Proposed Reaction Intermediates Research Articles

Elucidation of the Pyridine Ring-Opening Mechanism of 2,2'-Bipyridine or 1,10-Phenanthroline Ligands at Re(I) Carbonyl Complexes.

The cleavage of the C-N bonds of aromatic heterocycles, such as pyridines or quinolines, is a crucial step in the hydrodenitrogenation (HDN) industrial processes of fuels in order to minimize the emission of nitrogen oxides into the atmosphere. Due to the harsh conditions under which these reactions take place (high temperature and H2 pressure), the mechanism by which they occur is only partially understood, and any study at the molecular level that reveals new mechanistic possibilities in this area is of great interest. Herein, we unravel the pyridine ring-opening mechanism of 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen) ligands coordinated to the cis-{Re(CO)2(N-RIm)(PMe3)} (N-RIm= N-alkylimidazole) fragment under mild conditions. Computational calculations show that deprotonation of the pyridine ring, once dearomatized, is crucial to induce ring contraction, triggering extrusion of the nitrogen atom from the ring and cleavage of the C-N bond. It is noteworthy that different products (regioisomers) are obtained depending on whether the ligand used is bipy or phen due to the additional rigidity and stability conferred by the central ring of the phen ligand, an issue also addressed and clarified computationally. Strong support for the proposed mechanism is provided by the characterization and isolation, including three single-crystal X-ray diffraction structures, of several of the proposed reaction intermediates.

Kavain Hydroxylation in Kava Metabolism: Computational Analysis

Kava, a non-alcoholic beverage derived from the Piper methysticum plant, commonly also known as Kava, has a prominent role in the cultures of Oceania due to its calming and soothing effects. These psychoactive properties have sparked interest beyond Oceania and in the scientific community, who see potential for medicinal applications. However, alongside these beneficial effects, consumption of Kava has been linked to potential hepatotoxicity, raising safety concerns. Understanding the cause of this hepatotoxicity requires a detailed exploration of Kava's metabolic processes, specifically those involving kavain, its primary constituent. Recent studies have found the hydroxylation of kavain to 12-hydroxykavain as a key step in Kava's metabolic pathway. Yet, the precise mechanism of this conversion and the hydroxylation intermediates involved remain poorly understood. To address this knowledge gap, our study employed Spartan, a computational chemistry software, to model the hydroxylation process. We analyzed the stability and chemical properties of the proposed reaction intermediates, providing a detailed view of this critical phase of metabolism. Our analysis reveals that three of the five proposed intermediates appear stable, suggesting they may play significant roles in the hydroxylation process. This finding also enabled us to narrow down the possible reaction pathways of hydroxylation. Having a better understanding of the key step of Kava metabolism could guide the development of safer, more effective Kava-based products, balancing the therapeutic potential of Kava with a reduced risk profile.

Triel tris(aminoaryl)aluminum, gallium, and indium complexes and their homocoupling reactions mediated by NiBr2

Here, we present the synthesis, spectroscopic characterization, structural analysis, and studies on the bonding situation of group 13 tris(o-aminoaryl) complexes, [M(C6H4(o-NMe2))3] (1–3) and [M(C10H6(o-NMe2))3] (4–6) where M = Al, Ga, In. X-ray and DFT structural parameters, in conjunction with the inspection of the molecular electrostatic potential (MEP) of related triaryl, MAr3, models where Ar = C6H4, C10H6, suggest for 1–6 the presence of two partially polar covalent intramolecular M–N triel bonds. Interestingly, indium complexes 3 and 6 bind a third nitrogen atom with a Van der Waals type interaction. Stoichiometrical reactions of 1–3 with NiBr2 at 25 °C afforded the homocoupling product bi-o-dimethylaminophenyl (7) in up to 73 % isolated yield with 1 and 3 as the nucleophile. While 4–6 performed poorly under the same reaction conditions or at 100 °C providing either traces or at most 13 % of bi-o-dimethylaminonaphtyl (8) with 4 according to GC–MS. Hypothetical DFT bimetallic species [BrNi(μ-Br)M{C6H4(o-NMe2)}3] and [Ni(Br)2M{C10H6(o-NMe2}3] where M = Al (9, 12), Ga (10, 13), In (11, 14) are proposed reaction intermediates implied in the transmetalation/reductive elimination process that affords diaromatic amines 7 and 8.

