Advances in heterometallic ring-opening (co)polymerisation catalysis

Truly sustainable plastics require renewable feedstocks coupled with efficient production and end-of-life degradation/recycling processes. Some of the most useful degradable materials are aliphatic polyesters, polycarbonates and polyamides, which are often prepared via ring-opening (co)polymerisation (RO(CO)P) using an organometallic catalyst. While there has been extensive research into ligand development, heterometallic cooperativity offers an equally promising yet underexplored strategy to improve catalyst performance, as heterometallic catalysts often exhibit significant activity and selectivity enhancements compared to their homometallic counterparts. This review describes advances in heterometallic RO(CO)P catalyst design, highlighting the overarching structure-activity trends and reactivity patterns to inform future catalyst design.

cation. Heterometallic complexes may also feature direct polar M-M′ bonds 12 , providing access to unique reactivities 3 .
Whilst heterometallic cooperativity has been well-studied in a range of organic transformations, heterometallic catalysis is still gathering momentum in polymerisation processes 7,13 . With increased demand for sustainable plastics, research into ringopening polymerisation (ROP) and ring-opening copolymerisation (ROCOP) to produce useful and degradable polymers has grown rapidly. Two of the most promising current strategies 14 are the production of poly(lactic acid) (PLA) via ROP of bioderived lactide (LA) 15 , and carbon dioxide (CO 2 )/epoxide ROCOP to form polycarbonates and polyurethanes 16 . The material properties are dictated by the polymer microstructure (e.g. chain length, dispersity and tacticity) and organometallic RO(CO)P catalysts have generally outperformed organocatalysts and enzymes in combining activity with polymerisation control 17 .
Heterometallic catalysts have the potential to revolutionise RO (CO)P by providing multiple and inequivalent catalytic sites for monomer activation and nucleophilic attack, which are key steps during initiation and propagation. The catalyst performance is controlled by the metals, ligand architecture and the polymerisation conditions. Importantly, not all metal combinations are cooperative. While isolated studies have been reported, this review identifies key structural motifs and overarching heterometallic activity trends across cyclic ester/carbonate ROP, epoxide and CO 2 /cyclic anhydride ROCOP and aziridine/carbon monoxide (CO) ROCOP (Fig. 1), in order to guide future heterometallic catalyst development.

Ring-opening polymerisation
Cyclic ester ROP is an efficient route towards degradable aliphatic polyesters with engineering, packaging 18 and biomedical applications 17,19,20 . Metal-catalysed ROP typically proceeds through a coordination-insertion mechanism with the catalysts comprising a Lewis acidic metal and a nucleophile (e.g. alkoxide/ amide) supported by sterically-hindered ligands 17,20,21 . While many homometallic ROP catalysts have been reported [21][22][23][24][25] , some multimetallic complexes (e.g. bis-Al, Hf, In, Mg, Ti, Y, Zn and Zr) have shown significant activity and selectivity enhancements [24][25][26][27][28] , and some of which have been proposed to operate via a chainshuttling mechanism 29,30 . There is a substantial opportunity to further improve catalyst performance through heterometallic cooperativity, and progress has already been made with heterocombinations from across the Periodic Table. While detailed mechanistic studies have not yet been reported for heterometallic complexes, experimental observations indicate that the larger and more electropositive metal acts as the monomer coordination site, and the more Lewis acidic metal acts as the source of the Malkoxide nucleophile 31 . Complexes where alkali metals (K/Li/Na) are combined with divalent (Mg/Zn) [31][32][33][34][35] , trivalent (Al/In/ Y) [36][37][38][39][40] or tetravalent (Ge/Sn) elements have been most prevalent in ROP 41 . Combining non-toxic and earth abundant metals such as Al, Mg and Zn with alkali metals is particularly appealing from both economic and environmental perspectives 42 .
