Second-sphere Interactions Research Articles

Second-sphere interactions promote antenna effects for selective sensing of DPA in TbIII-based organic frameworks

Investigating the emission patterns of Ln-metal-organic frameworks (MOFs) is crucial but challenging for rational design and selecting suitable MOFs. Firstly, theoretical calculation was used to predict the energy transfer efficiencies between the central ions (Eu3+/Tb3+) and the ligand (H3BTTC). The result indicates that Eu3+ can be completely sensitized and therefore Eu-BTTC with high energy transfer efficiency shows single-emission, whereas Tb3+ can only be partially sensitized and Tb-BTTC shows dual-emission due to reverse energy transfer. Subsequently, Eu-BTTC and Tb-BTTC with heterogeneous emission properties were successfully constructed. In order to investigate the emission modes of the two LnMOFs, 2,6-dipyridyl acid (DPA) was chosen as the second sphere and triggered the interaction between DPA and MOFs. In Eu-BTTC, the fluorescence remained constant before and after the addition of DPA due to the Eu3+ sensitized completely. In Tb-BTTC, the interaction between MOF and DPA improves the energy transfer efficiency from BTTC to Tb3+, resulting in the fully sensitization of Tb3+ and a significant enhancement of the fluorescence of Tb3+. In response to these results, a series of experiments as well as theoretical simulations were conducted to reveal the mechanism. A rational design mode and a novel sensing mechanism for the sensing platform of Ln-MOFs was provided by this study.

Leveraging Triphenylphosphine-Containing Polymers to Explore Design Principles for Protein-Mimetic Catalysts.

Complex interactions between noncoordinating residues are significant yet commonly overlooked components of macromolecular catalyst function. While these interactions have been demonstrated to impact binding affinities and catalytic rates in metalloenzymes, the roles of similar structural elements in synthetic polymeric catalysts remain underexplored. Using a model Suzuki-Miyuara cross-coupling reaction, we performed a series of systematic studies to probe the interconnected effects of metal-ligand cross-links, electrostatic interactions, and local rigidity in polymer catalysts. To achieve this, a novel bifunctional triphenylphosphine acrylamide (BisTPPAm) monomer was synthesized and evaluated alongside an analogous monofunctional triphenylphosphine acrylamide (TPPAm). In model copolymer catalysts, increased initial reaction rates were observed for copolymers untethered by Pd complexation (BisTPPAm-containing) compared to Pd-cross-linked catalysts (TPPAm-containing). Further, incorporating local rigidity through secondary structure-like and electrostatic interactions revealed nonmonotonic relationships between composition and the reaction rate, demonstrating the potential for tunable behavior through secondary-sphere interactions. Finally, through rigorous cheminformatics featurization strategies and statistical modeling, we quantitated relationships between chemical descriptors of the substrate and reaction conditions on catalytic performance. Collectively, these results provide insights into relationships among the composition, structure, and function of protein-mimetic catalytic copolymers.

Hydroxypyridine/Pyridone Interconversions within Ruthenium Complexes and Their Application in the Catalytic Hydrogenation of CO2

Reaction of a new ligand 6-DiPPon (6-diisopropylphosphino-2-pyridone) with 0.5 equiv of [RuCl2(p-cymene)]2 resulted in the formation of a mixture of [RuCl2(p-cymene)(κ1-P-6-DiPPon)]2 (1) and [RuCl(p-cymene)(κ2-P,N-6-DiPPin)]Cl ([2]Cl) (where 6-DiPPin = 6-diisopropylphosphino-2-hydroxypyridine). The ratio between the two products can be controlled by the nature of the solvent. The similar reaction between 6-DiPPon and [RuCl2(p-cymene)]2 in the presence of AgOTf and Na[BArF24] (where BArF24 = [{3,5-(CF3)2C6H3}4B]-) resulted in the formation of the complexes [RuCl(p-cymene)(κ2-P,N-6-DiPPin)]OTf, ([2]OTf) and [RuCl(p-cymene)(κ2-P,N-6-DiPPin)]BArF24 ([2]BArF24), respectively. Reactions between complex [2]Cl, [2]OTf, or [2]BArF24 and a base (either DBU or NaOMe) resulted in the deprotonation of the hydroxyl functional group to form a novel neutral orange-colored dearomatized complex, 3. The identity of complex 3 was confirmed as [RuCl(p-cymene)(κ2-P,N-6-DiPPon*)], where 6-DiPPon* is the anionic species (6-diisopropylphosphino-2-oxo-pyridinide), which contains the deprotonated moiety. The new 6-DiPPon ligand and its corresponding air stable half-sandwich derivative ruthenium complexes 1, [2]OTf, [2]BArF24, and 3 were all isolated in good yields and fully characterized by spectroscopic and analytical methods. The interconversions between the neutral and anionic forms of the ligands 6-DiPPon, 6-DiPPin, and 6-DiPPon* offer the potential for novel secondary sphere interactions and proton shuttling reactivity. The consequences for this have been explored in the activation of H2 and the subsequent catalytic hydrogenations of CO2 into formate salts in the presence of a base.