Mechanistic Insights into Superoxide Dismutation Driven by Dinuclear Manganese Complexes: The Role of the Mn2-Core

The dinuclear Mn2(II,II)L2-core (HL = 2-{[[di(2-pyridyl)methyl](methyl)amino]-methyl}phenol) has been recently reported to be the most active dual superoxide dismutase (SOD) and catalase (CAT) functional analogue, enabling cascade detoxification of the superoxide radical anion. Here, we investigated the mechanism of catalytic O2•– decomposition by two stereoisomers with the Mn2(II,II)L2-core, Mn2L2Ac and Mn2L2, in order to (i) precisely determine the catalytic SOD activity of the complexes, (ii) characterize the key intermediates involved in the dismutation process, and (iii) discriminate between single- and di-Mn center catalysis in relation to the configuration of the Mn2-core. The conclusions drawn from low-temperature mass spectrometry, stopped-flow kinetics, cyclic voltammetry, water exchange 17O nuclear magnetic resonance (NMR), and electron paramagnetic resonance (EPR) analyses were supported by the structural characterization and quantum chemical analysis of the proposed reaction intermediates. This study allows us to determine kcat for Mn2L2Ac and Mn2L2 (4.6 × 107 and 2.2 × 107 M–1 s–1, respectively, in 3-(N-morpholino)propanesulfonic acid (MOPS) at pH = 7.4) and detect the key intermediates involved in the catalytic cycle driven by these Mn2-SOD mimics, highlighting the formation of a side-on η2–Mn2(III,II)–peroxo, as an initial intermediate. The effects of the Mn2(II,II)-core configuration on the SOD activity were discussed.

Exploiting Coordination Behavior of 7-Azaindole for Mechanistic Investigation of Chan-Lam Coupling and Application to 7-Azaindole Based Pharmacophores.

Multiple spectroscopic techniques, along with single-crystal X-ray analysis, have been used to reveal the detailed structural and electronic information on reaction intermediates of a new copper(II)-DBU catalytic system for the N-arylation of 7-Azaindole. The reaction mixture of Chan-Lam cross-coupling yields two dimeric copper(II)-7-azaindole complexes, including one attached with DBU, prior to adding arylboronic acid and are confirmed structurally and spectroscopically. A suitable mechanism has been proposed using the dimeric copper(II) complex as a catalyst for the coupling reactions. The role of DBU as a base and also as an auxiliary ligand in the course of the reaction has been established. The transmetalated monomeric aryl-copper(II) species generated from the dimeric unit is oxidized by another equivalent of copper(II) to yield an aryl-copper(III) intermediate for facile N-arylation, which has been authenticated with UV-vis spectroscopy. The regeneration of the copper(II)-catalyst by aerial oxidation of colorless copper(I) species (generated via reductive elimination and disproportionation step) is confirmed by mass and absorption spectroscopy. Detailed DFT and TD-DFT calculations help to rationalize the proposed reaction intermediates and their corresponding electronic transitions. Moreover, the confirmation of copper(I)-7-azaindole intermediate via HRMS reaffirmed the involvement of Cu(II)/Cu(III)/Cu(I) species in the Chan-Lam type of coupling. A medicinally-important 7-azaindole-based SHP2 inhibitor has been synthesized via sequential arylation.

A Molecular Analogue of the C−H Activation Intermediate of the Silica‐Supported Ga(III) Single‐Site Propane Dehydrogenation Catalyst: Structure and XANES Signature

AbstractPropane dehydrogenation is an important field of research due to an increasing world‐wide demand of propene while classical production routes through naphtha cracking are in decline. In that context, silica‐supported Ga(III) sites, synthesized from surface organometallic chemistry principles, show high selectivity and stability in the propane dehydrogenation reaction. This performance is in significant contrast to the reported fast deactivation and lower selectivity of most Ga2O3 and CrO3 based materials. The Ga‐catalyzed propane dehydrogenation reaction is proposed to proceed through the formation of Ga alkyl intermediates for which it would be desirable to have detailed structural and spectroscopic information. Here, we prepare a consistent series of Ga(III) molecular complexes with varying numbers of alkyl and siloxide ligands; they are characterized by single crystal X‐Ray diffraction and X‐Ray Absorption Near Edge Structure analysis, which is known to be highly sensitive to the Ga coordination environment. We report in particular the structure and the spectroscopic signatures of [Ga(iPr)(OSi(OtBu)3)2(HOSi(OtBu)3)], a molecular mimic of the key proposed reaction intermediates in the Ga‐catalyzed PDH reaction.