Heterometallic Li/Mg complex 2 ( Fig. 2, Li-Mg distance = 2.67 Å), converted 55 equiv. rac-LA in 1 h with 1 equiv. MeOH in DCM at 20°C (Đ = 1.22) 33 . The experimental M n values were almost double those calculated, which was attributed to slow initiation via in situ generated Mg-Cl species (by reaction of Mg-n Bu with DCM). The mono-Mg complex displayed similar control (Đ = 1.12), however this catalyst required 2 h to convert 55 equiv. rac-LA under otherwise identical conditions. Lithium and sodium zincates 3a-b (Fig. 2) exhibited similar activity, polymerising 182 equiv. and 190 equiv. l-LA, respectively (toluene, 48 h, 90°C) 34 , with relatively good control (Đ = 1.42 and 1.26, respectively) and generating OH-terminated PLA chains. 3b was also active and controlled under non-anhydrous conditions, converting 87 equiv. l-LA in 48 h at 90°C (Đ = 1.33). This was attributed to the partial dissociation of 3b to form the mono-Na aryloxide complex in situ, with the latter shown to be more active in l-LA ROP (138 equiv. l-LA converted in 24 h, anhydrous conditions, Đ = 1.33), however the solution-state structures of 3a-b were not investigated. 3a generated only trace PLA under non-anhydrous conditions, which suggested that complete hydrolysis occurred. A trisphenol ligand was used to synthesise tetrametallic M 2 /Zn 2 and M 2 /Mg 2 (M = Li or Na) complexes 4a-d (Fig. 2) 35 . The additional Zn centre in 4b may enhance the activity vs. 3b (238 equiv. l-LA converted in 36 h at 110°C, Đ = 1.31) 34 , albeit direct comparison could not be made due to the different reaction conditions. We recently reported Na/Zn 2 and K/Zn 2 complexes 5a-b ( Fig. 2) for LA, ε-caprolactone (ε-CL) and δ-valerolactone (δ-VL) ROP 31 , which outperformed the homometallic counterparts by combining high activities (Na/K) with good control (Zn 2 ). In the presence of 2 equiv. benzyl alcohol (BnOH), 5b (K/Zn 2 ) converted 60 equiv. rac-LA in just 20 s (THF, room temperature, Đ = 1.40, k obs = 1.7 × 10 −2 s −1 ); to date, this is the fastest heterometallic catalyst system reported for LA ROP. NMR spectroscopy (including DOSY) and density-functional theory calculations suggested that 5a-b retain their heterometallic structures in the solution-state. 5a-b display improved activities in Lewis donor THF (vs. the analogous bis-Zn complex), and the fivefold activity increase in LA ROP upon switching Na (5a) for the larger K centre (5b) highlighted the key role of Na/K in LA coordination and activation. In both cases, incorporating Na/K also labilised the Zn-Et bonds (vs. the bis-Zn complex), as evidenced by NMR spectroscopy, accelerating the nucleophilic attack and LA ring-opening.
Alkali metal/trivalent metal heterocombinations. Stericallyhindered mono-alkoxide Li/Al complexes 6a-b (Fig. 2) were inactive, however the bis-alkoxide 6c-d analogues polymerised LA at room temperature 36 , which is uncommon for Al-based catalysts 23,26 . 6c-d were still relatively slow, converting 189 equiv. rac-LA in 16 h in DCM, albeit with good control (Đ = 1.03) 36 compared to other Group 1 catalysts 23 . The enhanced activity of 6c-d vs. Al-based catalysts was tentatively attributed to their in situ dissociation to [(RN-o-C 6 H 4 ) 2 O)Al(OBn)] (R = C 5 H 9 or Cy) and LiOBn. However, these monometallic counterparts were inactive under the conditions employed with 6c-d, providing evidence for cooperative Li/Al operation in 6c-d.
Preliminary results with M/Al complexes 7a-c (M = Li, Na, K respectively, Fig. 2) indicated that 7a and the analogous bis-Al complex were more active than 7b-c in ROP 37 . 7a and the bis-Al analogue converted 78 and 75 equiv. l-LA, respectively, whereas 7b-c polymerised 48 and 20 equiv. l-LA, respectively (1 equiv. BnOH, 5 h, 125°C, toluene). The higher activity of 7a vs. 7b-c was not specifically addressed but deviates from the activity trend commonly observed for Group 1 ROP catalysts (Li + < Na + < K + ), where larger metals typically enhance monomer coordination thus polymerisation activity 44 . NMR analysis indicates the (L)Al-Me 2 groups are more nucleophilic in 7a-c than in the bis-Al species. The activity differences observed suggest a combination of multiple factors are important, including the metals, ligand and solution-state structures.
In comparison to 8, the Li/Y complex 9 (Fig. 2) exhibited higher activity in ROP without an alcohol (BnOH), converting 225 equiv. rac-LA to form heterotactic PLA (P s = 0.99) in 5 h at 30°C in THF (vs. 68 equiv. in 7 h at 70°C with 1 equiv. BnOH) 39 . DOSY NMR analysis confirmed the heterometallic structure of 9 in THF solvent. Initiation was proposed to occur via nucleophilic attack from the ligand of 9 based on SEC, 1 H NMR spectroscopy and MALDI-ToF analysis.