Synergy of first- and second-sphere interactions in a covalent organic framework boosts highly selective platinum uptake

Synergy of first- and second-sphere interactions in a covalent organic framework boosts highly selective platinum uptake

Reactivity and Enantioselectivity in NHC Organocatalysis Provide Evidence for the Complex Role of Modifications at the Secondary Sphere

Secondary-sphere interactions are often harnessed to control reactivity and selectivity in organometallic and enzymatic catalysis. Yet, such strategies have only recently been explicitly applied in the context of organocatalytic systems. Although increased stability, reproducibility, and selectivity were obtained in previous work using this approach, the precise mechanistic pathway promoted by secondary-sphere modification in organocatalysis remained unclear. Herein, we report a comprehensive mechanistic study on the origin of the unique reactivity patterns and stereocontrol observed with boronic acids (BAs) as secondary-sphere modifiers of N-heterocyclic carbene (NHC) organocatalysts. Kinetic experiments revealed partial order in catalyst upon the addition of BA and unusual preactivation behavior, indicating the presence of stable off-cycle catalyst aggregation and BA-base adducts. These hypotheses were supported both by computations and by a series of NMR and nonlinear effect experiments. Furthermore, computations indicated a rate-limiting, water-assisted hydrogen atom transfer mechanism. This finding led to a considerable enhancement in the experimental reaction rate while maintaining excellent enantioselectivity by adding catalytic amounts of water. Finally, computations and racemization experiments uncovered an uncommon Curtin-Hammett-controlled enantioselectivity in the presence of secondary-sphere modifiers.

Electrostatic Secondary-Sphere Interactions That Facilitate Rapid and Selective Electrocatalytic CO2 Reduction in a Fe-Porphyrin-Based Metal-Organic Framework.

Metal–organic frameworks (MOFs) are promising platforms for heterogeneous tethering of molecular CO2 reduction electrocatalysts. Yet, to further understand electrocatalytic MOF systems, one also needs to consider their capability to fine‐tune the immediate chemical environment of the active site, and thus affect its overall catalytic operation. Here, we show that electrostatic secondary‐sphere functionalities enable substantial improvement of CO2‐to‐CO conversion activity and selectivity. In situ Raman analysis reveal that immobilization of pendent positively‐charged groups adjacent to MOF‐residing Fe‐porphyrin catalysts, stabilize weakly‐bound CO intermediates, allowing their rapid release as catalytic products. Also, by varying the electrolyte's ionic strength, systematic regulation of electrostatic field magnitude was achieved, resulting in essentially 100 % CO selectivity. Thus, this concept provides a sensitive molecular‐handle that adjust heterogeneous electrocatalysis on demand.

Primary- and secondary-sphere effects of amine substituent position on rhenium bipyridine electrocatalysts for CO2 reduction

