{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:34:39Z","timestamp":1791473679723,"version":"4.3.4"},"reference-count":65,"publisher":"Wiley","issue":"36","license":[{"start":{"date-parts":[[2010,8,27]],"date-time":"2010-08-27T00:00:00Z","timestamp":1282867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2010,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To ensure the quasi\u2010irreversibility of the oxidation of alcohols coupled with the reduction of ketones in a hydrogen\u2010transfer (HT) fashion, stoichiometric amounts of \u03b1\u2010halo carbonyl compounds have been employed as hydrogen acceptors. The reason that these substrates lead to quasi\u2010quantitative conversions has been tacitly attributed to both thermodynamic and kinetic effects. To provide a clear rationale for this behavior, we investigate herein the redox equilibrium of a selected series of ketones and 2\u2010propanol by undertaking a study that combines experimental and theoretical approaches. First, the activity of the (<jats:italic>R<\/jats:italic>)\u2010specific alcohol dehydrogenase from <jats:italic>Lactobacillus\u2005brevis<\/jats:italic> (LBADH) with these substrates was studied. The docking of acetophenone\/(<jats:italic>R<\/jats:italic>)\u20101\u2010phenyethanol and \u03b1\u2010chloroacetophenone\/(<jats:italic>S<\/jats:italic>)\u20102\u2010chloro\u20101\u2010phenylethanol in the active site of the enzyme confirms that there seems to be no structural reason for the lack of reactivity of halohydrins. This assumption is confirmed by the fact that the corresponding aluminum\u2010catalyzed Meerwein\u2013Ponndorf\u2013Verley\u2013Oppenauer (MPVO) reactions afford similar conversions to those obtained with LBADH, showing that the observed reactivity is independent of the catalyst employed. While the initial rates of the enzymatic reductions and the IR <jats:italic>\u03bd<\/jats:italic>(C\uf8feO) values contradict the general belief that electron\u2010withdrawing groups increase the electrophilicity of the carbonyl group, the calculated \u0394<jats:italic>G<\/jats:italic> values of the isodesmic redox transformations of these series of ketones\/alcohols with 2\u2010propanol\/acetone support the thermodynamic control of the reaction. As a result, a general method to predict the degree of conversion obtained in the HT\u2010reduction process of a given ketone based on the IR absorption band of the carbonyl group is proposed, and a strategy to achieve the HT oxidation of halohydrins is also shown.<\/jats:p>","DOI":"10.1002\/chem.201001233","type":"journal-article","created":{"date-parts":[[2010,8,30]],"date-time":"2010-08-30T22:08:27Z","timestamp":1283206107000},"page":"11012-11019","source":"Crossref","is-referenced-by-count":47,"title":["Ketone\u2013Alcohol Hydrogen\u2010Transfer Equilibria: Is the Biooxidation of Halohydrins Blocked?"],"prefix":"10.1002","volume":"16","author":[{"given":"Fabricio R.","family":"Bisogno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Garc\u00eda\u2010Urdiales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haydee","family":"Vald\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Lavandera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Kroutil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimas","family":"Su\u00e1rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Gotor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,8,27]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.145"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9781139167604"},{"key":"e_1_2_6_3_2","unstructured":"\u00a0"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1039\/b618340a"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar700134q"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1039\/B513396C"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1039\/B513564H"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200502702"},{"key":"e_1_2_6_8_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200502702"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2006.06.065"},{"key":"e_1_2_6_10_2","volume-title":"Modern Oxidation Methods","year":"2004"},{"key":"e_1_2_6_11_2","unstructured":"For some reviews see:"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.2174\/138527206778249621"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetasy.2005.08.058"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo010721w"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-1994-25625"},{"key":"e_1_2_6_16_2","unstructured":"For some recent bibliographies see:"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/9783527622481.ch8"},{"key":"e_1_2_6_18_2","first-page":"757","volume-title":"Biocatalysis in the Pharmaceutical and Biotechnology Industry","author":"Buchholz S.","year":"2007"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar7001073"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar700167a"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-007-1002-0"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr040640a"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2004.02.005"},{"key":"e_1_2_6_24_2","unstructured":"\u00a0"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1351\/pac200072071233"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1962206"},{"key":"e_1_2_6_27_2","unstructured":"For