Alkali metal/tetravalent metal heterocombinations. The Li/Ge complex 10a (Fig. 2) was almost twice as active as the mono-Ge analogue in l-LA ROP (57% vs. 35% PLA yield, respectively; 500 equiv. l-LA, 10 equiv. i PrOH, 6 h, 100°C), which may arise from Li + enhancing l-LA coordination 41 . In contrast, the Li/Sn complex, 10b, was slower than the homometallic mono-Sn analogue, which was attributed to the higher moisture-and air-sensitivity of the former and possible catalyst decomposition during ROP.
Divalent/trivalent metal heterocombinations. The Al/Zn complex 11 (Fig. 2) was more active than the analogous mono-Al and bis-Al complexes in ε-CL ROP 45 , resulting in 95% PCL yield in 6 min at 70°C (2:1:100 BnOH:catalyst:ε-CL) 46 . It was, however, slower than the bis-Zn analogue 45 , which produced 98% PCL in 1 min under the same conditions suggesting that Zn is more catalytically active than Al in 11 46 . The higher activity of Zn was attributed to the lower bond dissociation energy of Zn-O (284 kJ mol −1 ) vs. Al-O (512 kJ mol −1 ); M-OR bond cleavage is a key step in ROP.
Our group reported Al/Zn and Mg/Al complexes 12a-b 40 , which displayed good catalyst activities in rac-LA ROP, outperforming the mono-Al analogue by respective factors of two and 11 under identical conditions (12a, k obs = 1.8 × 10 −3 s −1 ; 12b, k obs = 8.8 × 10 −3 s −1 ; mono-Al k obs = 0.8 × 10 −3 s −1 ; toluene, 120°C, 1:50:100 catalyst:propylene oxide (PO):rac-LA. The mono-Zn and mono-Mg analogues were completely inactive under the same conditions, while Ca/Al and Li/Al complexes 12c-d displayed lower activities than the mono-Al complex. Based on kinetic and computational studies (including ab initio molecular dynamics calculations), the high activity of 12a-b was attributed to close intermetallic proximity, increased ligand strain and the rigid square pyramidal geometry around the Al centre (highest with 12b), leading to improved monomer coordination. In addition, the Lewis acidity of Mg and Zn led to bridging Mg-or Zn-Cl-Al moieties thus longer and weaker Al-Cl bonds in 12a-b (vs. mono-Al), which correlated with faster initiation (induction periods were 1, 3 and 4 min for 12a,b and mono-Al, respectively).
Transition metal/main group heterocombinations. Main group/transition metal heterometallic ROP catalysts have so far focused on titanium, an attractive, non-toxic, inexpensive and abundant metal 47,48 . The development of heterometallic zirconium and hafnium catalysts offers an interesting area for future development, as both metals have excellent precedent in ROP 49,50 . The M/Ti(IV) complexes 13a-d (M = Li, Na, Zn, Mg; Fig. 3) are efficient initiators for l-LA ROP in toluene at 30°C 47 . The alkali metal-containing 13a-b exhibited similar activity to the mono-Ti(IV) complex (76 equiv. l-LA converted in 94 h at 30°C), despite X-ray crystallography of 13a indicating increased Ti Lewis acidity, with longer and weaker (more nucleophilic) Ti-(O i Pr) 2 bonds. Significant rate enhancements were however observed with 13c-d, with 13c (Zn/Ti) polymerising 91 equiv. l-LA within 30 min and 13d (Mg/Ti) converting 89 equiv. l-LA in 3.5 h with good control (Đ = 1.27 (13c), 1.28 (13d)). The higher activity of 13c vs. 13d was originally attributed to the lower charge density of Zn than Mg resulting in weaker Zn-OR bonds than Mg-OR. However, due to the similarity in the ionic radii and charge (Zn 2+ = 74 pm, Mg 2+ = 72 pm) 51 , other factors such as the higher Lewis acidity and oxophilicity of Mg (Ɵ = 0.6) vs. Zn (Ɵ = 0.2) are likely to be key factors in explaining the metalalkoxide bond strengths 52 .
Complex 14 bears a tetradentate ligand framework, and incorporation of Na was shown to increase the Ti Lewis acidity and weaken the Ti-O i Pr bonds (Fig. 3) 48 . Whilst only trace PCL was formed with the mono-Ti(III) and Ti(IV) analogues, 14 converted 182 equiv. ε-CL in 1 h (toluene, 60°C), albeit with low polymerisation control (Đ = 2.5).