It is well-established that electrocatalysts with biologically inspired moieties provide advantageous qualities for the efficient transformation of fossil fuel combustion products, such as carbon dioxide, into value-added products. Herein, we present a family of Re(bpy)(CO)3Cl electrocatalysts with pendant NH2 groups in the 4,4′-, 5,5′-, and 6,6′-positions of the bipyridine backbone with the objective of determining the effects of combined primary- and secondary-sphere interactions on the reduction of CO2 to CO. Cyclic voltammetry studies under CO2 indicate that the catalytic onset potential is more positive for 6,6′-NH2-Re, indicating that proximity of the available pendant protons to the metal center is beneficial during catalysis. Controlled potential electrolysis studies demonstrate that, similar to 6,6′-NH2-Re, 4,4′-NH2-Re displays a dependence of Faradaic efficiency (FE) on catalytic potential, reaching a maximum FECO of 91% at −2.40 V. This FE is greater than that observed for 6,6′-NH2-Re but occurs at a more negative potential. Density functional theory (DFT) calculations were performed to compare the HOMO-LUMO gap of these complexes, and the following trend of 4,4′-NH2-Re > 6,6′-NH2-Re > 5,5′-NH2-Re was determined. Mulliken electron population analysis indicates a greater degree of electron density on the metal center for 6,6′-NH2-Re compared to its related congeners, in agreement with the electrolysis studies which illustrate a more favorable CO2 reduction for 6,6′-NH2-Re. Ultimately, it is important that the various catalytic parameters are properly balanced to provide the greatest overall catalytic activity.

The Impact of Second Coordination Sphere Methionine-Aromatic Interactions in Copper Proteins.

The interplay between the primary and secondary coordination spheres in biological metal sites plays an essential role in controlling their properties. Some of the clearest examples of this are from copper sites in blue and purple copper proteins. Many such proteins contain methionine (Met) in the primary coordination sphere as a weakly bound ligand to Cu. While the effects of replacing the coordinated Met are understood, less so is the importance of its second-sphere interactions. In this combined informatics and experimental study, we first present a bioinformatics investigation of the second-sphere environments in biological Met-Cu motifs. The most common interaction is between the Met-CH3 and the π-face of a phenylalanine (Phe) (81% of surveyed structures), tyrosine (Tyr) (11%), and tryptophan (Trp) (8%). In most cases, the Met-CH3 also forms a contact with a π-face of one of a Cu-ligating histidine-imidazole. Such interactions are widely distributed in different Cu proteins. Second, to explore the impact of the second-sphere interactions of Met, a series of artificial Pseudomonas aeruginosa azurin proteins were produced where the native Phe15 was replaced with Tyr or Trp. The proteins were characterized using optical and magnetic resonance spectroscopies, X-ray diffraction, electrochemistry, and an investigation of the time-resolved electron-transfer kinetics of photosensitizer-modified proteins. The influence of the Cu-Met-Aro interaction on azurin's physical properties is subtle, and the hallmarks of the azurin blue copper site are maintained. In the Phe15Trp variant, the mutation to Phe15 induces changes in Cu properties that are comparable to replacement of the weak Met ligand. The broader impacts of these widely distributed interactions are discussed.

Second-Sphere Lattice Effects in Copper and Iron Zeolite Catalysis.

Transition-metal-exchanged zeolites perform remarkable chemical reactions from low-temperature methane to methanol oxidation to selective reduction of NOx pollutants. As with metalloenzymes, metallozeolites have impressive reactivities that are controlled in part by interactions outside the immediate coordination sphere. These second-sphere effects include activating a metal site through enforcing an "entatic" state, controlling binding and access to the metal site with pockets and channels, and directing radical rebound vs cage escape. This review explores these effects with emphasis placed on but not limited to the selective oxidation of methane to methanol with a focus on copper and iron active sites, although other transition-metal-ion zeolite reactions are also explored. While the actual active-site geometric and electronic structures are different in the copper and iron metallozeolites compared to the metalloenzymes, their second-sphere interactions with the lattice or the protein environments are found to have strong parallels that contribute to their high activity and selectivity.

Engineering lanmodulin's selectivity for actinides over lanthanides by controlling solvent coordination and second-sphere interactions.

