Steric Research Articles

Kinetic Studies of CO2 Insertion into Metal-Element σ-Bonds.

ConspectusDespite the plethora of metal catalyzed reactions for CO2 utilization that have been developed in academic laboratories, practical systems remain elusive. The understanding of the elementary steps in catalysis is a proven method to improve catalytic performance. In many catalytic cycles for CO2 utilization, the insertion of CO2 into a metal-element σ-bond, such as hydrides, alkyls, amides, or hydroxides, is a crucial step. However, despite the many demonstrations of CO2 insertion, there are a paucity of kinetic studies, and information about the reaction mechanism has been predominantly elucidated from computational investigations. In this Account, kinetic studies on CO2 insertion into late transition metal-element σ-bonds performed by my group are summarized, along with their implications for catalysis.A common pathway for CO2 insertion into a metal hydride involves a two-step mechanism. The first step is nucleophilic attack on CO2 by the hydride to generate an H-bound formate, followed by rearrangement to form an O-bound formate product. Kinetic studies on systems in which both the first and second steps are proposed to be rate-determining, known as inner-sphere and outer-sphere processes, respectively, show that insertion rates increase as (i) the ligand trans to the hydride becomes a stronger donor, (ii) the ancillary ligand becomes more electron-donating, and (iii) the Dimroth-Reichardt parameter of the solvent increases. However, the magnitude of these effects is generally smaller for inner-sphere processes because there is less buildup of charge in the key transition state. For similar reasons, the presence of Lewis acids only increases the rate of outer-sphere processes. These results suggest it may be possible to experimentally differentiate between inner- and outer-sphere processes.The insertion of CO2 into a metal-alkyl bond results in the formation of a C-C bond, which is important for the generation of fuels from CO2. For square planar Group 10 complexes, the presence of a strong donor ligand trans to the alkyl group is critical for kinetically promoting insertion. Further, the nucleophilicity of the alkyl ligand directly impacts the rate of CO2 insertion via an SE2 mechanism, as does the steric bulk of the complex, and the reaction solvent. In contrast to the relatively slow rates of insertion observed for metal alkyls, CO2 insertion is rapid for metal hydroxides and amides. Although kinetics trends could be determined for hydroxides, reactions with amides are too fast for quantitative studies.Overall, the rates of insertion correlate with the nucleophilicity of the element in the metal-element σ-bond, so amide > hydroxide > hydride > alkyl. Due to the related pathways for insertion, similar trends in ligand and solvent effects are observed for insertion into different metal-element σ-bonds. Thus, the same strategies can be used to control the rates of insertion across systems. Differences in the magnitude of solvent and ligand effects are caused by variation in the amount of charge build-up on the metal in the rate-determining transition state. Likely, given that CO2 is related to organic molecules such as aldehydes, ketones, and amides, the results described in this Account are general to a wider range of substrates.

De- and Rearomatisation of Pyridine in Silylene Chemistry.

Traditional methods relying on metal-ligand cooperation for activating pyridine bonds in de- and rearomatisation are being challenged by the abundant metal-free element species as alternatives. Here, we investigated the de/re-aromatisation of pyridine facilitated by pyridylamino-functionalised silylene reactions with ketones and ketene. The reactivity outcome is highly dependent on the substituents on the ketones. By carefully tuning the steric demand of the ketone, each intermediate of the reaction sequence could be isolated. At room temperature, benzophenone and acetophenone substrates led to dearomatisation of the pyridine moiety, with the case of acetophenone showing an intermediate silaoxirane preceding dearomatisation. However, when subjected to acetone or diphenylketene, only silaoxiranes were formed without dearomatisation of the pyridine moiety. Notably, only benzophenone-derived dearomatised species demonstrated rearomatisation upon heating. Furthermore, the reduced steric bulk of the ketene facilitated further ring expansion with another equivalent of the substrate, forming sila-1,3-dioxolanes. Both steric hindrance and aromatic groups collectively influence the dearomatisation of pyridine in pyridylaminosilylene reactions.