F-block metal-based heterometallic complexes. ROP catalysts featuring f-block metals have also been developed to take advantage of their oxophilicity, Lewis acidity and large coordination spheres. Evidencing the role of lanthanide (Ln) metals in monomer activation, the activity of Na/Ln clusters ([Ln 2 Na 8 (OCH 2 CF 3 ) 14 (THF) 6 ] , Ln = Sm, Y, Yb; 15a-c, respectively) 53 in ROP directly reflects the Ln ionic radius: 15a > 15b ≈ 15c for ε-CL and 15a > 15b > 15c for trimethylene carbonate (TMC) ROP. Notably, 15a converted 3840 equiv. ε-CL in 30 min whereas only trace PCL formed with 15b-c at [ε-CL]:[catalyst] loading of 4000:1. 15a showed extraordinary activity for TMC ROP, converting 4000 equiv. in 1 min at 25°C (Đ = 1.44). Heterometallic 15a-c exhibited higher activity than the homometallic Ln phenoxide clusters and Na(OCH 2 CF 3 ) 54 . The enhanced activity of 15a-c was attributed to Na/Ln cooperativity via concurrent monomer activation and rapid ligand exchange. Moderate polymerisation control (Đ = 1.4-1.7) and shorter than expected M n values were linked to initiation via multiple Ln-OCH 2 CF 3 bonds and transesterification. 15a-c were more active in toluene than in THF, which may suggest modification of the cluster structure in THF.
Similar trends were observed with Li 2 Ln 2 (Ln = Y, Er, Eu and Sm) complexes 16a-d ( Fig. 4) 55 , with an activity decrease in l-LA ROP with decreasing Ln radius (16d > 16c > 16b ≈ 16a). Complexes 16a and 16d were more active than the mono-Y and Sm analogues, which was tentatively attributed to reduced steric hindrance around Ln in 16a,d. NMR analysis also suggested 16a is more flexible than mono-Y, with the piperazidine ring in a chair conformation rather than a boat conformation. Similarly to clusters 15a-c, 16a-d showed higher activity and control in toluene than THF, which may indicate structural differences in Lewis donor solvents. Indeed, 16c generated 98% PLA in toluene and 83% PLA in THF (30 min, 60°C, [LA]:[Ln] = 1000:2), producing PLA with shorter than expected M n in THF. It is plausible that 16a-d dissociate in coordinating solvents to generate multiple initiating species, and/or that THF coordination to Li/Ln may inhibit monomer coordination 56 . The Li/Th (IV) complex 17 (Fig. 4) is the only actinide-based heterometallic ROP catalyst reported to date 57 . It displayed relatively low activity and polymerisation control, converting 48 equiv. L-LA in 2 h (toluene, 30°C) with a bimodal M n dispersity (Đ = 1.63).
Ln-based heterometallic ROP complexes have also been extended beyond alkali metals to Al 58 , Mg 59 and Ni 60 . Heterometallic Ln/Al (Ln = Y, Sm) complexes 18a-d (Fig. 4) were studied in rac-LA ROP 58 . While 18a showed activity and control enhancements compared to the mono-Al and Y counterparts, converting 123 equiv. rac-LA in 5 h at 20°C in toluene (Đ = 1.95), the reactivity of 18a was further improved by addition of 5 equiv. hexamethyldisilazane (as a chain-transfer agent) or by alcoholysis with i PrOH. The alkoxide analogues 18c-d were highly active and both converted 495 equiv. rac-LA in 30 min with moderate control (Đ = 2.32 and 1.70, respectively). Strikingly, 18d polymerised 1820 equiv. rac-LA in 1 h at 20°C in toluene (Đ = 1.72), generating high M n PLA (69 100 g/mol). The Al centre in 18a-d was proposed not to be directly involved in ROP due to the low activity of mono-Al species (vs. 18c-d), however Al may modulate the activity of Ln through electronic communication via the bridging O atom.
The activity of Ln/Mg allyl complexes 19a-b (Ln = La or Y, respectively, Fig. 4) was explored in ε-CL and rac-LA ROP 59 . 19a outperformed 19b, converting 198 equiv. ε-CL in 20 s at 20°C and 85 equiv. rac-LA in 2 h at 40°C with good control (Đ < 1.4). While 19b converted 122 equiv. ε-CL in 1.3 min at 20°C, it was inactive for rac-LA ROP. The lower activity of 19b was attributed to the smaller size of Y 3+ (90 pm, vs. La 3+ , 103 pm). Both complexes initiated ROP via nucleophilic attack of the allyl moiety on the coordinated monomer, as evidenced by 1 H NMR spectroscopy.