Ethylene oligomerization studies utilizing nickel complexes bearing pyridine-imine ligands

Two pyridine-imine ligands (6E,7E)-N1,N4-bis((pyridin-2-yl)methylene)benzene-1,4-diamine (L1) and (6E,13E)-N1,N4-bis(1-(pyridin-2-yl)ethylidene)benzene-1,4-diamine (L2) were synthesized in good yields. Reactions with L1 and L2 with Ni salts afforded nickel complexes NiCl2{(6E,7E)-N1,N4-bis((pyridin-2-yl)methylene)benzene-1,4-diamine}NiCl2 (C1) and NiCl2{(6E,13E)-N1,N4-bis(1-(pyridin-2-yl)ethylidene)benzene-1,4-diamine}NiCl2 (C2). The compounds were characterized through NMR (1H NMR and 13C NMR), IR, UV–Vis, MS and elemental analysis. Upon activation with a co-catalyst, C1 and C2 both displayed good catalytic activity (0.63 × 104–16.66 × 104 g/mol Ni h and 0.11 × 105–23.70 × 105 g/mol Ni h, respectively) in ethylene oligomerization experiments, the oligomer products followed the classic Schulz-Flory distribution with mostly 1-C4= oligomers. The catalytic performance was obviously affected by the reaction parameters including reaction temperature, reaction pressure, Al/Ni molar ratio, reaction time and co-catalyst type. The experimental data suggested that C1 and C2 generally had quite different catalytic performance under the same reaction conditions indicating the catalyst structure had a significant influence on the catalytic performance. The density functional theory (DFT) calculation was utilized to optimize the geometry structure for exploring the relationship between structure and catalytic properties. Combined with a proposed mechanism, reaction intermediates and frontier molecular orbitals were simulated for further studying the intermediates structure and energy variation in ethylene oligomerization process.

Theoretical Study of the Electrocatalytic Reduction of Oxygen by Metallocorroles

Metallocorroles are transition metal complexes showing great promise as oxygen reduction reaction catalysts. The performance of metallocorrole catalysts is highly sensitive to the nature of the transition metal employed, although currently this dependence remains elusive. In the current work, we present a first principles density functional theory (DFT) investigation of the oxygen reduction reaction mechanism in acidic media using several first-row transition metal corroles. We show that the identity of the metal center, M, determines the relative formation free energies of the reaction intermediates, and thus the potential-determining step in the four-electron reduction process directly to water. For M═Mn, Fe, and Co, the hydroperoxyl intermediate is a thermodynamic maximum along the reaction path, whereas for Ni and Cu, the formation of the hydroperoxyl intermediate is a thermodynamic trap, with the following oxo intermediate being highly unstable. The formation of the oxo intermediate was carefully investigated using several flavors of DFT. The calculations suggest that in the oxo intermediate, the spin density on the oxygen atom increases from M═Mn to M═Cu, indicating a purely metal oxygen double bond for M═Mn, a single metal oxygen bond with an unpaired electron on the oxygen atom for M═Ni and Cu, whereas for M═Fe and Co, the spin density on the oxygen atom has intermediate values. When plotting the experimentally observed onset potentials as a function of the computed O2 adsorption free energies, a volcano-like plot is observed, indicating that for the best catalyst, [Co(tpfcBr8)], a negative binding free energy is observed. A good correlation between the computed limiting and the experimental onset potentials indicates that the computationally proposed reaction intermediates are viable states along the reaction coordinate. The current work is expected to be of importance for the future design of efficient metallocorrole-based catalysts.

An Accessible Method for DFT Calculation of 11B NMR Shifts of Organoboron Compounds.

The study of boron-mediated reactions in organic synthesis and reactions of organoboron compounds is greatly facilitated by the use of 11B NMR. However, the identification and characterization of reaction intermediates in often complex systems is far from trivial, as 11B NMR does not provide any detailed structural information. Greater insight into the structures present in such systems can be obtained by using DFT chemical shift calculations to support or exclude proposed reaction intermediates. In this article, we report a rapid and accessible approach to the calculation of 11B NMR shifts that is applicable to a wide range of organoboron compounds.