Cone Angles Quantify and Predict the Affinity and Reactivity of Anion Complexes between Trifluoroborates and Rigid Macrocycles

AbstractSteric manipulation is a known concept in molecular recognition but there is currently no linear free energy relationship correlating sterics to the stability of receptor‐anion complexes nor to the reactivity of the bound anion. By analogy to Tolman cone angles in cation coordination chemistry, we explore how to define and correlate cone angles of organo‐trifluoroborates (R−BF3−) to the affinities observed for cyanostar‐anion binding. We extend the analogy to a rare investigation of the anion's reactivity and how it changes upon binding. The substituent on the anion is used to define the cone angle, θ. A series of 10 anions were studied including versions with ethynyl, ethylene, and ethyl substituents to tune steric bulk across the sp, sp2 and sp3 hybridized α‐carbons bearing 0, 1 and 2 hydrogen atoms. A linear relationship between affinity and cone angle is observed for anions bearing substituents larger than the −BF3− headgroup. This correlation predicted affinities of two new anions to within ±5 %. We explored how complexation affects the reactivity of fluoride exchange. The yield of fluoride transfer from R−BF3− to Lewis acid triphenylborane is correlated with cone angle. We predict that other rigid macrocycles, like commercially available bambusuril, could follow these trends.

Borane-Catalyzed Enantioselective α-Alkylation of Unactivated 2-Alkylbenzoxazoles with Electron-Deficient Olefins.

Chiral borane-catalyzed reactions have recently emerged as a powerful tool for the enantioselective production of chiral scaffolds. In this study, we demonstrated for the first time that a chiral bisborane catalyst can be used for the α-functionalization of 2-alkylazaarenes; specifically, we accomplished unprecedented highly enantioselective α-alkylation of unactivated 2-alkylbenzoxazoles with electron-deficient olefins. The strong Lewis acidity and the steric bulk of the bisborane catalyst were essential to the observed reactivity and selectivity.

In-Situ Investigation of Surface Modifiers Dithiocarbamates on Au Electrodes for Electrochemical CO2 Reduction

Molecular functionalization of metal electrodes via self-assembled monolayers (SAMs) can introduce synthetically tunable properties to metal surfaces and has exhibited great potential in electrocatalysis. Alkanethiols are commonly used organic ligands because of their strong affinity to Au but they are prone to desorption at negative potentials. Alternatively, dithiocarbamates (DTC) show superior electrochemical stability. In this study, a series of DTCs, differing in hydrophobicity, size, and steric bulk, were synthesized to prepare SAM-functionalized Au electrodes. The properties of the resulting surfaces (e.g. wettability, surface coverage, and reductive stability) were investigated by analytical and electrochemical techniques. Particularly, in-situ approaches such as surface-enhanced infrared absorption spectroscopy (SEIRAS) are employed to characterize the molecularly modified interface. The novel catalyst platforms were explored for electrochemical CO2 reduction.

Low-Coordinate Iron Hydride Chemistry at an N,N,C-Heteroscorpionate Platform.

Locally high-spin iron hydrides are proposed to play a critical role as intermediates in iron-molybdenum cofactor (FeMoco)-catalyzed N2 fixation. Inspired by these biological systems, we report herein our initial investigations into low-coordinate iron hydride chemistry supported by our N,N,C-heteroscorpionate ligands. Those ligands with smaller steric profiles are unable to completely suppress the formation of a binuclear [Fe(μ2-H)]2 complex; however, the incorporation of more substantial steric bulk allows for the isolation of a rare example of a terminal, high-spin (S = 2) Fe2+ hydride. Fourier transform infrared spectroscopy suggests an unusually weak Fe-H bond in the latter molecule. Mössbauer spectroscopies, coupled with density functional theory calculations, highlights the substantial influence of the terminal hydride ligand on 57Fe isomer shift.

Air processed, high open‐circuit voltage indoor organic photovoltaic cells based on side chain modified N‐annulated perylene diimides

