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Mo-nitrogenase hydrogenates N2 to NH3. This report continues from the previous paper [I. Dance, Dalton Trans., 2024, 53, 14193–14211] that described how the active site FeMo-co of the enzyme is uniquely able to capture and activate N2, forming a key intermediate with Fe-bound HNNH. Density functional simulations with a 485+ atom model of the active site and its surroundings are used to describe here the further reactions of this HNNH intermediate. The first step is hydrogenation to form HNNH2 bridging Fe2 and Fe6. Then a single-step reaction breaks the N–N bond, generating an Fe2–NH–Fe6 bridge and forming NH3 bound to Fe6. Then NH3 dissociates from Fe6. Reaction potential energies and kinetic barriers for all steps are reported for the most favourable electronic states of the system. The steps that follow the Fe2–NH–Fe6 intermediate, forming and dissociating the second NH3, and regenerating the resting state of the enzyme, are outlined. These results provide an interpretation of the recent steady-state kinetics data and analysis by Harris et al., [Biochemistry, 2022, 61, 2131–2137] who found a slow step after the formation of the HNNH intermediate. The calculated potential energy barriers for the HNNH2 → NH + NH3 reaction (30–36 kcal mol−1) are larger than the potential energy barriers for the N2 → HNNH reaction (19–29 kcal mol−1). I propose that the post-HNNH slow step identified kinetically is the key HNNH2 → NH + NH3 reaction described here. This step and the N2-capture step are the most difficult in the conversion of N2 to 2NH3. The steps in the complete mechanism still to be computationally detailed are relatively straightforward. [ABSTRACT FROM AUTHOR]

Mo-nitrogenase hydrogenates N2 to NH3. This report continues from the previous paper [I. Dance, Dalton Trans., 2024, 53, 14193–14211] that described how the active site FeMo-co of the enzyme is uniquely able to capture and activate N2, forming a key intermediate with Fe-bound HNNH. Density functional simulations with a 485+ atom model of the active site and its surroundings are used to describe here the further reactions of this HNNH intermediate. The first step is hydrogenation to form HNNH2 bridging Fe2 and Fe6. Then a single-step reaction breaks the N–N bond, generating an Fe2–NH–Fe6 bridge and forming NH3 bound to Fe6. Then NH3 dissociates from Fe6. Reaction potential energies and kinetic barriers for all steps are reported for the most favourable electronic states of the system. The steps that follow the Fe2–NH–Fe6 intermediate, forming and dissociating the second NH3, and regenerating the resting state of the enzyme, are outlined. These results provide an interpretation of the recent steady-state kinetics data and analysis by Harris et al., [Biochemistry, 2022, 61, 2131–2137] who found a slow step after the formation of the HNNH intermediate. The calculated potential energy barriers for the HNNH2 → NH + NH3 reaction (30–36 kcal mol−1) are larger than the potential energy barriers for the N2 → HNNH reaction (19–29 kcal mol−1). I propose that the post-HNNH slow step identified kinetically is the key HNNH2 → NH + NH3 reaction described here. This step and the N2-capture step are the most difficult in the conversion of N2 to 2NH3. The steps in the complete mechanism still to be computationally detailed are relatively straightforward. [ABSTRACT FROM AUTHOR]

Dinitrogen is inherently inert. This report describes detailed density functional calculations (with a 485+ atom model) of mechanistic steps by which the enzyme nitrogenase activates unreactive N2 at the intact active site FeMo-co, to form a key intermediate with bound HNNH. This mechanism does not bind N2 first and then add H atoms, but rather captures N2 ('N2-ready') that diffuses in through the substrate channel and enters a strategic gallery of H atom donors in the reaction zone, between Fe2 and Fe6. This occurs at the E4 stage of the complete mechanism. Exploration of possible reactions of N2 in this space leads to the conclusion that the first reaction step is transfer of H on Fe7 to one end of N2-ready, soon followed by Fe--N bond formation, and then a second H transfer from bridging S2BH to the other N. Two H--N bonds and one or two N--Fe bonds are formed, in some cases with a single transition state. The vari- able positions and orientations of N2-ready lead to various reaction trajectories and products. The favourable products resulting from this capture, judged by the criteria of reaction energies, reaction barriers, and mechanistic competence for further hydrogenation reactions in the nitrogenase cycle, have Fe2-- NH--NH bonding. The trajectory of one N2 capture reaction is described in detail, and calculations that separate the H atom component and the 'heavy atom' components of the classical activation energy are described, in the context of possible H atom tunneling in the activation of N2-ready. I present arguments for the activation of N2 by the pathway of concerted hydrogenation and binding of N2-ready, alternative to the commonly assumed pathway of binding N2 first, with subsequent hydrogenation. The active site of nitrogenase is well primed for the thermodynamic and kinetic advantages of N2 capture. [ABSTRACT FROM AUTHOR]