Developing chelators that combine high affinity and selectivity for lanthanides and/or actinides is paramount for numerous industries, including rare earths mining, nuclear waste management, and cancer medicine. In particular, achieving selectivity between actinides and lanthanides is notoriously difficult. The protein lanmodulin (LanM) is one of Nature's most selective chelators for trivalent actinides and lanthanides. However, mechanistic understanding of LanM's affinity and selectivity for f-elements remains limited. In order to decipher, and possibly improve, the features of LanM's metal-binding sites that contribute to this actinide/lanthanide selectivity, we characterized five LanM variants, substituting the aspartate residue at the 9th position of each metal-binding site with asparagine, histidine, alanine, methionine, and selenomethionine. Spectroscopic measurements with lanthanides (Nd3+ and Eu3+) and actinides (243Am3+ and 248Cm3+) reveal that, contrary to the behavior of small chelator complexes, metal-coordinated water molecules enhance LanM's affinity for f-elements and pH-stability of its complexes. Furthermore, the results show that the native aspartate does not coordinate the metal directly but rather hydrogen bonds to coordinated solvent. By tuning this first-sphere/second-sphere interaction, the asparagine variant nearly doubles LanM's selectivity for actinides versus lanthanides. This study not only clarifies the essential role of coordinated solvent for LanM's physiological function and separation applications, but it also demonstrates that LanM's preference for actinides over lanthanides can be further improved. More broadly, it demonstrates how biomolecular scaffolds possess an expanded repertoire of tunable interactions compared to most small-molecule ligands – providing an avenue for high-performance LanM-based actinide/lanthanide separation methods and bio-engineered chelators optimized for specific medical isotopes.

Whither Second-Sphere Coordination?

Whither Second-Sphere Coordination?

The influence of secondary interactions on the [Ni(O2)]+ mediated aldehyde oxidation reactions

A rate enhancement of one to two orders of magnitude can be obtained in the aldehyde deformylation reactions by replacing the –N(CH3) groups of [NiIII(O2)(Me4[12]aneN4)]+ (Me4[12]aneN4 = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane) and [NiIII(O2)(Me4[13]aneN4)]+ (Me4[13]aneN4 = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclotridecane) complexes by –NH in [NiIII(O2)([12]aneN4)]+ (2; [12]aneN4 = 1,4,7,10-tetraazacyclododecane) and [NiIII(O2)([13]aneN4)]+ (4; [13]aneN4 = 1,4,7,10-tetraazacyclotridecane). Based on detailed spectroscopic, reaction-kinetics and theoretical investigations, the higher reactivities of 2 and 4 are attributed to the changes in the secondary-sphere interactions between the [NiIII(O2)]+ and [12]aneN4 or [13]aneN4 moieties, which open up an alternative electrophilic pathway for the aldehyde oxidation reaction. Identification of primary kinetic isotope effects on the reactivity and stability of 2 when the –NH groups of the [12]aneN4 ligand are deuterated may also suggest the presence of secondary interaction between the –NH groups of [12]aneN4 and [NiIII(O2)]+ moieties, although, such interactions are not obvious in the DFT calculated optimized structure at the employed level of theory.

Second-Sphere Interaction Promoted Turn-On Fluorescence for Selective Sensing of Organic Amines in a TbIII -based Macrocyclic Framework.

Guided by a second-sphere interaction strategy, we fabricated a Tb(III)-based metal-organic framework (MMCF-4) for turn-on sensing of methyl amine with ultra-low detection limit and high turn-on efficiency. MMCF-4 features lanthanide nodes shielded in a nonacoordinate geometry along with secondary coordination spheres that are densely populated with H-bond interacting sites. Nonradiative routes were inhibited by binding-induced rigidification of the ligand on the second coordination sphere, resulting in luminescence amplification. Such remote interacting mechanism involved in the turn-on sensing event was confirmed by single-crystal X-ray diffraction and molecular dynamic simulation studies. The design of both primary and secondary coordination spheres of Tb(III) enabled the first turn-on sensing of organic amines in aqueous conditions. Our work suggests a promising strategy for high-performance turn-on sensing for Ln-MOFs and luminous materials driven by other metal chromophores.

Mechanism of nickel-catalyzed direct carbonyl-Heck coupling reaction: the crucial role of second-sphere interactions

We present a detailed DFT mechanistic study on the first Ni-catalyzed direct carbonyl-Heck coupling of aryl triflates and aldehydes to afford ketones. The precatalyst Ni(COD)2 is activated with the phosphine (phos) ligand, followed by coordination of the substrate PhOTf, to form [Ni(phos)(PhOTf)] for intramolecular PhOTf to Ni(0) oxidative addition. The ensuing phenyl-Ni(ii) triflate complex substitutes benzaldehyde for triflate by an interchange mechanism, leaving the triflate anion in the second coordination sphere held by Coulomb attraction. The Ni(ii) complex cation undergoes benzaldehyde C[double bond, length as m-dash]O insertion into the Ni-Ph bond, followed by β-hydride elimination, to produce Ni(ii)-bound benzophenone, which is released by interchange with triflate. The resulting neutral Ni(ii) hydride complex leads to regeneration of the active catalyst following base-mediated deprotonation/reduction. The benzaldehyde C[double bond, length as m-dash]O insertion is the rate-determining step. The triflate anion, while remaining in the second sphere, engages in electrostatic interactions with the first sphere, thereby stabilizing the intermediate/transition state and enabling the desired reactivity. This is the first time that such second-sphere interaction and its impact on cross-coupling reactivity has been elucidated. The new insights gained from this study can help better understand and improve Heck-type reactions.