AbstractTo achieve high‐performance indoor organic photovoltaics (OPVs), it is important to match the photoactive layer optical absorption with the light‐source emission. This can be accomplished by developing organic photoactive materials that can efficiently absorb visible light and thus minimize energy losses. While indoor OPVs have achieved efficiencies above 33% under low light intensities, the power output is limited by low open circuit voltages (VOC), often well below 1 V. In this study, we present a series of visible‐light absorbing (energy gap >1.90 eV) non‐fullerene acceptors (NFAs) based on perylene diimide dimers, which have been systematically modified with side chains of varying polarity and steric bulk (trimethyl benzyl, ethyl adamantane, trialkoxyl phenyl, and oligo ethylene glycol). Our results show that the incorporation of sterically bulky side chains such as ethyl adamantane and trimethyl benzyl, blended with the common widegap polymer PTQ10, provides photoactive layers with absorption greater than 2.0 eV, and consequently, VOCs higher than 1.2 V are achieved under AM 1.5 G illumination. Importantly, we found that the NFA with ethyl adamantane based side chains (tPDI2N‐ethyl adamantane, compound 4) exhibited the best performance, with minimized energy loss. As a result, devices using PTQ10:tPDI2N‐ethyl adamantane photoactive layers demonstrated excellent indoor efficiencies of over 16% and 18 μW cm−2 power output under a 2700 K LED lamp at 300 lux, and showed better repeatability compared to other systems. The PTQ10:tPDI2N‐ethyl adamantane based devices maintained a high VOC (>1.0 V) across a wide range of indoor lighting conditions, including 2700 K and 6500 K LED lamps. Overall, this work provides a sidechain engineering method to create NFAs for efficient indoor OPV devices.

Reactivity and Steric Parameters from 2D to 3D Bulky Pyridines: Increasing Steric Demand at Nitrogen with Chiral Azatriptycenes

AbstractSterically hindered pyridines embedded in a three‐dimensional triptycene framework have been synthesized, and their resolution by chiral HPLC enabled access to unprecedented enantiopure pyridines exceeding the known steric limits. The design principles for new axially chiral pyridine derivatives are then described. To rationalize their associations with Lewis acids and transition metals, a comprehensive determination of the steric and electronic parameters for this new class of pyridines was performed. This led to the general parameterization of the steric parameters (percent buried volume %VBur, Tolman cone angle θ, and He8_steric descriptor) for a large set of two‐ and three‐dimensional pyridine derivatives. These parameters are shown to describe quantitatively their interactions with carbon‐ and boron‐centered Lewis acids and were used to predict the ΔG° of association with the prototypical B(C6F5)3 Lewis acid widely used in frustrated Lewis pair catalysis. This first parameterization of pyridine sterics is a fundamental basis for the future development of predictive reactivity models and for guiding new applications of bulky and chiral pyridines in organocatalysis, frustrated Lewis pairs, and transition‐metal catalysis.

Reactivity and Steric Parameters from 2D to 3D Bulky Pyridines: Increasing Steric Demand at Nitrogen with Chiral Azatriptycenes.

Sterically hindered pyridines embedded in a three-dimensional triptycene framework have been synthesized, and their resolution by chiral HPLC enabled access to unprecedented enantiopure pyridines exceeding the known steric limits. The design principles for new axially chiral pyridine derivatives are then described. To rationalize their associations with Lewis acids and transition metals, a comprehensive determination of the steric and electronic parameters for this new class of pyridines was performed. This led to the general parameterization of the steric parameters (percent buried volume %VBur, Tolman cone angle θ, and He8_steric descriptor) for a large set of two- and three-dimensional pyridine derivatives. These parameters are shown to describe quantitatively their interactions with carbon- and boron-centered Lewis acids and were used to predict the ΔG° of association with the prototypical B(C6F5)3 Lewis acid widely used in frustrated Lewis pair catalysis. This first parameterization of pyridine sterics is a fundamental basis for the future development of predictive reactivity models and for guiding new applications of bulky and chiral pyridines in organocatalysis, frustrated Lewis pairs, and transition-metal catalysis.

Interactions with DNA Models of the Oxaliplatin Analog (cis-1,3-DACH)PtCl2.