In converting N2 to NH3 the enzyme nitrogenase utilises 8 electrons and 8 protons in the complete catalytic cycle. The source of the electrons is an Fe4S4 reductase protein (Fe-protein) which temporarily docks with the MoFe-protein that contains the catalytic active cofactor, FeMo-co, and an electron transfer cluster called the P cluster. The overall mechanism involves 8 repetitions of a cycle in which reduced Fe-protein docks with the MoFe-protein, one electron transfers to the P-cluster, and then to FeMo-co, followed by dissociation of the two proteins and re-reduction of the Fe-protein. Protons are supplied serially to FeMo-co by a Grotthuss proton translocation mechanism from the protein surface along a conserved chain of water molecules (a proton wire) that terminates near S atoms of the FeMo-co cluster [CFe7S9Mo(homocitrate)] where the multiple steps of the chemical conversions are effected. It is assumed that the chemical mechanisms use proton-coupled electron-transfer (PCET) and that H atoms (e− + H+) are involved in each of the hydrogenation steps. However there is neither evidence for, or mechanism proposed, for this coupling. Here I report calculations of cluster charge distribution upon electron addition, revealing that the added negative charge is on the S atoms of FeMo-co, which thereby become more basic, and able to trigger proton transfer from H3O+ waiting at the near end of the proton wire. This mechanism is supported by calculations of the dynamics of the proton transfer step, in which the barrier is reduced by ca. 3.5 kcal mol−1 and the product stabilised by ca. 7 kcal mol−1 upon electron addition. H tunneling is probable in this step. In nitrogenase it is electron transfer that triggers proton transfer. [ABSTRACT FROM AUTHOR]

The binding of N2 to FeMo-co, the catalytic site of the enzyme nitrogenase, is central to the conversion to NH3, but also has a separate role in promoting the N2-dependent HD reaction (D2 + 2H+ + 2e− → 2HD). The protein surrounding FeMo-co contains a clear channel for ingress of N2, directly towards the exo-coordination position of Fe2, a position which is outside the catalytic reaction domain. This led to the hypothesis [I. Dance, Dalton Trans., 2022, 51, 12717] of 'promotional' N2 bound at exo-Fe2, and a second 'reducible' N2 bound in the reaction domain, specifically the endo-coordination position of Fe2 or Fe6. The range of possibilities for the binding of reducible N2 in the presence of bound promotional N2 is described here, using density functional simulations with a 486 atom model of the active site and surrounding protein. The pathway for ingress of the second N2 through protein, past the first N2 at exo-Fe2, and tumbling into the binding domain between Fe2 and Fe6, is described. The calculations explore 24 structures involving 6 different forms of hydrogenated FeMo-co, including structures with S2BH unhooked from Fe2 but tethered to Fe6. The calculations use the most probable electronic states. End-on (η1) binding of N2 at the endo position of either Fe2 or Fe6 is almost invariably exothermic, with binding potential energies ranging up to −18 kcal mol−1. Many structures have binding energies in the range −6 to −14 kcal mol−1. The relevant entropic penalty for N2 binding from a diffusible position within the protein is estimated to be 4 kcal mol−1, and so the binding free energies for reducible N2 are suitably negative. N2 binding at endo-Fe2 is stronger than at endo-Fe6 in three of the six structure categories. In many cases the reaction domain containing reducible N2 is expanded. These results inform computational simulation of the subsequent steps in which surrounding H atoms transfer to reducible N2. [ABSTRACT FROM AUTHOR]