Homogeneous Catalysts Based on First-Row Transition-Metals for Electrochemical Water Oxidation.

Strategies that enable the renewable production of storable fuels (i. e. hydrogen or hydrocarbons) through electrocatalysis continue to generate interest in the scientific community. Of central importance to this pursuit is obtaining the requisite chemical (H+) and electronic (e−) inputs for fuel‐forming reduction reactions, which can be met sustainably by water oxidation catalysis. Further possibility exists to couple these redox transformations to renewable energy sources (i. e. solar), thus creating a carbon neutral solution for long‐term energy storage. Nature uses a Mn−Ca cluster for water oxidation catalysis via multiple proton‐coupled electron‐transfers (PCETs) with a photogenerated bias to perform this process with TOF 100∼300 s−1. Synthetic molecular catalysts that efficiently perform this conversion commonly utilize rare metals (e. g., Ru, Ir), whose low abundance are associated to higher costs and scalability limitations. Inspired by nature‘s use of 1st row transition metal (TM) complexes for water oxidation catalysts (WOCs), attempts to use these abundant metals have been intensively explored but met with limited success. The smaller atomic size of 1st row TM ions lowers its ability to accommodate the oxidative equivalents required in the 4e−/4H+ water oxidation catalysis process, unlike noble metal catalysts that perform single‐site electrocatalysis at lower overpotentials (η). Overcoming the limitations of 1st row TMs requires developing molecular catalysts that exploit biomimetic phenomena – multiple‐metal redox‐cooperativity, PCET and second‐sphere interactions – to lower the overpotential, preorganize substrates and maintain stability. Thus, the ultimate goal of developing efficient, robust and scalable WOCs remains a challenge. This Review provides a summary of previous research works highlighting 1st row TM‐based homogeneous WOCs, catalytic mechanisms, followed by strategies for catalytic activity improvements, before closing with a future outlook for this field.

Designing the Secondary Coordination Sphere in Small-Molecule Catalysis

AbstractThe application of secondary-sphere interactions in catalysis was inspired by the hierarchical arrangement of the microenvironment of metalloprotein active sites and has been adopted mainly in organometallic catalysis. The study of such interactions has enabled the deliberate orientation of reaction components, leading to control over reactivity and selectivity by design. Although not as common, such interaction can play a decisive role in organocatalysis. Herein, we present several examples of small-molecule organometallic- and organocatalysis, highlighting the advantages offered by carefully designing the secondary sphere.1 Introduction2 Secondary-Sphere Design in Organometallic Catalysis3 Secondary-Sphere Modification in Organocatalysis4 Using Statistical Analysis to Systematically Tune and Probe Secondary-Sphere Interactions5 Conclusion

Secondary Sphere Effects on Porous Polymeric Organocatalysts for CO2 Transformations: Subtle Modifications Resulting in Superior Performance.

Albeit harnessing secondary sphere interactions to exert control over the reaction outcomes has primarily been applied to enzymatic and organometallic catalysis, there are seldom any studies that introduce outer-sphere modifiers into organocatalysts. This is even less in the corresponding heterogeneous catalytic system. In this contribution, we experimentally and computationally investigate the role of secondary effects in the reactivity of bromide anions toward CO2 transformations. Six pyridinium cationic porous frameworks have been synthesized and fully characterized. Structure-activity relationships and kinetics show that the type and the location of the substituents on the cationic framework have a significant impact on the nucleophilic reactivity of their bromide counter anion. Specifically, the attachment of amine substituent to the ortho position relative to a pyridinium motif produces a remarkably efficient catalyst for CO2 transformation, by a factor of six times greater in comparison to the pristine pyridinium-based polymer. The hydrogen-bond-interaction-promoted reagent activation and enhanced delocalization ability of bromide counter anion are believed to be the key to driving the reaction toward CO2 utilization. These observations, therefore, champion the leverage of secondary interaction for optimizing the reactivity of organocatalysts.