It is generally accepted that adjacent guanine residues in DNA are the primary target for platinum antitumor drugs and that differences in the conformations of the Pt-DNA adducts can play a role in their antitumor activity. In this study, we investigated the effect of the carrier ligand cis-1,3-diaminocyclohexane (cis-1,3-DACH) upon formation, stability, and stereochemistry of the (cis-1,3-DACH)PtG2 and (cis-1,3-DACH)Pt(d(GpG)) adducts (G = 9-EthlyGuanine, guanosine, 5'- and 3'-guanosine monophosphate; d(GpG) = deoxyguanosil(3'-5')deoxyguanosine). A peculiar feature of the cis-1,3-DACH carrier ligand is the steric bulk of the diamine, which is asymmetric with respect to the Pt-coordination plane. The (cis-1,3-DACH)Pt(5'GMP)2 and (cis-1,3-DACH)Pt(3'GMP)2 adducts show preference for the ΛHT and ∆HT conformations, respectively (HT stands for Head-to-Tail). Moreover, the increased intensity of the circular dichroism signals in the cis-1,3-DACH derivatives with respect to the analogous cis-(NH3)2 species could be a consequence of the greater bite angle of the cis-1,3-DACH carrier ligand with respect to cis-(NH3)2. Finally, the (cis-1,3-DACH)Pt(d(GpG)) adduct is present in two isomeric forms, each one giving a pair of H8 resonances linked by a NOE cross peak. The two isomers were formed in comparable amounts and had a dominance of the HH conformer but with some contribution of the ΔHT conformer which is related to the HH conformer by having the 3'-G base flipped with respect to the 5'-G residue.

Intramolecular Nucleophilic Vinylic Substitution (SNV) by Carbon Nucleophiles: Conformationally Directed Formation of Dienes from N,N'-Diallyl Ureas.

Nucleophilic vinylic substitution (SNV) by carbon nucleophiles allows the formation of vinylic C-C bonds without transition metal catalysts. In this paper, we show that tethering two alkenes together through a urea linkage can lead to the formation of a diene by an intramolecular SNV reaction. The starting materials are fully substituted N,N'-diallyl ureas; the reaction proceeds in the presence of base, and entails a cascade of deprotonations, reprotonations, and an SNV reaction of an allylic carbanion on a rare electrophile: a vinylic urea. As a result, two allylic substituents couple to form a diene, despite the fact that neither is activated towards electrophilic attack. The reaction is tolerant of significant steric bulk, and exhibits regioselectivity with unsymmetrical diallyl ureas: β-substituted allyl groups invariably behave as nucleophiles, while electrophilic behavior may be enforced by the use of an E-vinylic urea substituent that cannot be deprotonated under the reaction conditions.

Transpersulfidation or H2S Release? Understanding the Landscape of Persulfide Chemical Biology.

Persulfides (RSSH) are biologically important reactive sulfur species that are endogenously produced, protect key cysteine residues from irreversible oxidation, and are important intermediates during different enzymatic processes. Although persulfides are stronger nucleophiles than their thiol counterparts, persulfides can also act as electrophiles in their neutral, protonated form in specific environments. Moreover, persulfides are electrophilic at both sulfur atoms, and the reaction with a thiolate can lead to either H2S release with disulfide formation or alternatively result in transpersulfidation. Despite the broad acceptance of these reaction pathways, the specific properties that control whether persulfides react through the H2S-releasing or transpersulfidation pathway remain elusive. Herein, we use a combined computational and experimental approach to directly investigate the reactivity between persulfides and thiols to answer these questions. Using density functional theory (DFT) calculations, we demonstrate that increasing steric bulk or electron withdrawal near the persulfide can shunt persulfide reactivity through the transpersulfidation pathway. Building from these insights, we use a synthetic persulfide donor and an N-iodoacetyl l-tyrosine methyl ester (TME-IAM) trapping agent to experimentally monitor and measure transpersulfidation from a bulky penicillamine-based persulfide to a cysteine-based thiol, which, to the best of our knowledge, is the first direct observation of transpersulfidation between low-molecular-weight species. Taken together, these combined approaches highlight how the properties of persulfides are directly impacted by local environments, which has significant impacts in understanding the complex chemical biology of these reactive species.

Syntheses and Conformations of a Trinuclear Gold(I) System Based on a Triethinyl‐trisilacyclohexane Scaffold

AbstractTrisilacyclohexanes and bissilylmethanes with acetylene units attached to silicon sites have been converted into tri‐ and di‐nuclear gold(I)phosphane complexes and characterized by NMR spectroscopy and X‐ray diffraction. The bissilylmethane‐based gold complexes were used as a test system to work out the synthetic routes before transferring them to the trisilacyclohexane scaffolds, because the latter are more difficult to access. The occurrence of aurophilic interactions (short Au ⋅ ⋅ ⋅ Au contacts) depends on the steric bulk of the phosphorus‐bonded alkyl and aryl groups. DFT studies show that dispersion effects play an important role in the ability to form intramolecular Au ⋅ ⋅ ⋅ Au interactions. QTAIM analyses show that a subtle change of the steric bulk of the phosphane groups alters the relative strength of the dispersion and aurophilic interactions. The combination of DFT studies and X‐ray diffraction experiments shows that the conformation of the trisilacyclohexane backbone is also phase dependent.

