Preparation and application of achiral UiO-66-NH2 MOFs for enantioselective fluorescent detection of lysine enantiomers.

Lysine (Lys) is an essential nutrient that plays a crucial role in the growth and development of living organisms. Chiral analysis of Lys holds significant importance for ensuring the safety of food, pharmaceuticals, and health products. In this work, an achiral Zr-based metal organic frameworks (MOFs), UiO-66-NH2, was proposed as a fluorescent probe to achieve rapid response to l-lysine (L-Lys) in solution. Additionally, Zr4+ in the skeleton of UiO-66-NH2 framework exhibited different binding capacities towards Lys enantiomers, leading to distinct fluorescence responses for L-Lys and d-lysine (D-Lys). Leveraging these properties, the UiO-66-NH2 probe enabled accurate determination of L-Lys concentrations in solution, as well as the enantiomeric excess (ee) values of Lys solutions. Notably, in the detection of Lys enantiomers, the achiral UiO-66-NH2 acted as both a chiral selector and a fluorescent indicator, greatly improving the efficiency and stability of the detection system. The probable mechanism was further elucidated by pH titration experiments and density functional theory calculations. Additionally, the general applicability of this mechanism was validated by similar amino MOFs. The application of the UiO-66-NH2 fluorescent probe in analysis of infant formula milk powders and liquid milk samples confirmed the reliability of the method. Moreover, the construction of fluorescence test paper by immobilizing UiO-66-NH2 onto filler papers enabled the rapid identification of Lys enantiomers. Compared to previous fluorescent analyses of chiral amino acids assisted by additional metal ions, this study presented a novel approach and methodology that offers high efficiency, stability, reproducibility and reusability for the identification and detection of Lys enantiomers, highlighting the potential of the UiO-66-NH2 fluorescent probe in advancing analytical techniques.

Enantioselectivity in Vanadium-Dependent Haloperoxidases of Different Marine Sources for Sulfide Oxidation to Sulfoxides.

This study explores the reasons behind the variations in the enantioselectivity of the sulfoxidation of methyl phenyl sulfide by marine-derived vanadium-dependent haloperoxidases (VHPOs). Twelve new VHPOs of marine organisms were overexpressed, purified, and tested for their ability to oxidize sulfide. Most of these marine enzymes exhibited nonenantioselective behavior, underscoring the uniqueness of AnVBPO from the brown seaweed Ascophyllum nodosum and CpVBPO from the red seaweed Corallina pilulifera, which produce (R)- and (S)-sulfoxides, respectively. The enantioselective sulfoxidation pathway is likely due to direct oxygen transfer within the VHPO active site. This was demonstrated through molecular docking and molecular dynamics simulations, which revealed differences in the positioning of sulfide within AnVBPO and CpVBPO, thus explaining their distinct enantioselectivities. Nonenantioselective VHPOs probably follow a different oxidation pathway, initiating with sulfide oxidation to form a positively charged radical. Further insights were gained from studying the catalytic effect of VO43- on H2O2-driven sulfoxidation. This research improves the understanding of VHPO-mediated sulfoxidation and aids in developing biocatalysts for sulfoxide synthesis.

Review of Applications of ß-Cyclodextrin as a Chiral Selector for Effective Enantioseparation.

The significance and necessity of separating enantiomers in food, pharmaceuticals, pesticides, and other samples remains constant and unrelenting. The successful chiral separation usually includes the application of a chiral auxiliary compound, known also as a chiral selector (CS), that forms complexes with enantiomers of different physicochemical properties, enabling efficient separation. While both native and substituted cyclodextrins (CDs) are commonly used as CSs, ß-CD is undoubtedly the most popular one among them. This review includes recent advancements in the application of ß-CD as a CS. While the theoretical background behind the enantioseparation is also part of this work, the main emphasis is put on the factors that affect the efficacy of this process such as temperature, pH, solvent, and the choice of other additives. Also, the different analytical methods: Nuclear Magnetic Resonance (NMR) spectroscopy, Capillary Electrophoresis (CE), fluorescence spectroscopy (FS), High-Performance Liquid Chromatography (HPLC), Isothermal Titration Calorimetry (ITC), and UV-vis spectroscopy, used for enantioseparation with the aid of ß-CD as CS, are thoroughly compared. Also, since some of the chiral compounds have been studied in the context of their enantioseparation more than once, those works are compared and critically analyzed. In conclusion, while ß-CD can be in most cases used as CS, the choice of the experimental conditions and method of analysis is crucial to achieve the success.