The active site of the nitrogen fixing enzyme nitrogenase is an Fe7MoS9C cluster, and investigations of the enigmatic chemical mechanism of the enzyme have focussed on a pair of Fe atoms, Fe2 and Fe6, and the S2B atom that bridges them. There are three proposals for the status of the Fe2–S2B–Fe6 bridge during the catalytic cycle: one that it remains intact, another that it is completely labile and absent during catalysis, and a third that S2B is hemilabile, unhooking one of its bonds to Fe2 or Fe6. This report examines the tethered unhooking of S2B and factors that affect it, using DFT calculations of 50 geometric/electronic possibilities with a 485 atom model including all relevant parts of surrounding protein. The outcomes are: (a) unhooking the S2B–Fe2 bond is feasible and favourable, but alternative unhooking of the S2B–Fe6 bond is unlikely for steric reasons, (b) energy differences between hooked and unhooked isomers are generally <10 kcal mol−1, usually with unhooked more stable, (c) ligation at the exo-Fe6 position inhibits unhooking, (d) unhooking of hydrogenated S2B is more favourable than that of bare S2B, (e) hydrogen bonding from the NεH function of His195 to S2B occurs in hooked and unhooked forms, and possibly stabilises unhooking, (f) unhooking is reversible with kinetic barriers ranging 10–13 kcal mol−1. The conclusion is that energetically accessible reversible unhooking of S2B or S2BH, as an intrinsic property of FeMo-co, needs to be considered in the formulation of mechanisms for the reactions of nitrogenase. [ABSTRACT FROM AUTHOR]

The enzyme nitrogenase converts N2 to NH3 with stoichiometry N2 + 8H+ + 8e− → 2NH3 + H2. The mechanism is chemically complex with multiple steps that must be consistent with much accumulated experimental information, including exchange of H2 and N2 and the N2-dependent hydrogenation of D2 to HD. Previous investigations have developed a collection of working hypotheses that guide ongoing density functional investigations of mechanistic steps and sequences. These include (i) hypotheses about the serial provision of protons and their conversion to H atoms bonded to S and Fe atoms of the FeMo-co catalytic site, (ii) the migration of H atoms over the surface of FeMo-co, (iii) the roles of His195, (iv) identification of three protein channels, one for the ingress of N2, a separate pathway for the passage of exogenous H2 (D2) and product H2 (HD), and a hydrophilic pathway for egress of product NH3. Two additional working hypotheses are described in this paper. N2 passing along the N2 channel approaches and binds end-on to the exo coordination position of Fe2, with favourable energetics when FeMo-co is pre-hydrogenated. This exo-Fe2–N2 is apparently not reduced but has a promotional role by expanding the reaction zone. A second N2 can enter via the N2 ingress channel and bind at the endo-Fe6 position, where it is surrounded by H atom donors suitable for the N2 → NH3 conversion. It is proposed that this endo-Fe6 position is also the binding site for H2 (generated or exogenous), accounting for the competitive inhibition of N2 reduction by H2. The HD reaction occurs at the endo-Fe6 site, promoted by N2 at the exo-Fe2 site. The second hypothesis concerns the most stable electronic states of FeMo-co with ligands bound at Fe2 and Fe6, and provides a protocol for management of electronic states in mechanism calculations. [ABSTRACT FROM AUTHOR]

The chemical reactions occurring at the Fe7MoS9C(homocitrate) cluster, FeMo-co, the active site of the enzyme nitrogenase (N2 → NH3), are enigmatic. Experimental information collected over a long period reveals aspects of the roles of N2 and H2, each with more than one type of reactivity. This paper reports investigations of the binding of H2 and N2 at intact FeMo-co, using density functional simulations of a large 486 atom relevant portion of the protein, resulting in 27 new structures containing H2 and/or N2 bound at the exo and endo coordination sites of the participating Fe atoms, Fe2 and Fe6. Binding energies and transition states for association/dissociation are determined, and trajectories for the approach, binding and separation of H2/N2 are described, including diffusion of these small molecules through proximal protein. Influences of surrounding amino acids are identified. FeMo-co deforms geometrically when binding H2 or N2, and a procedure for calculating the energy cost involved, the adaptation energy, is introduced here. Adaptation energies, which range from 7 to 36 kcal mol−1 for the reported structures, are influenced by the protonation state of the His195 side chain. Seven N2 structures and three H2 structures have negative binding free energies, which include the estimated entropy penalties for binding of N2, H2 from proximal protein. These favoured structures have N2 bound end-on at exo-Fe2, exo-Fe6 and endo-Fe2 positions of FeMo-co, and H2 bound at the endo-Fe2 position. Various postulated structures with N2 bridging Fe2 and Fe6 revert to end-on-N2 at endo positions. The structures are also assessed via the calculated potential energy barriers for association and dissociation. Barriers to the binding of H2 range from 1 to 20 kcal mol−1 and barriers to dissociation of H2 range from 3 to 18 kcal mol−1. Barriers to the binding of N2, in either side-on or end-on mode, range from 2 to 18 kcal mol−1, while dissociation of bound N2 encounters barriers of 3 to 8 kcal mol−1 for side-on bonding and 7 to 18 kcal mol−1 for end-on bonding. These results allow formulation of mechanisms for the H2/N2 exchange reaction, and three feasible mechanisms for associative exchange and three for dissociative exchange are identified. Consistent electronic structures and potential energy surfaces are maintained throughout. Changes in the spin populations of Fe2 and Fe6 connected with cluster deformation and with metal–ligand bond formation are identified. [ABSTRACT FROM AUTHOR]