Coinage Metal Complexes of a Sterically Encumbered Anionic Pyridylborate.

Sterically loaded, anionic pyridine has been synthesized and utilized successfully in the stabilization of a isoleptic series of coinage metal complexes. The treatment of [4-(Ph3B)-2,6-Trip2Py]K (Trip=2,4,6-iPr3C6H2) with CuBr(PPh3), AgCl(PPh3) or AuCl(PPh3) (Py=pyridine) afforded the corresponding [4-(Ph3B)-2,6-Trip2Py]M(PPh3) (M=Au, Ag, Cu) complexes, via salt metathesis, as isolable, crystalline solids. Notably, these reactions avoid the facile single electron transfer chemistry reported with the less bulky ligand systems. The X-ray structures revealed that they are two-coordinate metal adducts. The M-N and M-P bond distances are longest in the silver and shortest in the copper adduct among the three group 11 family members. Computational analysis revealed an interesting stability dependence on steric bulk of the anionic pyridine (i. e., pyridyl borate) ligand. A comparison of structures and bonding of [4-(Ph3B)-2,6-Trip2Py]Au(PPh3) to pyridine and m-terphenyl complexes, {[2,6-Trip2Py]Au(PPh3)}[SbF6] and [2,6-Trip2Ph]Au(PPh3) are also provided. The Au(I) isocyanide complex, [4-(Ph3B)-2,6-Trip2Py]Au(CNBut) has been stabilized using the same anionic pyridylborate illustrating that it can support other gold-ligand moieties as well.

Influence of the steric bulk of a trityl group in the formation of molecular metallosilicates

The molecular silanol (Ph3CO)(iPrO)2Si(OH) was designed to evaluate the degree of steric bulk the trityl moiety imposes on the Si–OH group. The reactivity of the silanol was evaluated by the formation of three metallosilicates with lithium, aluminum, and gallium, and their molecular structures and the degree of association were determined. Hirshfeld atom refinement or DFT calculation, and QTAIM analysis of the electron density in all compounds were used to analyze the bonding situation in the metallosilicate moieties and determine the strength of the intermolecular hydrogen bonds formed by the silanol. Finally, ring-opening polymerization of ε-caprolactone was used as another criterion for the evaluation of the steric bulk imposed by the trityl group.

Chiral 1-D coordination polymer chains featuring 1,1′-binaphthyl

Four 1-D chain coordination polymers containing bent 1,1′-binaphthyl ligands were synthesised with NiII, CuII and AgI. The use of (R)-4,4′-(2,2′-diethoxy-[1,1′-binaphthalene]-6,6′)dipyridine as a ligand yielded isostructural 1-D looping chains with NiII and CuII, whereas the use of AgI yielded both linear and helical 1-D chains. Changing the dipyridyl coordination groups to dicarboxylates in (S)-6,6′-dicarboxyl-2,2′-diethoxy-1,1′-binaphthalene yielded a 1-D looping chain with a CuII paddlewheel motif. The AgI 1-D chain features two crystallographically distinct 1-D chain morphologies with a triple helix and linear strips. The packing arrangement of the 1-D chains differs because of the intermolecular interactions present, with the steric bulk of the ethoxy substituent on the 1,1′-binaphthyl enabling the formation of large void spaces.

New half-sandwich ruthenium(II) complexes of chelating (SS) organochalcogen ligands and their application as transfer hydrogenation catalysts