Mechanisms in the Synthesis of S-Alcohols with 1,4-NADH Biomimetic Co-factor N-Benzyl-1,4-dihydronicotinamide using Horse Liver Alcohol Dehydrogenase: A Hybrid Computational Study.

The enantioselective reduction of prochiral ketones catalyzed by horse liver alcohol dehydrogenase (HLADH), was investigated via a hybrid computational approach, for molecular reactions involved in chiral synthesis of S-alcohols, when the natural co-factor, 1,4-dihyronicotinamide adenine dinucleotide, 1,4-NADH, was replaced with biomimetic co-factor, N-benzyl-1,4-dihydronicotinamide, 1.  We surmised that different hydride and proton transfer mechanisms were involved using co-factor, 1. An alternative mechanism, where the hydride transfer step occurred, via an η1-keto-S-η2-5,6-1,4-dihydronicotinamide-Zn(II) complex, was previously investigated with a model of the HLADH-Zn(II) catalytic site (J. Organometal. Chem. 2021, 943, 121810).  Presently, we studied canonical and alternative mechanisms compared to models of the entire enzyme structure.  We disproved the η2-Zn(II) complex, and discovered a canonical hydride transfer from biomimetic 1,4-NADH, 1, to the Zn(II) bound prochiral ketone substrate, followed by a new proton relay, consisting of a water chain connecting His51 to Ser48 that accomplished the S-alkoxy anion's protonation to yield the final S-alcohol product. The HLADH catalysis, with biomimetic co-factor, 1, that replaced the ribose group, the 5'-diphosphate groups, and the adenine nucleotide with a N-benzyl group, has provided a new paradigm for the design of other structures of 1,4-NADH biomimetic co-factors, including their economic value in biocatalysis reactions.

Comprehensive study of chiral herbicide flusulfinam uptake, translocation, degradation, and subcellular distribution in rice (Oryza sativa L.).

The biological behavior of flusulfinam, a potential commercial chiral herbicide for rice, has not been well explored. Herein, the uptake of chiral flusulfinam by rice and its transport, degradation, and subcellular distribution in rice (Oryza sativa L.) were investigated. The enantiomeric fraction (EF) in roots was 0.54 during 0 d to 7 d in hydroponic laboratory conditions. The bioconcentration factor of flusulfinam enantiomers was 2.1, suggesting an absence of observed enantioselectivity in the absorption process. Notably, the EF in the shoots decreased to 0.35 on the 7th day. The translocation factors of R- and S-flusulfinam were 0.12 and 0.27, respectively, indicating a preferential transfer of the S-flusulfinam from the root to the shoot. Flusulfinam was identified in the root after spraying. The translocation factors of R- and S-flusulfinam were consistently similar, signifying the capacity for downward movement without enantioselectivity. Interestingly, the degradation half-lives of R- and S-flusulfinam in the total plant were 5.50 and 5.06 d (p < 0.05), respectively, supporting the preferential degradation of S-flusulfinam throughout the total plant. Flusulfinam primarily entered the roots via the apoplastic pathway and was subsequently transported within the plant through aquaporins and ion channels. The subcellular distribution experiment revealed the predominant accumulation of flusulfinam enantiomers in soluble components (84%) with no enantioselectivity in these processes. There was upregulation lipid transfer protein-2 and carboxylesterases15 genes, which could explain the preferential transport and degradation of S-flusulfinam. This study is important in assessing the environmental risk associated with flusulfinam and ensuring food safety.

Enantiomer Recognition by the Difference in Adsorption Rates on the Surfaces of Chiral Crystals.

