{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:57:31Z","timestamp":1760299051376,"version":"build-2065373602"},"reference-count":71,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2014,12,12]],"date-time":"2014-12-12T00:00:00Z","timestamp":1418342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nitrile hydratase (NHase, EC 4.2.1.84) is a metalloenzyme which catalyses the conversion of nitriles to amides. The high efficiency and broad substrate range of NHase have led to the successful application of this enzyme as a biocatalyst in the industrial syntheses of acrylamide and nicotinamide and in the bioremediation of nitrile waste. Crystal structures of both cobalt(III)- and iron(III)-dependent NHases reveal an unusual metal binding motif made up from six sequential amino acids and comprising two amide nitrogens from the peptide backbone and three cysteine-derived sulfur ligands, each at a different oxidation state (thiolate, sulfenate and sulfinate). Based on the active site geometry revealed by these crystal structures, we have designed a series of small-molecule ligands which integrate essential features of the NHase metal binding motif into a readily accessible peptide environment. We report the synthesis of ligands based on a pyridine-2,6-dicarboxylic acid scaffold and L-cysteine, L-S-methylcysteine, L-methionine or L-penicillamine. These ligands have been combined with cobalt(III) and iron(III) and tested as catalysts for biomimetic nitrile hydration. The highest levels of activity are observed with the L-penicillamine ligand which, in combination with cobalt(III), converts acetonitrile to acetamide at 1.25 turnovers and benzonitrile to benzamide at 1.20 turnovers.<\/jats:p>","DOI":"10.3390\/molecules191220751","type":"journal-article","created":{"date-parts":[[2014,12,12]],"date-time":"2014-12-12T10:06:43Z","timestamp":1418378803000},"page":"20751-20767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bio-Inspired Nitrile Hydration by Peptidic Ligands Based on  L-Cysteine, L-Methionine or L-Penicillamine and  Pyridine-2,6-dicarboxylic Acid"],"prefix":"10.3390","volume":"19","author":[{"given":"Cillian","family":"Byrne","sequence":"first","affiliation":[{"name":"School of Chemistry F11, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate","family":"Houlihan","sequence":"additional","affiliation":[{"name":"School of Chemistry F11, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prarthana","family":"Devi","sequence":"additional","affiliation":[{"name":"School of Chemistry F11, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Jensen","sequence":"additional","affiliation":[{"name":"School of Chemistry F11, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Rutledge","sequence":"additional","affiliation":[{"name":"School of Chemistry F11, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1039\/C2GC36534K","article-title":"Metal-catalyzed amide bond forming reactions in an environmentally friendly aqueous medium: Nitrile hydrations and beyond","volume":"15","author":"Crochet","year":"2013","journal-title":"Green Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.ccr.2010.08.018","article-title":"Frontiers in catalytic nitrile hydration: Nitrile and cyanohydrin hydration catalyzed by homogeneous organometallic complexes","volume":"255","author":"Ahmed","year":"2011","journal-title":"Coord. Chem. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ica.2004.04.029","article-title":"Metal-mediated and metal-catalyzed hydrolysis of nitriles","volume":"358","author":"Kukushkin","year":"2005","journal-title":"Inorg. Chim. Acta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1039\/C2CC35256G","article-title":"Bioinspired catalytic nitrile hydration by dithiolato, sulfinato\/thiolato, and sulfenato\/sulfinato ruthenium complexes","volume":"49","author":"Kumar","year":"2013","journal-title":"Chem. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9808","DOI":"10.1002\/chem.201001152","article-title":"Bis(allyl)ruthenium(IV) complexes containing water-soluble phosphane ligands: Synthesis, structure, and application as catalysts in the selective hydration of organonitriles into amides","volume":"16","author":"Cadierno","year":"2010","journal-title":"Chem. Eur. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1002\/chem.200802264","article-title":"Nanoparticle-supported and magnetically recoverable ruthenium hydroxide catalyst: Efficient hydration of nitriles to amides in aqueous medium","volume":"15","author":"Polshettiwar","year":"2009","journal-title":"Chem. Eur. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6601","DOI":"10.1002\/chem.200800847","article-title":"Selective ruthenium-catalyzed hydration of nitriles to amides in pure aqueous medium under neutral conditions","volume":"14","author":"Cadierno","year":"2008","journal-title":"Chem. Eur. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1002\/anie.200800366","article-title":"Rh(I)-catalyzed hydration of organonitriles under ambient conditions","volume":"47","author":"Goto","year":"2008","journal-title":"Angew. Chem. Int. Edit."