descriptions of protocols to shift the equilibrium in ADH\u2010catalyzed HT transformations"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1039\/b401065e"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/1522-2640(200207)74:7<1035::AID-CITE1035>3.0.CO;2-2"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo802350f"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol800549f"},{"key":"e_1_2_6_32_2","unstructured":"\u00a0"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.200606079"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.200606145"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jms.2005.11.010"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-1996-4381"},{"key":"e_1_2_6_37_2","unstructured":"\u00a0"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3757(20020315)114:6<1062::AID-ANGE1062>3.0.CO;2-R"},{"key":"e_1_2_6_38_3","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20020315)41:6<1020::AID-ANIE1020>3.0.CO;2-S"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol0162116"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo7016422"},{"key":"e_1_2_6_41_2","unstructured":"For other quasi\u2010irreversible bio\u2010 or metal\u2010catalyzed HT transformations that use other type of reagents see:"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.200900218"},{"key":"e_1_2_6_43_2","unstructured":"C.Peschko J.Stohrer Wacker ChemieAG(Germany) DE 102006009743 2007;"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol702029n"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2007.03.135"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.19660782203"},{"key":"e_1_2_6_46_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.196609471"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3757(20001201)112:23<4476::AID-ANGE4476>3.0.CO;2-C"},{"key":"e_1_2_6_47_3","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20001201)39:23<4306::AID-ANIE4306>3.0.CO;2-G"},{"key":"e_1_2_6_48_2","unstructured":"To ensure that these results were not only obtained with this short\u2010chain ADH due to any special feature we repeated these experiments with the NADH medium\u2010chain alcohol dehydrogenase fromRhodococcus\u2005ruberADH\u2010\u2032A\u2032 which showed a very similar trend. For more information see reference\u2005[8]."},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/BFb0103304"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.04.029"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/00404-0399(50)0946A-"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1039\/a900189a"},{"key":"e_1_2_6_53_2","unstructured":"To normalize the carbonyl IR frequencies so that structurally different ketones can be reliably compared a correction factor of 0.982 was applied to the IR frequencies of aliphatic substrates2\u2009gand2\u2009h. This factor comes from the division of the carbonyl stretching frequencies of acetophenone ($\\tilde \\nu $=1685\u2005cm\u22121) and acetone ($\\tilde \\nu $=1715\u2005cm\u22121). By doing so we have assumed that IR frequencies are only dependant on the strength of the carbonyl bond and the size of its substituents."},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1139\/v58-145"},{"key":"e_1_2_6_55_2","unstructured":"We chose1\u2009i\/2\u2009idue to the problems observed with substrate2\u2009hunder the HT conditions catalyzed by Al(OtBu)3. We have also performed the enzymatic reactions coupling of1\u2009c\/2\u2009cwith2\u2009h\/1\u2009h respectively obtaining similar results to the transformations shown in Scheme\u20052."},{"key":"e_1_2_6_56_2","unstructured":"This is due to the fact that after 24\u2005h the activity of LBADH and the effective concentration of NADP(H) considerably decrease (data not shown)."},{"key":"e_1_2_6_57_2","unstructured":"1010 Sherbrooke Street West Suite 910 Montr\u00e9al Qu\u00e9bec http:\/\/www.chemcomp.com."},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-987X(200009)21:12<1049::AID-JCC3>3.0.CO;2-F"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp046748b"},{"key":"e_1_2_6_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(98)00100-9"},{"key":"e_1_2_6_61_2","unstructured":"The PyMOL molecular graphics system W.\u2005L. DeLano DeLano Scientific San Carlos 2002 http:\/\/www.pymol.org."}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fchem.201001233","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.201001233","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T16:03:09Z","timestamp":1760284989000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.201001233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8,27]]},"references-count":65,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2010,9,24]]}},"alternative-id":["10.1002\/chem.201001233"],"URL":"https:\/\/doi.org\/10.1002\/chem.201001233","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,8,27]]}}}