The chirality of biopolymers remains one of the mysteries of Life. For such objects, the phenomenon of supramolecular chirality (SMC) is vital. Enantiomers can be recognized by the adsorption on surfaces with SMC. However, the mechanisms of such chiral recognition are still unknown. In this work, the adsorption kinetics of menthol test enantiomers on the surfaces of γ-glycine and NiSO4•6H2O chiral crystals was studied. It was found that the difference in adsorption was observed in nonequilibrium state more often than in equilibrium. If the enantioselectivity in equilibrium state was observed, the enantioselectivity coefficient α at nonequilibrium conditions was higher. The maximum α in nonequilibrium state was 2.44 for γ-glycine crystals and 2.12 for NiSO4•6H2O crystals. Even if no differences in adsorption were observed under adsorption-desorption equilibrium conditions, a significant enantioselectivity at nonequilibrium conditions was found. This has proved the possibility of chiral recognition on surfaces with SMC by the differences in adsorption rates. Such novel chiral recognition mechanism can provide enhanced enantioselectivity in adsorption, catalysis, chromatographic separation, and chemical sensing.

Diastereoselective and Enantioselective Hydrophosphinylations of Conjugated Enynes, Allenes and Dienes via Synergistic Pd/Co Catalysis.

Different from the reported work focusing on the construction of single P- or C-stereocenter via hydrophosphinylation of unsaturated carbon bonds, the highly diastereo- and enantioselective hydrophosphinylation reaction of allenes, conjugated enynes and 1,3-dienes is achieved via a designed Pd/Co dual catalysis and newly modified masked phosphinylating reagent. A series of allyl motifs bearing both a tertiary C- and P-stereocenter are prepared in generally good yields, >20:1 dr, >20:1 rr and 99% ee. The unprecedented diastereo- and enantioselective hydrophosphinylation of 1,3-enynes is established to generate skeletons containing both a P-stereocenter and a nonadjacent chiral axis. The first stereodivergent hydrophosphinylation reaction is also developed to achieve all four P-containing stereoisomers. The present protocol features the use of only 3-minutes reaction time and 0.1% catalyst, and with the observation of up to 730 TON. A set of mechanistic studies reveal the necessity and roles of two metal catalysts and corroborate the designed synergistic process.

Stereoselective Vinylic C-H Addition via Metallaphotoredox Migration.

Geometrically defined allylic alcohols with SE, SZ, RE and RZ stereoisomers serve as valuable intermediates in synthetic chemistry, attributed to the stereoselective transformations enabled by the alkenyl and hydroxyl functionalities. When an ideal scenario presents itself with four distinct stereoisomers as potential products, the simultaneous control vicinal stereochemistry in a single step would offer a direct pathway to any desired stereoisomer. Here, we unveil a metallaphotoredox migration strategy to access stereodefined allylic alcohols through vinylic C-H activation with aldehydes. This method harnesses a chiral nickel catalyst in concert with a photocatalyst to enable a 1,4-Ni migration by using readily accessible 2-vinyl iodoarenes as starting materials. The efficacy of this methodology is highlighted by the precise construction of all stereoisomers of allylic alcohols bearing analogous substituents and the efficient synthesis of key intermediates en route to Myristinin family. Experimental and computational studies have shed light on pivotal aspects including the synergy of metal catalysis and photocatalysis, the driving forces behind the migration, and the determination of absolute configuration in the C-H addition process.

Radical-Based Enantioconvergent Reductive Couplings of Racemic Allenes and Aldehydes.

Transition metal-catalyzed radical-based enantioconvergent reactions have become a powerful strategy to synthesize enantiopure compounds from racemic starting materials. However, existing methods primarily address precursors with central chirality, neglecting those with axial chirality. Herein, we describe the enantioconvergent reductive coupling of racemic allenes with aldehydes, facilitated by a photoredox, chromium, and cobalt triple catalysis system. This method selectively affords one product from sixteen possible regio- and stereoisomers. The protocol leverages CoIII-H mediated hydrogen atom transfer (MHAT) and Cr-catalyzed radical-polar crossover for efficient stereoablation of axial chirality and asymmetric addition, respectively. Supported by mechanistic insights from control experiments, deuterium labeling, and DFT calculations, our approach offers synthetic chemists a valuable tool for creating enantioenriched chiral homoallylic alcohols, promising to advance radical-based strategies for synthesizing complex chiral molecules.

Enantioselectively generating imidazolone dIz by the chiral DNA intercalating and "light-switching" Ru(II) polypyridyl complex via a novel flash-quench method.