The active site of the enzyme nitrogenase (N2→ NH3) is a Fe7MoS9C cluster that contains three doubly-bridging μ-S atoms around a central belt. A vanadium nitrogenase variant has a slightly different cluster, containing two μ-S atoms. Recent crystal structures have revealed substitution of one μ-S (S2B, bridging Fe2 and Fe6), by CO in Mo-nitrogenase and an uncertain light atom in V-nitrogenase. These systems retained catalytic activity, and were able to recover the lost μ-S atom. Electron density attributed to the dissociated S is displaced by 7 Å in the crystal structure of the non-standard V-protein. The hypothesis arising from these observations is that the chemical mechanism of nitrogenase involves reversible dissociation of S2B, leaving Fe2 and Fe6 seriously under-coordinated and reactive in trapping N2 and binding reaction intermediates. Accumulated experimental evidence points to the Fe2–S2B–Fe6 domain as the centre of catalytic hydrogenation of N2. Using DFT simulations of a large model (＞488 atoms) containing all relevant surrounding protein residues, I have investigated the chemical steps that could allow dissociation of S2B. The participation of H atoms is crucial, as is involvement of the nearby side chain of His195 that can function as proton donor to S2B and hydrogen-bonding supporter of displaced S2B. A significant result is that after ingress and binding of N2 at Fe2 the breaking of the Fe2–S2B bond can be strongly exergonic with negligible kinetic barrier. Subsequent extension of the Fe6–S2B bond and dissociation as H2S (or SH−) is endergonic by 20–25 kcal mol−1, partly because the separating H2S is restricted by surrounding amino-acids. I present a number of reaction sequences and energy landscapes, and derive thirteen chemical principles relevant to the postulated S-dissociation mechanism. A key conclusion is that unhooking of S2BH or S2BH2 from Fe2 is favourable, likely, and propitious for subsequent H transfer to bound N2 or reaction intermediates. The space between Fe2 and Fe6 supports two bridging ligands, and another H atom on Fe6 can move without kinetic barrier to occupy the bridging position vacated by S2B. [ABSTRACT FROM AUTHOR]

The active site of the N2 fixing enzyme nitrogenase is a C-centred Fe7MoS cluster (FeMo-co) containing a trigonal prism of six Fe atoms connected by a central belt of three doubly-bridging S atoms. The trigonal faces of the prism are capped via triply-bridging S atoms to Fe1 at one end and Mo at the other end. One of the central belt atoms, S2B, considered to be important in the chemical mechanism of the enzyme, has been shown by Spatzal, Rees et al. to undergo substitution by CO, and also substitution by Se in the presence of SeCN−, under turnover conditions. Further, when turning over under C2H2 or N2/CO there is migration of Se to the other two belt bridging positions. These reactions are extraordinary, and unprecedented in metal chalcogenide cluster chemistry. Using density functional simulations, mechanisms for all of these reactions have been developed, involving the small molecules SCO, SeCO, C2H2S, C2H2Se, SeCN−, SCN− functioning as carriers of S and Se atoms. The possibility that the S2B bridge position is vacant is discounted, because the barrier to formation of a bridge-void intermediate with two contiguous three-coordinate Fe atoms is too large. A bridging ligand is retained throughout the proposed mechanisms. Intermediates with Fe–C(O)–S/Se–Fe cycles and with SCO/SeCO C-bound to Fe are predicted. The energetics of the reaction trajectories show them to be feasible and easily reversible, consistent with experiment. Alternative mechanisms involving intramolecular differential rotatory rearrangements of the cluster to scramble the Se bridges are also examined, and shown to be very unlikely. The implications of these new facets of the reactivity of the FeMo-co cluster are discussed: it is considered that they are unlikely to be part of the mechanism of the physiological reactions of nitrogenase. [ABSTRACT FROM AUTHOR]