Heterometallic Ln/Ni(II) complexes 20a-g (Fig. 4, Ln = Ce, Nd, Sm, Eu, Tb, Ho and Tm) were tested for l-LA ROP 60 , however despite the improved control, all were less active than mono-Ni species. This was attributed to the Ln(NO 3 ) 3 moiety occupying the outer O 2 O 2 salen cavity thus sterically hindering the monomer approach to Ni in the N 2 O 2 core. Indeed, 20b displayed the longest Ln-Ni distance (3.48 Å) and showed the highest activity, converting 730 equiv. l-LA in 24 h at 130°C (Đ = 1.12).
Key activity trends in ROP. Across heterometallic ROP studies, enhanced activity with larger and more Lewis acidic metals featuring more open coordination geometries emerges as one of the most prevalent trends. The highest activities are generally observed with medium/large metals, e.g. alkali metals and lanthanides, attributed to larger coordination spheres enhancing monomer coordination and activation. Combining Lewis acidic metals with more electronegative metals with weaker M-OR bonds may accelerate coordination and nucleophilic attack. Heterometallic complexes based on Al/Zn 46 , K/Zn 31 , La/Mg 59 , Li/ In 38 , Li/Mg and Li/Zn 32 , Li/Sm 55 , Mg/Al 40 , Na/Sm 53 , Na/Zn 31 , Sm/Al 58 and Ti/Zn 47 have all displayed superior activities compared to the homometallic analogues. Most of these complexes feature a M-O-M′ framework, enabling intermetallic electronic communication and/or "ate"-type activation (vide supra), which can lead to enhanced nucleophilicity of the M-R bond (e.g. R = alkoxide) 38,47,48,58 . Despite these promising results, future ROP studies should explore the solution-state structure of heterometallic catalysts to confirm that the enhanced activities can be accredited to heterometallic cooperativity. Heterometallic catalysts should also be benchmarked against all homometallic counterparts to fully understand when heterometallic cooperativity leads to an activity enhancement.
While ROP provides a convenient route to access aliphatic polyesters and polycarbonates, these materials can also be accessed via epoxide ROCOP with cyclic anhydrides or CO 2 , respectively. ROCOP provides access to a broader scope of material properties due to the greater monomer structural diversity, and there is a growing interest in heterometallic ROCOP catalyst design. Owing to the mechanistic similarities between ROP and ROCOP, both of which include monomer coordination, nucleophilic attack and ring-opening, catalysts employed for these processes are often structurally-alike; some catalyst systems have demonstrated impressive activities in both 56,[61][62][63][64][65][66] . Advances in heterometallic ROP catalysis may therefore inform future understanding and design of heterometallic ROCOP catalysts and vice versa.
Ring-opening copolymerisation. Epoxide ROCOP with CO 2 or cyclic anhydrides displays sustainability benefits, as CO 2 may be sourced from industrial waste streams 16,67,68 , and some epoxides and anhydrides can be derived from biomass (e.g. limonene/αpinene oxide, succinic/citraconic anhydrides) 69,70 . Life cycle analysis has suggested that incorporating CO 2 into polyol production (for subsequent polyurethane synthesis) can reduce petrochemical consumption by 20% and CO 2 emissions by 19% compared to conventional polyol synthesis 71 .
Catalyst design has enabled the generation of nearly perfect polycarbonates (>99% carbonate linkages) through ROCOP, by overcoming the undesired formation of polyether linkages and cyclic carbonates 70,72 . Most catalyst systems reported are homometallic and often multimetallic 64,70,73 , including bis-Co (II) 74 , Co(III) 75,76 , Fe(III) 77 , Mg(II) 67 and Zn(II) complexes [78][79][80][81][82][83] . Studies have pointed towards a bimetallic mechanism, which limits the use of dimeric catalysts with high monomer loadings or at high dilutions. Intermetallic proximity in the range of 3-5 Å is generally optimal for improved catalyst performance, which has directed ligand design towards dinucleating scaffolds 77,84 . Mechanistic studies on homobimetallic complexes suggest that both metals are involved in ROCOP, and hint that heterometallic catalysts could further improve activities by enhancing both epoxide coordination (Lewis acidic/electrophilic metals) and the nucleophilicity of the metal-carbonate bond. Examples of heterobimetallic catalysts that combine main group, transition and Ln metals have recently been reported.