The 2-aminoimidazolone is a major and ubiquitous in vitro product of guanine oxidation. The flash-quench method, combining spectroscopy and product analysis, offers a novel and tunable approach to study guanine oxidation on double helical DNA. Herein we found that imidazolone dIz (2-amino-5-[(2-deoxy-ß-D-erythro-pentofuranosyl)amino]-4H-imidazole-4-one) and dZ (2,2-diamino-5-[2-deoxy-ß-D-erythro-pentofuranosyl)amino]-5(2H)-oxazolone) were the major oxidation products of double-strand DNA from the visible-light irradiation of the well-known DNA intercalating and light-switching Ru(OP)2dppz2+ (OP = 1,10-phenanthroline, dppz = dipyrido [3,2-a:2',3'-c]phenazine) in the presence of a typical quencher methyl viologen (MV2+). Using ESR spin-trapping method, the radical intermediate MV•+ with typical hyperfine pattern was detected which indicated the successful formation of the corresponding Ru3+ intercalated oxidant. The formation of dIz and dZ decreased markedly with the addition of nitrotetrazolium blue chloride (NBT), a typical O2•- reactant. With a more specific and highly sensitive O2•- probe CT02-H, its ESR signal decayed rapidly in the presence of Ru(OP)2dppz2+ and MV2+, suggesting that O2•- was indeed produced. More interestingly, enantio-selective generation of oxidation products from dsDNA was observed with the two chiral forms of Ru(OP)2dppz2+. This represents the first report that the flash-quench technique with MV2+ as the quencher can oxidize dsDNA effectively to form dIz and dZ via the Ru3+/O2•- mediated mechanism. Our new findings provide a novel method to generate two radicals simultaneously, G (-H)• and O2•-, in close proximity to one another in dsDNA.

Ni-Catalyzed Enantioselective Reductive Cyclization/Amidation and Amination of 1,6-Enynes and 1,7-Enynes.

Transition-metal-catalyzed hydroamination of unsaturated hydrocarbons is an appealing synthetic tool for the construction of high value-added chiral amines. Despite significant progress in the asymmetric hydroamination of alkenes, allenes, and 1,3-dienes, asymmetric hydroamination of 1,6-enynes or 1,7-enynes remains rather limited due to the enormous challenges in controlling the chemoselectivity and stereoselectivity of the reaction. Herein, we report a Ni-catalyzed chemo- and enantioselective reductive cyclization/amidation and amination of 1,6-enynes and 1,7-enynes using dioxazolones or anthranils as nitrene-transfer reagents. This mild, modular, and practical protocol provides rapid access to a variety of enantioenriched 2-pyrrolidone and 2-piperidone derivatives bearing an aminomethylene group at the 4-position in good yields (up to 83%) with excellent enantioselectivities (40 examples, up to 99% ee). Mechanistic experiments and density functional theory calculations indicate that the reaction is initiated by hydronickelation of alkynes followed by migratory insertion into alkenes, rather than by a [2+2+1] oxidative addition process of nickel to alkenes and alkynes.

A thiopyridine-bound mirror-image copper center in an artificial non-heme metalloenzyme.

Artificial metalloenzymes, in which a metal complex and protein matrix are combined, have been synthesized to catalyze stereoselective reactions using the chiral environment provided by the protein cavity. Artificial metalloenzymes can be engineered by the chemical modification and mutagenesis of the protein matrix. We developed artificial non-heme metalloenzymes using a cupin superfamily protein (TM1459) with a 4-His tetrad-metal-binding motif. The Cu-bound H52A/C106D mutant with 3-His triad showed a S-enantioselective Michael addition of nitromethane to α,ß-unsaturated ketone, 2-aza-chalcone 1. In this study, we demonstrated a chemical modification near the copper-binding site of this mutant to reverse its enantioselectivity. For chemical modification, the amino acid on the Si-face of the binding state of 1 to the copper center was replaced with Cys, followed by reaction with 4,4'-dithiopyridine (4-PDS) to form S-(pyridin-4-ylthio)cysteine (Cys-4py). Cu-bound I49C-4py/H52A/C106D showed reversal of the enantioselectivity from S-form to R-form (ee = 71%, (R)). The effect of steric hindrance of the amino acids at position 49 on enantioselectivity was investigated using I49X/H52A/C106D mutants (X = A, C, I, F, and W). Additionally, chemical modification with 2,2'-dithiopyridine (2-PDS) produced I49-2py/H52A/C106D, which showed lower R-enantioselectivity than I49-4py/H52A/C106D. Among the mutants, the 4py-modification on the Si-face was the most effective in reversing the enantioselectivity. By tuning the Re-face side, the H54A mutation introduced into the I49C-4py/H52A/C106D increased the R-enantioselectivity (ee = 88%, (R)). X-ray crystallography revealed a coordinated structure with ligation of thiopyridine in Cu-bound I49C-4py/H52A/H54A/C106D.