Nitrogenase contains a well defined and conserved chain of water molecules leading to the FeMo cofactor (FeMo-co, an [Fe7MoCS9] cluster with bidentate chelation of Mo by homocitrate) that is the active site where N2 and other substrates are sequentially hydrogenated using multiple protons and electrons. The function of this chain is proposed to be a proton wire, serially translocating protons to triply-bridging S3B of FeMo-co, where, concomitant with electron transfer to FeMo-co, an H atom is generated on S3B. Density functional simulations of this proton translocation mechanism are reported here, using a large 269-atom model that includes all residues hydrogen bonded to and surrounding the water chain, and likely to influence proton transfer: three carboxylate O atoms of obligatory homocitrate are essential. The mechanism involves the standard two components of the Grotthuss mechanism, namely H atom slides that shift H3O+ from one water site to the next, and HOH molecular rotations that convert backward (posterior) OH bonds in the water chain to forward (anterior) OH bonds. The topography of the potential energy surface for each of these steps has been mapped. H atom slides pass through very short (ca. 2.5 Å) O–H–O hydrogen bonds, while HOH rotations involve the breaking of O–H…O hydrogen bonds, and the occurrence of long (up to 3.6 Å) separations between contiguous water molecules. Both steps involve low potential energy barriers, ＜7 kcal mol−1. During operation of the Grotthuss mechanism in nitrogenase there are substantial displacements of water molecules along the chain, occurring as ripples. These characteristics of the ‘Grotthuss two-step’, coupled with a buffering ability of two carboxylate O atoms of homocitrate, and combined with density functional characterisation of the final proton slide from the ultimate water molecule to S3B (including electron addition), have been choreographed into a complete mechanism for serial hydrogenation of FeMo-co. The largest potential barrier is estimated to be 14 kcal mol−1. These results are discussed in the context of reactivity data for nitrogenase, and the occurrence of a comparable water chain in cytochrome-c oxidase. Further investigation of the low-frequency conformational dynamics of the nitrogenase proteins, coupling proton transfer with other events in the nitrogenase cycle, is briefly canvassed. [ABSTRACT FROM AUTHOR]

The elimination of H2 from an M(H)2 component of a coordination complex is often described as reductive elimination, in which the H atoms are regarded as hydride ions, and the product complex after elimination is regarded as reduced by two electrons. The concept is Mn+2(H−)2→ Mn + H2 (with oxidative addition as its reverse). This interpretation contravenes Pauling's electroneutrality principle, and a number of researchers of metal–hydrogen systems have warned against literal acceptance of the formalism. A mechanism suggested by others for the chemical catalysis occurring at the Fe7MoS9C active site cluster of nitrogenase has invoked reductive elimination of H2 from Fe as a central premise. I report here calculations of atom partial charges for the relevant nitrogenase steps, as well as atom partial charges for some well-studied Fe complexes that model the nitrogenase chemistry. Fe-coordinated H atoms are ＜20% hydridic, and during the H2 elimination process the charge on Fe is essentially invariant. The argument for literal reductive elimination of H2 as part of the mechanism of nitrogenase is not sustained. [ABSTRACT FROM AUTHOR]