Synthesis and Reactivity of Model Intermediates Proposed for the Pd-Catalyzed Remote C–H Functionalization of N-(2-Haloaryl)acrylamides

We have studied the possible reaction pathways operating in the Pd-catalyzed remote C–H functionalization of N-(2-haloaryl)acrylamides from an organometallic approach. We have isolated and characterized several proposed reaction intermediates, such as σ-alkyl-Pd complexes and spiro C,C-palladacycles, and evaluated the role of the base and the auxiliary ligands coordinated to Pd in the remote C–H activation process. In addition, the reactivity of these intermediates toward different unsaturated species such as benzyne, alkynes, and isocyanides has been studied in order to gain further insight into the reaction mechanism leading to functionalized spiro-oxoindoles.

Substrate-Coated Illumination Droplet Spray Ionization: Real-Time Monitoring of Photocatalytic Reactions.

Real-time monitoring of photocatalytic reactions facilitates the elucidation of the mechanisms of the reactions. However, suitable tools for real-time monitoring are lacking. Herein, a novel method based on droplet spray ionization named substrate-coated illumination droplet spray ionization (SCI-DSI) for direct analysis of photocatalytic reaction solution is reported. SCI-DSI addresses many of the analytical limitations of electrospray ionization (ESI) for analysis of photocatalytic-reaction intermediates, and has potential for both in situ analysis and real-time monitoring of photocatalytic reactions. In SCI-DSI-mass spectrometry (MS), a photocatalytic reaction occurs by loading sample solutions onto the substrate-coated cover slip and by applying UV light above the modified slip; one corner of this slip adjacent to the inlet of a mass spectrometer is the high-electric-field location for launching a charged-droplet spray. After both testing and optimizing the performance of SCI-DSI, the value of this method for in situ analysis and real-time monitoring of photocatalytic reactions was demonstrated by the removal of cyclophosphamide (CP) in TiO2/UV. Reaction times ranged from seconds to minutes, and the proposed reaction intermediates were captured and identified by tandem mass spectrometry. Moreover, the free hydroxyl radical (·OH) was identified as the main radicals for CP removal. These results show that SCI-DSI is suitable for in situ analysis and real-time monitoring of CP removal under TiO2-based photocatalytic reactions. SCI-DSI is also a potential tool for in situ analysis and real-time assessment of the roles of radicals during CP removal under TiO2-based photocatalytic reactions.Graphical Abstract.

Effect of Pore and Cage Size on the Formation of Aromatic Intermediates During the Methanol-to-Olefins Reaction

Six eight-membered-ring (8MR), microporous materials are synthesized and evaluated as catalysts for the methanol-to-olefins (MTO) reaction. The molecular sieves SSZ-13, SAPO-34, SAPO-39, MCM-35, ERS-7 and RUB-37 are investigated since they have 8MR access to the crystal interior but have differences in pore structure and cage size. The polymethylbenzene species that are the proposed reaction intermediates of the MTO reaction should only be able to form in materials with intra-molecular sieve void spaces of sufficient size to accommodate them. Thus, it is hypothesized that 8MR materials without adequately large pores or cages will be inactive for the MTO reaction. SSZ-13 and SAPO-34 (both with CHA framework topology) have interconnected 3-dimensional pore-and-cage systems sufficiently large for formation of the proposed reaction intermediates, while the other 8MR materials have intra-molecular sieve void spaces that are too small to allow formation of these species. The molecular sieves are tested as MTO catalysts at 400 °C, and only the molecular sieves with the CHA topology show MTO activity. Post-reaction analysis of the organic content of each solid material is accomplished by HF acid digestion with subsequent 1H NMR analysis of the extracted hydrocarbon products to confirm the presence of aromatics in the 8MR materials with sufficiently large cages (those with CHA topology), and absence with materials that have smaller void spaces. These data provide further support for the necessity of polymethylbenzene species in the hydrocarbon pool for MTO activity.

Infrared matrix isolation and theoretical studies of reactions of ozone with bicyclic alkenes: α-pinene, norbornene, and norbornadiene.