With 23e-f, epoxide activation on Mg or Ca (respectively) was proposed as X-ray crystallographic studies showed THF coordination to these metals. Heterometallic 23e (Mg/Zn) displayed a TOF of 72 h −1 and was six times more active than LZn 2 I 2 (0.1 mol% catalyst loading, neat epoxide, 1 bar CO 2 , 80°C). However, all other heterocombinations investigated were less active than LZn 2 I 2 . As well as the heterometal selected, the ligand conformation and the intermetallic separation may also play a role, as these differed with Li (23b, "crown-shape"; Zn-Li = 2.86 Å), Mg (23e, "bowl-shape"; Zn-Mg = 3.06 Å) and Ca (23 f, "S-shaped"; Zn-Ca = 3.35 Å). Interestingly, only 23b,d-e were selective for polycarbonate formation (>96%), with 23a,c,f generating cis-cyclic carbonates (>99%). Cyclic carbonate formation was linked to the iodide lability and potential dissociation of the growing polymer chain from the metal due to the increased ionic character of the metal carbonate bond 92 .
The importance of the metal combination in CHO/CO 2 ROCOP was also evident with complexes 24a-c 91 , where L adopts a "bowl" conformation with three chloride co-ligands. Heterometallic 24a-c were less active and selective than LZn 2 Cl 2 (TOF = 9 h −1 , 0.1 mol% catalyst loading, neat epoxide, 1 bar CO 2 , 80°C), with significant polyether formation (up to 32%). Increasing the CO 2 pressure to 20 bar led to a perfectly alternating polycarbonate with 24c, suggesting that CO 2 insertion may be implicated in the rate-limiting step, unlike L-based bis-Zn and Mg/Zn complexes, which are generally zero-order in CO 2 82,88 . The CO 2 uptake (Al < Ga < In) increased with the decrease in the Lewis acidity of the Group 13 metal 91 . This observation, along with the increased lability of the metal-alkoxide intermediates, was used to explain the activity increase from Al (TOF = 1 h −1 ) to In (TOF = 9 h −1 ). These features also outweighed the influence of intermetallic proximity on the activity of 24a-c, with both the distance and activity increasing on descending Group 13 (Zn-Al = 3.02 Å, Zn-Ga = 3.12 Å, Zn-In = 3.15 Å).
The Mg/Co complex 26 (Fig. 5) recently outperformed all Lsupported heterometallic complexes in CHO/CO 2 ROCOP, with TOF of 455 h −1 at 1 bar CO 2 pressure (0.1 mol% catalyst loading, neat epoxide, 80°C), > 99% carbonate linkages and good polymerisation control (Đ = 1.13) 93 . Under identical conditions, 26 was almost five times more active than 22 h (Mg/Zn), suggesting that Co is more active than Zn in ROCOP. 26 was also twice as active as LCo 2 (OAc) 2 , and three times faster than LMg 2 (OAc) 2 (0.1 mol% catalyst loading, neat epoxide, 1 bar CO 2 , 120°C).  93 . This was attributed to the lower bond directionality of Mg, possibly resulting in increased degrees of freedom during epoxide coordination. 26 was therefore proposed to catalyse ROCOP via a chain-shuttling mechanism (Fig. 6) with CHO coordination to Mg, followed by ringopening via the Co-carbonate bond.
The M/Co complexes 27a-d (M = Na, K, Rb or Cs, respectively) were recently reported as the first heterometallic catalysts to exhibit good turnover numbers for PO/CO 2 ROCOP 94 . 27b (K/Co) was most active, displaying TOF of 340 h −1 vs. 27a (TOF = 120 h −1 ), 27c (TOF = 54 h −1 ) and 27d (TOF = 47 h −1 ) in neat PO (0.025 mol% catalyst loading, 50°C,  20 bar CO 2 pressure). Monomodal SEC traces were obtained in the presence of >50 equiv. of 1,2-cyclohexane diol as a chaintransfer agent, with controllable M n values between 1.3 and 79.6 kg/mol. 27b also displayed an outstanding TOF of 800 h −1 (0.025 mol%, 70°C, 30 bar CO 2 pressure), with narrow dispersity (Đ = 1.07), >99% CO 2 uptake and 93% polycarbonate selectivity. The highest activity of 27b was attributed to the optimal combination of metal sizes and binding affinities. While smaller Na may be coordinatively saturated by the crown ether, preventing PO coordination, the larger Rb and Cs in 27c-d prevent coplanar incorporation into the macrocycle and form aggregate structures. From the kinetic data, the rate-determining step was proposed to involve ring-opening of K-coordinated PO by a Co(III)-carbonate intermediate via a chain-shuttling mechanism akin to other heterometallic catalysts (Fig. 6). Notably, 27b was also more than twice as active as Mg/Co complex 26 in CHO/CO 2 ROCOP (k p = 31.7 mM −1 s −1 at 50°C for 27b and k p = 15.1 mM −1 s −1 for 26 at 60°C).