Density functional calculations reveal that protonation of a μ3-S in [Fe4S4X4]2- clusters (X = halide, thiolate, phenoxide) results in the breaking of one S-Fe bond (to >3 Å, from 2.3 Å). This creates a doubly-bridging SH ligand (μ3-SH is not stable), and a unique three-coordinated planar Fe atom. The under-coordination of this unique Fe atom is the basis of revised mechanisms for the acid-catalysed ligand substitution reactions in which substitution of X by PhS occurs at the unique Fe site by an indirect pathway involving initial displacement of X by acetonitrile (solvent), followed by displacement of coordinated acetonitrile by PhSH. When X = Cl or Br the rate of attack by PhSH is slower than the dissociation of X-, and is the rate-determining step; in contrast, when X = SEt, SBut or OPh the rate of dissociation of XH is slower than attack by PhSH and is ratedetermining for these clusters. A full and consistent interpretation of all kinetic data is presented including new explanations of many of the kinetic observations on the acid-catalysed substitution reactions of [Fe4S4X4]2- clusters. The proposed mechanisms are supported by density functional calculations of the structures of intermediates, and simulations of some of the steps. These findings are expected to have widespread ramifications for the reaction chemistry of both natural and synthetic clusters with the {Fe4S4} core. [ABSTRACT FROM AUTHOR]

Density functional calculations show that Fe-S clusters undergo unexpected large structural changes when protonated at S. Protonation of prototypical cubanoid [Fe4S4X4]2- to [Fe4S3(SH)X4]- (X = Cl, SR, OR) results in formation of doubly-bridging SH, severance of one Fe-S bond, and creation of a three-coordinate Fe. These findings explain previously enigmatic results concerning the reactivity of these clusters, including the rates of protonation, pKa data, and the kinetics of acid-catalysed ligand substitution. [ABSTRACT FROM AUTHOR]

Nitrogenase naturally converts N2 to NH3, but it also hydrogenates a variety of small molecules, in many cases requiring multiple electrons plus protons for each catalytic cycle. A general mechanism, arising from many density functional calculations and simulations, is proposed to account for all of these reactions. Protons, supplied serially in conjunction with electrons to the active site FeMo-co (a CFe7MoS9 (homocitrate) cluster), generate H atoms that migrate over and populate two S and two Fe atoms in the reaction domain. The mechanistic paradigm is conceptually straightforward: substrate (on Fe) and H atoms (on S and Fe) are bound contiguously in the reaction zone, and H atoms transfer (probably with some quantum tunneling) to the substrate to form product. Details and justifications of the mechanisms for N2 and other key substrates are summarised, and the unusual structure of FeMo-co as a general hydrogenation catalyst is rationalised. Testing experiments are suggested. [ABSTRACT FROM AUTHOR]

Nitrogenase enzymes containing molybdenum normally reduce N2to NH3, and are severely inhibited by CO, but vanadium-nitrogenase reduces CO to hydrocarbons C2H4, C2H6and C3H8. Aspects of the mechanism of this unexpected and unprecedented reaction have been investigated by density functional simulations of the iron-vanadium cofactor FeV-co [NFe7VS9(homocitrate)] protein-bound by cysteine and histidine. It is found that the intramolecular hydrogenating machinery previously proposed for N2reduction (including H-atom tunneling) can also effect reduction of CO. There are feasible steps for all of the requisite components of the overall reaction, namely (i) the binding of CO, (ii) the initial hydrogenation of CO to HCO, (iii) continued hydrogenations of CO at both C and O to HCOH and H2COH, (iv) eliminations of O as H2O, and (v) the C–C bond formation steps. Intermediate organic fragments can migrate around the active face of FeV-co, and hydrogen bonding between COH functions and S or SH components of FeV-co can occur and contribute to the stabilisation and orientation of intermediates. It is suggested that the difference between Mo-nitrogenase and V-nitrogenase occurs in the immediately surrounding protein, which facilitates (possibly viawater associated with homocitrate bound to V) the exogenous protonation and dehydration of –COH intermediates. [ABSTRACT FROM AUTHOR]

The crystallisation and resulting crystal structures of complexes [M(4′-Ph-terpy)2](PF6)2(4′-Ph-terpy = 4′-phenyl-2,2′ : 6′,2″-terpyridine) are described. Three crystal structure types retain the 2D terpy embrace (2D-TE) layers common in crystals of unsubstituted [Mterpy)2]2+complexes, while one structure type has the phenyl substituents intercalated into the 2D-TE, generating 1D terpy embrace chains. Where the 2D-TE is retained there are edge-to-face (EF) or offset-face-to-face (OFF) interactions between the phenyl substituents in the interlayer domain which also contains solvent, while in the intercalated structure the phenyl substituents engage the outer pyridyl rings of terpy in EF and OFF interactions. Anions occupy the major grooves, as usual. Solvent identity is influential, but enigmatic. [ABSTRACT FROM AUTHOR]