catalysts in aw ider scope of photochemical reactions. The apparent interplay between activity and ligand substituents/bridges between the Ti centres will be furtheri nvestigated along with the breadthofr eactivity in photocatalysis that thesecomplexes can display.

Experimental Section
General considerations:S tarting materials were purchased and used as received from Merck, Acros and Fluorochem. Unless stated otherwise, experiments were carried out under ambient atmosphere. Dry solvents were purified in an MBRAUN SPS-800 and stored over activated 4 molecular sieves under ad ry N 2 atmosphere. NMR spectroscopy data was acquired with aB ruker AVIII 300 MHz instrument or Bruker AVIII 400 MHz instrument at 298 Ki n  CDCl 3 .E lectrospray ionisation mass spectrometry (ESI) was recorded using aB ruker micrOTOF II. Solution-state UV/Vis spectra were recorded on aS himadzu UV-2550 system with 10 mm quartz cuvettes.
C3 and C5:P ro-ligands L3H 2 and L4H 2 (1.0 mmol) were dissolved in THF (20 mL). Ti(OiPr) 4 (0.28 g, 0.30 mL, 1.0 mmol) was added and the solution was stirred for two hours. The solvent was removed under reduced pressure and the crude product was recrystallised from diethyl ether or methanol. Deposition Numbers 1992707 (C2), 1992708 (C3), 1992709 (C4), 1992710 (C5) contain the supplementary crystallographic data for this paper.T hese data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service.
Data for (L1)TiCl 2 :( L1)TiCl 2 (0.44 g, 69 %) was prepared according to literature procedures [43] for comparison of photosensitising properties. 1  Ltd.). As chematic of the flow experiment setup can be found in the supporting information ( Figure S19). Titanium complex (C1-C5) (12 mg, 5mol %) and a-terpinene (0.16-0.26 mmol) were dissolved in CDCl 3 (12 mL). The solution was saturated with O 2 for ten minutes. The solution was then pumped through the photochemical reactor at 1mLmin À1 .O 2 was pumped through as econd pump at the same flow rate, mixing with the solution at aT -junction before entering the photochemical reactor.S amples (450 mL) were taken at regular intervals. Crystallography:S ingle-crystal X-ray diffraction data were collected on aR igaku Oxford diffraction SuperNova diffractometer or a Bruker venture d8 diffractometer with CCD detector with Mo-Ka radiation (l = 0.7107 )o rC u-Ka radiation (l = 1.5418 ). The structures were solved by direct methods using SHELXS or SHELXT and refined by full-matrix least squares on F 2 using SHELXL interfaced through Olex2. [61][62] Molecular graphics for all structures were generated using Mercury.