Room temperature reactions of [(η6-arene)Ru(μ-Cl)Cl]2 (arene = p-cymene) with three new bidentate (SS) organochalcogen ligands, 2a–c (2a: 1,1’-ethylenebis(3-ethyl-imidazole-2-thione), 2b: 1,1’-ethylenebis(3-propyl-imidazole-2-thione), 2c: 1,1’-methylenebis(3-ethyl-imidazole-2-thione)), and in situ anionic exchange with KPF6 afforded the corresponding new 18-electron half-sandwich [(η6-arene)RuLCl]PF6 complexes 3a–c (3a: L = 2a, 3b: L = 2b, 3c: L = 2c). The Ru(II) complexes and the organochalcogen ligands were fully characterized by spectroscopic and analytical techniques. Solid state single crystal X-ray diffraction analysis of 3a–c displayed the Ru(II) center in the expected piano stool geometry. The catalytic activities of the half-sandwich ruthenium complexes toward the transfer hydrogenation of ketones to their corresponding alcohols were investigated using 2-propanol as a hydrogen source and solvent. All three Ru(II) complexes exhibited excellent catalytic activity for the transfer hydrogenation of ketones in the order 3b > 3a > 3c at an appreciably low catalyst loading of 0.5 mol% under a minimal alkaline condition of 10 mol% KOH. The catalytic activities of the complexes are influenced by the length of the alkyl spacer and the steric bulk of the N-substituents on the chelating organochalcogen ligand framework.

Second-Generation Chiral Amino Acid Derivatives Afford High Stereoselectivity and Stability in Aqueous RNA Acylation.

Activated acyl species have proven versatile in the esterification of 2'-OH groups in RNA, enabling structure mapping, caging, profiling, and labeling of the biopolymer. Nearly all reagents developed for this reaction have been achiral; however, a recent study reported that simple chiral amino acid acylimidazole derivatives could yield diastereoselective reactions at RNA 2'-OH in water, enabling up to 4:1 selectivity in screening. Here, we investigated the effect of steric bulk on the stereoselectivity of RNA reaction and on the stability of adducts with a library of 36 chiral acylimidazole scaffolds with increasing steric demand. The results document the highest stereoselectivity yet achieved in RNA acylation reactions, with as high as >99:1 diastereoselectivity at >70% conversion. Also notably, the bulky adducts were found to have markedly improved stability on RNA.

A General Method for Elemental Sulfur Promoted Synthesis of Ortho‐Substituted Pyrrolo[1,2‐a]quinoxalin‐4‐yl Anilines

AbstractSynthesis of heteroaryl ortho‐substituted anilines is hitherto challenging. Herein we report scope and limitation of method for annulation of 1‐(2‐nitroaryl)pyrroles and derivatives of 2‐aminobenzyl alcohol to afford ortho‐substituted pyrrolo[1,2‐a]quinoxalin‐4‐yl anilines. Reaction conditions contained elemental sulfur as promoter, while were tolerant of a wide range of aryl and heteroaryl amines. Our method would offer a feasible tactic to yield anilines steric bulk with ortho heterocyclic substituents.

Modulating Excited State Properties and Ligand Ejection Kinetics in Ruthenium Polypyridyl Complexes Designed to Mimic Photochemotherapeutics.

Ruthenium(II) polypyridyl complexes have gained significant interest as photochemotherapeutics (PCTs) due to their synthetic viability, strong light absorption, well understood excited state properties, and high phototoxicity indexes. Herein, we report the synthesis, characterization, electrochemical, spectrochemical, and preliminary cytotoxicity analyses of three series of ruthenium(II) polypyridyl complexes designed to mimic PCTs. The three series have the general structure of [Ru(bpy)2(N-N)]2+ (Series 1), [Ru(bpy)(dmb)(N-N)]2+ (Series 2), and [Ru(dmb)2(N-N)]2+ (Series 3, where N-N is a bidentate polypyridyl ligand, bpy = 2,2'-bipyridine, and dmb = 6,6'-dimethyl-2,2'-bipyridine). In the three series, the N-N ligand was systematically modified to incorporate increased conjugation and/or electronegative heteroatoms to increase dπ-π* backbonding, red-shifting the lowest energy metal-to-ligand charge transfer (MLCT) absorptions from λmax = 454 to λmax = 580 nm, nearing the therapeutic window for PCTs (600-1100 nm). In addition, steric bulk was systematically introduced through the series, distorting the Ru(II) octahedra, making the dissociative 3dd* state thermally accessible at room and body temperatures. This resulted in a 4 orders of magnitude increase in photoinduced ligand ejection kinetics, and demonstrates the ability to modulate both the MLCT* and dd* manifolds in the complexes, which is critical in PCT drug design. Preliminary cell viability assays suggest that the increased steric bulk to lower the 3dd* states may interfere with the cytotoxicity mechanism, limiting photoinitiated toxicity of the complexes. This work demonstrates the importance of understanding both the MLCT* and dd* manifolds and how they impact the ability of a complex to act as a PCT agent.