The Ln/Zn complexes 30a-c (Fig. 7, Ln = Y, Nd or Sm, respectively) displayed moderate activity and selectivity in CHO/CO 2 ROCOP 97 . The most active complex, 30a, required 24 h to generate 71% polycarbonate (toluene, 30 bar CO 2 , 70°C) but outperformed the homometallic Y complex, which showed negligible activity. High CO 2 pressures were required for polycarbonate synthesis; only 16% polycarbonate was formed with 30a at ambient pressure, and the poor polymerisation control of 30a-c (Đ = 8.42-9.50) was attributed to polymer degradation and cyclic carbonate/polyether formation.
Studies of Ln/Zn complexes 32a-j (Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Fig. 7) in CHO/CO 2 ROCOP highlight the importance of the anionic co-ligand, as well as the Ln size 98 . While acetate complex 32a exhibited TOF = 230 h −1 and generated polymers with >99% carbonate linkages, the nitrate analogue 32b formed trace polymer and trifluoroacetate complex 32c favoured polyether formation (neat epoxide, 10 bar CO 2 , 100°C). The higher activity of 32a was attributed to the rapid exchange of the coordinated and outer-sphere acetate anions. The highest catalyst activities and selectivities were observed with 32a-f, which featured larger Ln metal centres than 32g-j. 32d (Ce/Zn) showed the highest activity with TOF = 370 h −1 (Đ = 1.3).
All Ln/Zn complexes reported for CHO/CO 2 ROCOP were proposed to operate via a chain-shuttling mechanism (Fig. 6), with the Lewis acidic Ln metal activating CHO for nucleophilic attack by the labile Zn-carbonate, formed via CO 2 insertion into the Zn-alkoxide bonds. Due to mechanistic similarities, it is plausible that the heterometallic cooperativity of catalysts reported for epoxide/CO 2 ROCOP could be extended to epoxide/cyclic anhydride ROCOP, to form a series of polyesters by switching the carbonyl source 70 .
Key activity trends in ROCOP. The nature of the metal combination and the initiating nucleophile are key in epoxide/CO 2 , epoxide/anhydride and aziridine/CO ROCOP. Generally, the different metals are proposed to adopt distinct roles, with the more Lewis acidic metal(s) activating the monomer(s) and the more labile metaloxygen bonds accelerating nucleophilic attack 63,86,88,90,91,93,95 . While many heterometallic complexes have led to enhanced activities, selectivities and polymerisation control, not all heterocombinations give improved performance, and a careful balance of Lewis acidity and M-OR bond polarity is required. Similarly to the trend observed in ROP, the catalytic activity of Ln-based heterometallic catalysts in ROCOP is often linked to Ln size; Ln with medium/large ionic radii (e.g. Ce and Sm) generally increase epoxide coordination and catalyst activity [96][97][98] . Notably, most heterometallic ROCOP catalysts operate without a co-catalyst, enabling the synthesis of high molar mass polymers, albeit often with the aforementioned bimodal dispersity.
Summary and outlook. In both ROP and ROCOP, heterometallic catalysts have displayed reactivity enhancements by facilitating concurrent monomer activation and nucleophilic attack. However, not all heterometallic combinations improve catalyst performance. Whilst more studies are required to fully understand and predict cooperative heterocombinations, key RO(CO)P catalyst features have started to emerge, including the metal size and coordination number, M-OR bond strength, M-M′ proximity, and the solution-state catalyst structure under polymerisation conditions. Pairing a hard metal (M, e.g. Group 1, 2 and Ln) with a softer, more carbophilic metal (M′, e.g. Co and Zn) can result in anionic "ate" activation, with the transfer of anionic ligands to the more carbophilic metal. For example, complexes 3a-b and 4a-d bear structures typically referred to as higher order zincates/magnesiates, where the central carbophilic Zn 2+ /Mg 2+ is surrounded by four anionic ligands. While not all of the complexes discussed herein bear typical "ate" structures, almost all feature a bridging M-O-M′ unit that enables electronic communication between the two metal centres. This electronic communication has the potential to form complexes with at least a partial "ate" character, with the tug of war of electron density between M and M′ lying to the side of M′. This unequal sharing of the electron density may simultaneously increase the Lewis acidity of the M centre and also the nucleophilicity of the M′-R group (where R = e.g. an alkoxide); both are key catalyst features in ROP and ROCOP.