Gold(I)-Catalyzed Desymmetrization of Homopropargylic Alcohols via Cycloisomerization: Enantioselective Synthesis of Cyclopentenes Featuring a Quaternary Chiral Center.

Cyclopentene rings possessing a chiral quaternary center are important structural motifs found in various natural products. In this work, we disclose expedient and efficient access to this class of synthetically valuable structures via highly enantioselective desymmetrization of prochiral propargylic alcohols. The efficient chirality induction in this asymmetric gold catalysis is achieved via two-point bindings between a gold catalyst featuring a bifunctional phosphine ligand and the substrate homopropargylic alcohol moiety-an H-bonding interaction between the substrate HO group and a ligand phosphine oxide moiety and the gold-alkyne complexation. The propargylic alcohol substrates can be prepared readily via propargylation of enoate and ketone precursors. In addition to monocyclic cyclopentenes, spirocyclic and bicyclic ones are formed with additional neighboring chiral centers of flexible stereochemistry in addition to the quaternary center. This work represents rare gold-catalyzed highly enantioselective cycloisomerization of 1,5-enynes. Density functional theory (DFT) calculations support the chirality induction model and suggest that the rate acceleration enabled by the bifunctional ligand can be attributed to a facilitated protodeauration step at the end of the catalysis.

Catalytic Promiscuity of Fatty Acid Photodecarboxylase Enables Stereoselective Synthesis of Chiral α-Tetralones.

In the field of biocatalysis, discovering novel reactivity from known enzymes has been a longstanding challenge. Fatty acid photo-decarboxylase from Chlorella variabilis (CvFAP) has drawn considerable attention as a promising photoenzyme with potential green chemistry applications; however, its non-natural reactivity has rarely been exploited to date. Herein we report a non-natural reductive dehalogenation (deacetoxylation) reactivity of CvFAP inspired by its natural oxidative decarboxylation process, enabling the  stereoselective synthesis of a series of chiral α-substituted tetralones with high yields (up to 99%) and e.r. values (up to 99:1). Mechanistic studies demonstrated that the native photoenzyme catalyzed the reductive dehalogenation via a novel mechanism involving oxidized state (FADox) / semiquinone state (FADsq) redox pair and an electron transfer (ET)/proton transfer (PT) process of radical termination, distinct from the previous reports. To our knowledge, this study represents a new example of CvFAP promiscuity, and thus expands the reactivity repertoire of CvFAP and highlights the versatility of CvFAP in asymmetric synthesis.

Photoinduced Copper-Catalyzed Enantioselective Allylic C(sp3)-H Oxidation of Acyclic 1-Aryl-2-alkyl Alkenes as Limiting Substrates.

Herein, we disclose a simple copper-catalyzed method for enantioselective allylic C(sp3)-H oxidation of unsymmetrical acyclic alkenes, specifically 1-aryl-2-alkyl alkenes. The C-H substrates are used in limiting amounts, and the products are obtained with high enantioselectivity, E/Z-selectivity, and regioselectivity. The method exhibits broad functional group tolerance, and E/Z-alkene mixtures are suitable C-H substrates. The transformation is enabled by light irradiation, which sustains the enantioselective copper catalysis by photoinduced oxidant homolysis.

Nickel-Catalyzed α-selective Hydroalkylation of Vinylarenes.

C(sp3) centers adjacent to (hetero)aryl groups are widely present in physiologically active molecules. Metal-hydride-catalyzed hydroalkylation of alkenes represents an efficient means of forging C(sp3)-C(sp3) bonds, boasting advantages as a wide source of substrates, mild reaction conditions, and facile selectivity manipulation. Nevertheless, the hydroalkylation of vinylarenes encounters constraints in terms of substrate scope, necessitating the employment of activated alkyl halides or alkenes containing chelating groups, remains a challenge. In this context, we report a general nickel-hydride-catalyzed hydroalkylation protocol for vinylarenes. Remarkably, this system enables α-selective hydroalkylation of both aryl and heteroaryl alkenes under an extra ligand-free condition, demonstrating excellent coupling efficiency and selectivity. Furthermore, through the incorporation of chiral bisoxazoline ligands, we have achieved regio- and enantioselective hydroalkylation of vinylpyrroles, thereby facilitating the synthesis of α-branched alkylated pyrrole derivatives.