The reactions of ozone with three bicyclic alkenes, α-pinene, norbornene, and norbornadiene, were studied by low-temperature (14 K), argon matrix isolation infrared spectroscopy including (18)O isotope-labeling studies. Theoretical calculations of some of the proposed reaction intermediates and products were carried out using the Gaussian 09 suite of programs, applying density functional theory (DFT), the B3LYP functional, and the 6-311G++(d,2p) basis set. In the α-pinene/ozone system, the thermal reaction between α-pinene and ozone was too slow to observe under the twin-jet or merged-jet deposition conditions of these experiments. However, red light (λ ≥ 600 nm) irradiation of the argon matrixes containing α-pinene and ozone caused new infrared peaks to appear that could be readily assigned to reaction products of α-pinene with O((3)P) resulting from ozone photolysis: α-pinene oxide (with an epoxide ring) and two isomeric ketones. Norbornene and norbornadiene were both found to react with ozone in the gas phase during twin-jet or merged-jet deposition of these mixtures with argon. New peaks observed in the infrared spectra were assigned to the primary ozonides, Criegee intermediates, and secondary ozonides of norbornene and norbornadiene, indicating that the bulk of these reactions proceeded via the "classic" Criegee mechanism for ozonolysis of alkenes. Calculated infrared frequencies and molecular energies support these conclusions. Ultraviolet irradiation of these mixtures resulted in complete decomposition of the early intermediates and the formation of acids, aldehydes, alcohols, carbon dioxide, and carbon monoxide. In any case, no evidence for "unusual" chemistry, prompted by the bicyclic nature of the reactants, was observed.

Trapping of an Intermediate in the Reaction Catalyzed by Flavin-Dependent Thymidylate Synthase

Thymidylate is a DNA nucleotide that is essential to all organisms and is synthesized by the enzyme thymidylate synthase (TSase). Several human pathogens rely on an alternative flavin-dependent thymidylate synthase (FDTS), which differs from the human TSase both in structure and molecular mechanism. It has recently been shown that FDTS catalysis does not rely on an enzymatic nucleophile and that the proposed reaction intermediates are not covalently bound to the enzyme during catalysis, an important distinction from the human TSase. Here we report the chemical trapping, isolation, and identification of a derivative of such an intermediate in the FDTS-catalyzed reaction. The chemically modified reaction intermediate is consistent with currently proposed FDTS mechanisms that do not involve an enzymatic nucleophile, and it has never been observed during any other TSase reaction. These findings establish the timing of the methylene transfer during FDTS catalysis. The presented methodology provides an important experimental tool for further studies of FDTS, which may assist efforts directed toward the rational design of inhibitors as leads for future antibiotics.

ChemInform Abstract: Photocatalytic Ring Opening of α‐Epoxyketones in Cyclopentanone.

In our recent studies, we have investigated the photocatalytic ring opening of various α-epoxyketones of interest by TPT as photocatalyst in the presence of methanol [7], cyclohexanone [8], acetic acid [9], and acetone [10]. The aims of these studies were to elucidate the effect of the additional substituent on the parent molecule and the nucleophilicity and also the steric hindranceof the solventmoleculeon the rate and diastereoselectivity of the reaction. Among the nucleophiles studied, only the reaction in the presenceof cyclohexanone resulted in the formation of a single diastereomer. The reason is possibly the steric hindrance of cyclohexanone compared to other nucleophiles in the attack on the proposed reaction intermediates from theless hinderedside [8].In continuationof thesestudies, we have investigated the photocatalytic ring opening of certain α-epoxyketones by TPT in cyclopentanone to elucidate the effect of the nature and the steric hindrance of the nucleophile on the diastereoselectivity of the reaction.

ChemInform Abstract: An Organocatalytic Domino Thia‐Michael/Aldol Condensation Reaction: Highly Enantioselective Synthesis of Functionalized Dihydrothiophenes.

An organocatalytic domino thia-Michael/ aldol condensation reaction of α, β-unsaturated aldehydes with 1, 4-dithiane-2,5-diol catalyzed by chiral diphenylprolinol TMS ether has been developed, which provides a new practical and direct route to chiral dihydrothiophenes with high yields (up to 90%) and excellent enantioselectivities (up to>99% ee). The catalytic mechanism of the domino reaction was further confirmed through the APCI-MS detection of proposed reaction intermediates.