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4845","DOI":"10.1016\/S0040-4039(00)00743-7","article-title":"The hydration of nitriles catalyzed by water-soluble rhodium complexes","volume":"41","author":"Djoman","year":"2000","journal-title":"Tetrahedron Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1021\/ja3006012","article-title":"Palladium(II) containing gamma-keggin silicodecatungstate that efficiently catalyzes hydration of nitriles","volume":"134","author":"Hirano","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1016\/j.tetlet.2009.04.007","article-title":"An efficient Pd-catalyzed hydration of nitrile with acetaldoxime","volume":"50","author":"Kim","year":"2009","journal-title":"Tetrahedron Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S1381-1169(00)00253-3","article-title":"The catalytic hydration of nitriles to amides using a homogeneous platinum phosphinito catalyst","volume":"160","author":"Ghaffar","year":"2000","journal-title":"J. Mol. Catal. A Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8657","DOI":"10.1016\/0040-4039(95)01785-G","article-title":"A new homogeneous platinum-containing catalyst for the hydrolysis of nitriles","volume":"36","author":"Ghaffar","year":"1995","journal-title":"Tetrahedron Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/adsc.201100812","article-title":"An efficient and practical protocol for catalytic hydrolysis of nitriles by a copper(I) complex in water","volume":"354","author":"Li","year":"2012","journal-title":"Adv. Synth. Catal."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mitsudome, T., Mikami, Y., Mori, H., Arita, S., Mizugaki, T., Jitsukawa, K., and Kaneda, K. (2009). Supported silver nanoparticle catalyst for selective hydration of nitriles to amides in water. Chem. Commun., 3258\u20133260.","DOI":"10.1039\/b902469g"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1002\/cssc.201200203","article-title":"A general and efficient heterogeneous gold-catalyzed hydration of nitriles in neat water under mild atmospheric conditions","volume":"5","author":"Liu","year":"2012","journal-title":"ChemSusChem"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8695","DOI":"10.1002\/chem.200901231","article-title":"Gold activation of nitriles: Catalytic hydration to amides","volume":"15","author":"Ramon","year":"2009","journal-title":"Chem. Eur. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1039\/c2gc16637b","article-title":"Efficient and practical transition metal-free catalytic hydration of organonitriles to amides","volume":"14","author":"Tu","year":"2012","journal-title":"Green Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1039\/C2RA22868H","article-title":"Transition metal-free 1,3-dimethylimidazolium hydrogen carbonate catalyzed hydration of organonitriles to amides","volume":"3","author":"Verma","year":"2013","journal-title":"RSC Adv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5598","DOI":"10.1021\/ol902309z","article-title":"Anhydrous hydration of nitriles to amides using aldoximes as the water source","volume":"11","author":"Lee","year":"2009","journal-title":"Org. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1016\/j.tetlet.2010.01.063","article-title":"An efficient InCl3-catalyzed hydration of nitriles to amides: Acetaldoxime as an effective water surrogate","volume":"51","author":"Kim","year":"2010","journal-title":"Tetrahedron Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1006\/bbrc.2001.5897","article-title":"Crystal structure of cobalt-containing nitrile hydratase","volume":"288","author":"Miyanaga","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/nbt0898-733","article-title":"Metalloenzyme nitrile hydratase: Structure, regulation, and application to biotechnology","volume":"16","author":"Kobayashi","year":"1998","journal-title":"Nat. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/0167-7799(92)90283-2","article-title":"Enzymatic synthesis of acrylamide: A success story not yet over","volume":"10","author":"Kobayashi","year":"1992","journal-title":"Trends Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1385\/ABAB:79:1-3:671","article-title":"Bioconversion of acrylonitrile to acrylamide using a thermostable nitrile hydratase","volume":"77\u201379","author":"Padmakumar","year":"1999","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s11244-005-3817-1","article-title":"Enantioselective biotransformations of nitriles in organic synthesis","volume":"35","author":"Wang","year":"2005","journal-title":"Top. Catal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.biotechadv.2010.05.020","article-title":"Nitrile hydratases (NHases): At the interface of academia and industry","volume":"28","author":"Prasad","year":"2010","journal-title":"Biotechnol. Adv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nsb0598-347","article-title":"Novel non-heme iron center of nitrile hydratase with a claw setting of oxygen atoms","volume":"5","author":"Shigehiro","year":"1998","journal-title":"Nat. Struct. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0010-8545(01)00413-1","article-title":"Structural and functional models of nitrile hydratase","volume":"225","author":"Mascharak","year":"2002","journal-title":"Coord. Chem. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1021\/cr020619e","article-title":"Synthetic analogues of cysteinate-ligated non-heme iron and non-corrinoid cobalt enzymes","volume":"104","author":"Kovacs","year":"2004","journal-title":"Chem. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1021\/ja410462j","article-title":"The active site sulfenic acid ligand in nitrile hydratases can function as a nucleophile","volume":"136","author":"Martinez","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1002\/ejic.200701137","article-title":"Theoretical investigation of the second-shell mechanism of nitrile hydratase","volume":"2008","author":"Hopmann","year":"2008","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1021\/ic500091k","article-title":"Full reaction mechanism of nitrile hydratase: A cyclic intermediate and an unexpected disulfide switch","volume":"53","author":"Hopmann","year":"2014","journal-title":"Inorg. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5751","DOI":"10.1021\/ic030088s","article-title":"Modulation of the pKa of metal-bound water via oxidation of thiolato sulfur in model complexes of Co(III) containing nitrile hydratase: Insight into possible effect of cysteine oxidation in Co-nitrile hydratase","volume":"42","author":"Tyler","year":"2003","journal-title":"Inorg. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1021\/ja9833523","article-title":"Co(III) complexes with carboxamido N and thiolato S donor centers: Models for the active site of Co-containing nitrile hydratases","volume":"121","author":"Noveron","year":"1999","journal-title":"J. Am. Chem. Soc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3526","DOI":"10.1002\/(SICI)1521-3773(19991203)38:23<3526::AID-ANIE3526>3.0.CO;2-Z","article-title":"A pentacoordinated di-N-carboxamido-dithiolato-O-sulfinato-iron(III) complex related to the metal site of nitrile hydratase","volume":"38","author":"Heinrich","year":"1999","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1002\/1099-0682(200109)2001:9<2203::AID-EJIC2203>3.0.CO;2-A","article-title":"Cobalt(III) complexes with carboxamido-N and sulfenato-S or sulfinato-S ligands suggest that a coordinated sulfenate-S is essential for the catalytic activity of nitrile hydratases","volume":"2001","author":"Heinrich","year":"2001","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0010-8545(99)00101-0","article-title":"Nitrile hydratase and related non-heme iron sulfur complexes","volume":"192","author":"Artaud","year":"1999","journal-title":"Coord. Chem. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6162","DOI":"10.1002\/anie.200500814","article-title":"Direct synthesis of a thiolato-S and sulfinato-S Co(III) complex related to the active site of nitrile hydratase: A pathway to the post-translational oxidation of the protein","volume":"44","author":"Bourles","year":"2005","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11211","DOI":"10.1021\/ja062706k","article-title":"How does single oxygen atom addition affect the properties of an Fe-nitrile hydratase analogue? The compensatory role of the unmodified thiolate","volume":"128","author":"Dey","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11417","DOI":"10.1021\/ja012555f","article-title":"The first example of a nitrile hydratase model complex that reversibly binds nitriles","volume":"124","author":"Shearer","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.tet.2004.10.041","article-title":"Design and synthesis of an isopenicillin N synthase mimic","volume":"61","author":"Krall","year":"2005","journal-title":"Tetrahedron"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Barry, S.M., and Rutledge, P.J. (2008). Cis-dihydroxylation of alkenes by a non-heme iron enzyme mimic. Synlett, 2172\u20132174.","DOI":"10.1055\/s-2008-1078248"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1039\/b921934j","article-title":"Design and synthesis of a tetradentate \u201c3-amine-1-carboxylate\u201d ligand to mimic the metal binding environment at the non-heme iron(II) oxidase active site","volume":"8","author":"Dungan","year":"2010","journal-title":"Org. Biomol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7372","DOI":"10.1039\/c2ob25834j","article-title":"Investigating the cis-dihydroxylation of alkenes by non-heme iron enzyme mimics","volume":"10","author":"Barry","year":"2012","journal-title":"Org. Biomol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1016\/j.tet.2012.02.031","article-title":"L-Proline-derived ligands to mimic the \u201c2-his-1-carboxylate\u201d triad of the non-heme iron oxidase active site","volume":"68","author":"Dungan","year":"2012","journal-title":"Tetrahedron"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/j.tetlet.2012.12.095","article-title":"L-Proline derived mimics of the non-heme iron active site catalyse allylic oxidation in acetonitrile solutions","volume":"54","author":"Dungan","year":"2013","journal-title":"Tetrahedron Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1021\/jo00208a022","article-title":"Total synthesis of (+)-sparsomycin\u2014Approaches using cysteine and serine inversion","volume":"50","author":"Hwang","year":"1985","journal-title":"J. Org. Chem."},{"key":"ref_49","unstructured":"Hafner, K., Rees, C.W., Trost, B.M., Lehn, J.M., Schleyer, P.V.R., and Zahruchik, R. (1984). Reactivity and Structure Concepts in Organic Chemistry, Springer-Verlag."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1021\/ja02263a012","article-title":"The methyl ester of orthobenzoyl-benzoic acid","volume":"38","author":"McMullen","year":"1916","journal-title":"J. Am. Chem. Soc."