The concept of heterometallic cooperativity has been relatively well-exploited with heterometallic complexes in epoxide/CO 2 ROCOP, where the two metals typically adopt different roles of epoxide coordination and nucleophilic attack from a metalcarbonate group in the chain-shuttling mechanism. The larger Lewis acidic metal (e.g. K, Mg or Ln) usually enhances Lewis donor (e.g. monomer) coordination, as observed by the preferential coordination of THF to Mg in 23e (Mg/Zn) 90 and MeOH/H 2 O to the Ln centre in 28a-f (Ln/Co) 95 in the molecular structures. Studies with 26 (Mg/Co) and 27b (K/Co) suggest that the more Lewis acidic Mg/K enhances the role of epoxide coordination, whereas the more electronegative metals (e.g. Co and Zn) typically accelerate the nucleophilic attack and epoxide ring-opening 93,94 , lowering the transition state barriers vs. the homometallic counterparts. Many of the reported heterometallic ROCOP catalysts feature heterometals in close proximity, Fig. 8 Proposed aziridine/CO ROCOP mechanism for Co/Pd catalyst systems. Proposed heterometallic mechanism for complexes 34a-g along with targeted poly(β-peptide) product and potential side-products from aziridine/CO ROCOP 109 . typically within the 3-5 Å range proposed to be crucial for effective bimetallic electronic communication and the chainshuttling ROCOP mechanism 77,84 . Catalysts designed for cyclic ester/cyclic carbonate ROP and CO 2 /epoxide ROCOP share several key features, including the Lewis acidity of the metal and nucleophilicity of the M-O(polymer) bond. Studies on bimetallic ROP catalysts suggest that intermetallic proximity can also be important, however further mechanistic investigations are required. While the individual heterometal roles are less well understood in ROP, the highest activities have been observed with complexes where medium/large Group 1/Ln metals are combined with Zn. Complexes comprising larger Lewis acidic Group 1/2/Ln metals have generally displayed superior activities, attributed to the presence of additional monomer coordination sites. Based on the mechanistic similarities between ROP and ROCOP, it is plausible that in the presence of heterometallic complexes, ROP also proceeds via Lewis acidic activation of the monomer by the Group 1/Ln metals, followed by nucleophilic attack and monomer insertion at the more electronegative M′-OR bond. This hypothesis is supported by structural analysis showing THF coordinated to alkali metals in 2, 3a-b, 4a-d, 5a-b, 6a-d, 13a-b, 14 and 16a-d and to Ln metals in 18a-d.
Heterometallic catalyst performance is also influenced by the reaction conditions; the solvent (or monomer) may alter the complex aggregation state or promote the in situ formation of solvent separated ion pairs. Throughout heterometallic RO(CO)P, there are examples where THF solvent decreases the catalyst activity, and further studies are required to understand whether this stems from increased M-M′ distances (by in situ modification of solution-state heterometallic structures) and/or competitive THF metal coordination blocking the monomer approach. Understanding whether heterometallic complexes maintain their structure in the solution-state is therefore crucial.
Alkali and Ln-based heterometallic catalysts have typically led to high activities in RO(CO)P, and there is scope for catalyst development with di-, tri-and tetravalent metal heterocombinations. Many of the heterometallic systems reported thus far have also been investigated under different reaction conditions, which makes comparisons challenging. This is especially prominent in ROP, and thus systematic studies are required to identify superior and inferior heterocombinations.
Heterometallic cooperativity has the potential to shape future RO (CO)P catalyst design. At present, heterometallic catalyst performance often falls short of the homometallic frontrunners, however there has been far more extensive research into homometallic catalysts, with >100 homobimetallic examples reported for LA ROP (vs. 39 heterometallic catalysts). While heterometallic catalyst synthesis is sometimes regarded as challenging, different methodologies including sequential deprotonation, coordination and/or transmetalation reactions, and reactions with preformed "ate" complexes have been successfully employed to prepare heterometallic complexes. Promisingly, we are now reaching a turning point, with a recently reported Mg/Co system now amongst the most active epoxide/CO 2 ROCOP catalysts at atmospheric CO 2 pressure. More recently, DFT calculations have been used to understand which catalyst features lead to heterometallic cooperativity in RO(CO)P, and there are exciting opportunities to use computational approaches to both understand and predict cooperative heterometallic catalysis in the future. The studies described here signal clear directions for understanding and exploiting heterometallic cooperativity within RO(CO)P catalysis.