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and ß-substituted 5-hexenoic acids.

Enantioselective halolactonizations of sterically less hindered alkenoic acid substrates without substituents on the carbon-carbon double bond have remained a formidable challenge. To address this limitation, we report herein the asymmetric bromolactonization of 5-hexenoic acid derivatives catalyzed by a BINOL-derived chiral bifunctional sulfide.

Catalytic Enantioselective Friedel-Crafts Allenylation.

The first enantioselective Friedel-Crafts (FC) allenylation reaction for the creation of central chirality is developed under cooperative Ir(I)/(phosphoramidite,olefin) and Lewis acid catalysis. This enantioconvergent reaction utilizes racemic allenylic alcohol as the electrophile and shows compatibility with a variety of electron-rich arenes and heteroarenes. The resulting highly enantioenriched (up to >99.5:0.5 e.r.) 1,1-disubstituted allenylic methanes, bearing a benzylic carbon stereocenter, are obtained with complete regiocontrol - both on (hetero)arenes as well as on the allenylic fragment. This protocol allows for the enantioselective formal introduction of a 4-carbon alkyl chain into (hetero)arenes, along with the creation of a benzylic stereocenter. Judicious synthetic elaborations not only lead to formal enantioselective FC alkylation products of less electron-rich arenes but also of substituted arenes in ortho- and even meta-selective fashion. An intramolecular version of this FC allenylation is shown to proceed with promising enantioselectivity under the same catalytic conditions. Mechanistic studies revealed the involvement of dynamic kinetic asymmetric transformation (DyKAT) of racemic allenylic alcohols in this reaction.

Glucoconjugated Dinuclear Copper(II) Complex: An Efficient Catalyst for Stereoselective Synthesis of Trisubstituted Propargylamines via Solvent-free A3 Coupling Reaction.

Development of catalytic systems using nontoxic natural precursors is the need of the era, and along this line, we have synthesized a new D-glucose derived ligand (4,6-O-ethylidene-N-(2-hydroxy-4-(octyloxy)benzylidene)-ß-D-glucopyranosylamine) and its dinuclear copper(II) complex. The molecular structure of the complex has been established by single-crystal X-ray diffraction studies and detailed noncovalent intermolecular interactions present in it has been explored by Hirshfeld surface analysis. Further, the complex has been used as catalyst in the enantioselective (87-99% ee) synthesis of propargylamines in good to excellent yield (82-95%) via aldehyde-amines-alkynes (A3) coupling reaction under solvent-free condition. The formation of aminal intermediate during the reaction has been confirmed by 1H-NMR and single-crystal X-ray diffraction studies. The catalytic system is reusable without any appreciable loss in the enantioselectivity or product yield.

Carbonic Anhydrase Variants Catalyze the Reduction of Dialkyl Ketones with High Enantioselectivity.

Human carbonic anhydrase II (hCAII) naturally catalyzes the reaction between two achiral molecules-water and carbon dioxide-to yield the achiral product carbonic acid through a zinc hydroxide intermediate. We have previously shown that a zinc hydride, instead of a hydroxide, can be generated in this enzyme to create a catalyst for the reduction of aryl ketones. Dialkyl ketones are more challenging to reduce, and the enantioselective reduction of dialkyl ketones with two alkyl groups that are similar in size and electronic properties, is a particularly challenging transformation to achieve with high activity and selectivity. Here, we show that hCAII, as well as a double mutant of it, catalyzes the enantioselective reduction of dialkyl ketones with high yields and enantioselectivities, even when the two alkyl groups are similar in size. We also show that variants of hCAII catalyze the site-selective reduction of one ketone over the other in an unsymmetrical aliphatic diketone. Computational docking of a dialkyl ketone to variants of hCAII containing the zinc hydride provides insights into the origins of the reactivity of various substrates and the high enantioselectivity of the transformations and show how a confined environment can control the enantioselectivity of an abiological intermediate.