Synthesis and Characterization of Cu(II) and Mixed-Valence Cu(I)Cu(II) Clusters Supported by Pyridylamide Ligands.

A group of copper complexes supported by polydentate pyridylamide ligands H2bpda and H2ppda were synthesized and characterized. The two Cu(II) dimers [CuII2(Hbpda)2(ClO4)2] (1) and [CuII2(ppda)2(DMF)2] (2) were constructed by using neutral ligands to react with Cu(II) salts. Although the dimers showed similar structural features, the second-sphere interactions affect the structures differently. With the application of Et3N, the tetranuclear cluster (HNEt3)[CuII4(bpda)2(μ3-OH)2(ClO4)(DMF)3](ClO4)2 (3) and hexanuclear cluster (HNEt3)2[CuII6(ppda)6(H2O)2(CH3OH)2](ClO4)2 (4) were prepared under similar reaction conditions. The symmetrical and unsymmetrical arrangement of the ligand donors in ligands H2bpda and H2ppda led to the dramatic conformation difference of the two Cu(II) complexes. As part of our effort to explore mixed-valence copper chemistry, the triple-decker pentanuclear cluster [CuII3CuI2(bpda)3(μ3-O)] (5) was prepared. XPS examination demonstrated the localized mixed-valence properties of complex 5. Magnetic studies of the clusters with EPR evidence showed either weak ferromagnetic or antiferromagnetic interactions among copper centers. Due to the trigonal-planar conformation of the trinuclear Cu(II) motif with the μ3-O center, complex 5 exhibits geometric spin frustration and engages in antisymmetric exchange interactions. DFT calculations were also performed to better interpret spectroscopic evidence and understand the electronic structures, especially the mixed-valence nature of complex 5.

Secondary-Sphere Chlorolanthanide(III) Complexes with a 1,3,5-Triazine-Based Ligand Supported by Anion-π, π-π, and Hydrogen-Bonding Interactions.

2,4,6-Dipicolylamine-functionalized 1,3,5-triazine (dpat) was isolated. When reacted with LaCl3, compound [(LaCl6)(H3dpat)][H2O]2 (1) formed, which crystallized in the monoclinic P21/n space group with parameters a = 11.47 Å, b = 19.22 Å, c = 20.98 Å, V = 4652.02 Å, and β = 90.53°. When reacted with NdCl3, the complex [NdCl3(H2O)4(H3dpat)][Cl]3(MeOH)2 (2) crystallized in the monoclinic P21/n space group with unit cell parameters a = 20.05 Å, b = 12.81 Å, c = 20.64 Å, V = 5004.40 Å, and β = 110.20°. In both cases, the dpat ligand forms a bowl-shaped cavity that partially envelops the LnIII-containing central unit, which is anionic in 1 and neutral in 2. The formation of these outer-sphere complexes is supported by secondary interactions, including π-π stacking, hydrogen bonding, and anion-π between the chlorolanthanide(III) fragment and the electron-deficient 1,3,5-triazine ring. Evidence of protonation of the pyridine rings in dpat was substantiated through the isolation of [H2dpat][Cl]2 (3). This compound crystallized in the monoclinic C2/c space group with parameters a = 11.93 Å, b = 20.22 Å, c = 15.28 Å, V = 3664.97 Å, and β = 94.35°. Four pyridine rings are pairwise protonated in 3. dpat showed a moderate ability to extract LaIII from an aqueous to an organic phase, indicating its potential, through judicious manipulation of secondary-sphere interactions, as the starting point for efficient extractants for LnIII ions.

Engineered Enzymes and Bioinspired Catalysts for Energy Conversion

Metalloenzymes play critical roles in the environment by catalyzing redox reactions in biogeochemical cycles. The elucidation of structure–function relationships in these biocatalysts has provided a foundation for the development of bioinspired catalysts for fuel production and small-molecule activation. In this Perspective, we highlight developments in engineered biomolecular and bioinspired catalysts for the reduction of H+, O2, and CO2 and for the oxidation of H2 and H2O. The roles of proton transfers and second-sphere interactions in particular are highlighted.