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Bocchi, V., Casnati, G., Dossena, A., and Marchelli, R. (1979). Esterification of amino acids and dipeptides under mild conditions; part ii: Via sodium salts. Synthesis, 961\u2013962.","DOI":"10.1055\/s-1979-28889"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1016\/j.tet.2004.01.020","article-title":"Recent development of peptide coupling reagents in organic synthesis","volume":"60","author":"Han","year":"2004","journal-title":"Tetrahedron"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/(SICI)1099-0682(199906)1999:6<1001::AID-EJIC1001>3.0.CO;2-M","article-title":"Novel chiral pyridine N-oxide ligands and their application in the enantioselective catalytic reduction of ketones and the addition of diethylzinc to aldehydes","volume":"1999","author":"Derdau","year":"1999","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_54","first-page":"1197","article-title":"New membranes with mercapto-2,6-pyridinediamides as anion recognition fixed sites","volume":"61","author":"Alexie","year":"2010","journal-title":"Rev. Chim."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Loconto, P.R. (2005). Trace Environmental Quantitative Analysis\u2014Principles, Techniques and Applications, Marcel Dekker Inc.. [2nd ed.].","DOI":"10.1201\/9781420030563"},{"key":"ref_56","unstructured":"Harris, D.C. (2003). Quantitative Chemical Analysis, W.H. Freeman. [6th ed.]."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1002\/1099-0682(200106)2001:6<1407::AID-EJIC1407>3.0.CO;2-P","article-title":"A bis(carboxamido-N)diisocyanidobis(sulfenato-S)cobalt(III) complex, model for the post-translational oxygenation of nitrile hydratase thiolato ligands","volume":"2001","author":"Heinrich","year":"2001","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1021\/jo00811a020","article-title":"Mercaptoethanol catalysis for hydrolysis of N-benzyl-3-cyanopyridinium bromide. A model for the nitrilase reaction","volume":"36","author":"Cordes","year":"1971","journal-title":"J. Org. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1021\/ja00816a014","article-title":"Kinetics studies of the hydrolysis of coordinated nitriles","volume":"96","author":"Balahura","year":"1974","journal-title":"J. Am. Chem. Soc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1002\/jlac.198419840905","article-title":"Oxidative deblocking of the 4-methoxybenzyl thioether protecting group: Application to the directed synthesis of poly-cystinyl peptides","volume":"1984","author":"Platen","year":"1984","journal-title":"Liebigs Ann. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1021\/ol026947i","article-title":"Mild and highly chemoselective oxidation of thioethers mediated by Sc(OTf)3","volume":"5","author":"Matteucci","year":"2003","journal-title":"Org. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1016\/j.tetlet.2010.04.059","article-title":"An efficient and scalable synthesis of N-(benzyloxycarbonyl)- and N-(methyloxycarbonyl)-(S)-vinylglycinol","volume":"51","author":"Lumbroso","year":"2010","journal-title":"Tetrahedron Lett."},{"key":"ref_63","unstructured":"Bruker (1995). Area Detector Control and Data Integration and Reduction Software, Bruker Analytical X-ray Instruments Inc."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S1472-7862(02)00030-8","article-title":"X-seed\u2014A software tool for supramolecular crystallography","volume":"1","author":"Barbour","year":"2001","journal-title":"J. Supramol. Chem."},{"key":"ref_65","unstructured":"Sheldrick, G.M. (1996). Sadabs. Empirical Absorption Correction Program for Area Detector Data, University of G\u00f6ttingen."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1107\/S0108767394005726","article-title":"An empirical correction for absorption anisotropy","volume":"51","author":"Blessing","year":"1995","journal-title":"Acta Crystallogr. Sect. A Found. Crystallogr."},{"key":"ref_67","unstructured":"Sheldrick, G.M. (1998). Shelx97 Programs for Crystal Structure Analysis, University of G\u00f6ttingen."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1107\/S0108767383001762","article-title":"On enantiomorph-polarity estimation","volume":"39","author":"Flack","year":"1983","journal-title":"Acta Crystallogr. Sect. A Found. Crystallogr."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1107\/S0108767385001064","article-title":"Least-squares absolute-structure refinement\u2014Practical experience and ancillary calculations","volume":"41","author":"Bernardinelli","year":"1985","journal-title":"Acta Crystallogr. Sect. A Found. Crystallogr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1107\/S0108767399004262","article-title":"Absolute structure and absolute configuration","volume":"55","author":"Flack","year":"1999","journal-title":"Acta Crystallogr. Sect. A Found. Crystallogr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1107\/S0021889800007184","article-title":"Reporting and evaluating absolute-structure and absolute-configuration determinations","volume":"33","author":"Flack","year":"2000","journal-title":"J. Appl. Crystallogr."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/19\/12\/20751\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:10:53Z","timestamp":1760217053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/19\/12\/20751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,12]]},"references-count":71,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2014,12]]}},"alternative-id":["molecules191220751"],"URL":"https:\/\/doi.org\/10.3390\/molecules191220751","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2014,12,12]]}}}