Spin‐Trapping Evidence for the Formation of Alkyl, Alkoxyl, and Alkylperoxyl Radicals in the Reactions of Dialkylzincs with Oxygen

The reactions of dialkylzincs (Me(2)Zn, Et(2)Zn, and nBu(2)Zn) with oxygen have been investigated by EPR spectroscopy using spin-trapping techniques. The use of 5-diethoxyphosphoryl-5-methyl-1-pyrrroline N-oxide (DEPMPO) as a spin-trap has allowed the involvement of alkyl, alkylperoxyl, and alkoxyl radicals in this process to be probed for the first time. The relative ratio of the corresponding spin-adducts depends strongly on the nature of the R group, which controls the C-Zn bond dissociation enthalpy, and on the experimental conditions (excess of spin-trap compared with R(2)Zn and vice versa). The results have demonstrated that Et(2)Zn and, to a lesser extent, nBu(2)Zn are much better traps for oxygen-centered species than Me(2)Zn. When the dialkylzincs were used in excess with respect to the spin-trap, the concentration of the oxygen-centered radical adducts of DEPMPO was much lower for Et(2)Zn and nBu(2)Zn than for Me(2)Zn. A detailed reaction mechanism is discussed and C-Zn, O-Zn, and O-O bond dissociation enthalpies for the proposed reaction intermediates were calculated at the UB3LYP/6-311++G(3df,3pd)//UB3LYP/6-31G(d,p) level of theory to support the rationale.

High-resolution crystal structures of Streptococcus pneumoniae nicotinamidase with trapped intermediates provide insights into the catalytic mechanism and inhibition by aldehydes .

Nicotinamidases are salvage enzymes that convert nicotinamide to nicotinic acid. These enzymes are essential for the recycling of nicotinamide into NAD(+) in most prokaryotes and most single-cell and multicellular eukaryotes, but not in mammals. The significance of these enzymes for nicotinamide salvage and for NAD(+) homeostasis has stimulated interest in nicotinamidases as possible antibiotic targets. Nicotinamidases are also regulators of intracellular nicotinamide concentrations, thereby regulating signaling of downstream NAD(+)-consuming enzymes, such as the NAD(+)-dependent deacetylases (sirtuins). Here, we report several high-resolution crystal structures of the nicotinamidase from Streptococcus pneumoniae (SpNic) in unliganded and ligand-bound forms. The structure of the C136S mutant in complex with nicotinamide provides details about substrate binding, while a trapped nicotinoyl thioester in a complex with SpNic reveals the structure of the proposed thioester reaction intermediate. Examination of the active site of SpNic reveals several important features, including a metal ion that coordinates the substrate and the catalytically relevant water molecule and an oxyanion hole that both orients the substrate and offsets the negative charge that builds up during catalysis. Structures of this enzyme with bound nicotinaldehyde inhibitors elucidate the mechanism of inhibition and provide further details about the catalytic mechanism. In addition, we provide a biochemical analysis of the identity and role of the metal ion that orients the ligand in the active site and activates the water molecule responsible for hydrolysis of the substrate. These data provide structural evidence of several proposed reaction intermediates and allow for a more complete understanding of the catalytic mechanism of this enzyme.

An Organocatalytic Domino Thia‐Michael/Aldol Condensation Reaction: Highly Enantioselective Synthesis of Functionalized Dihydrothiophenes

AbstractAn organocatalytic domino thia‐Michael/aldol condensation reaction of α, β‐unsaturated aldehydes with 1, 4‐dithiane‐2,5‐diol catalyzed by chiral diphenylprolinol TMS ether has been developed, which provides a new practical and direct route to chiral dihydrothiophenes with high yields (up to 90%) and excellent enantioselectivities (up to>99%ee). The catalytic mechanism of the domino reaction was further confirmed through the APCI‐MS detection of proposed reaction intermediates.

Reaction intermediates of methanol synthesis and the water–gas-shift reaction on the ZnO(0001) surface

The polar Zn-ZnO(0001) surface is involved in the catalysis of methanol synthesis and the water–gas-shift reaction. We use density functional theory calculations to explore the favorable binding geometries and energies of adsorption of several molecular species relevant to these reactions, namely carbon monoxide (CO), carbon dioxide (CO 2), water (H 2O) and methanol (CH 3OH). We also consider several proposed reaction intermediates, including hydroxymethyl (CH 2OH), methoxyl (CH 3), formaldehyde (CH 2O), methyl (CH 3), methylene (CH 2), formic acid (HCOOH), formate (HCOO), formyl (HCO), hydroxyl (OH), oxygen (O) and hydrogen (H). For each, we identify the preferred binding geometry at a coverage of 1/4 monolayers (ML), and report calculated vibrational frequencies that could aid in the identification of these species in experiment. We further explore the effects on the binding energy when the adsorbate coverage is lowered to 1/9 and 1/16 ML.