Thomas EquinousA, Friar Berengar of SlaptonB and Günther SchlonkC*
Abstract: And on the eighth day, the Lord made dimeric µ-hydrido-µ-amidocalcium coordination complexes, and became distracted.
Specific: Transubstantiation is the process by which the bread and wine of the eucharist is said to become the body and blood of Christ. The mechanism of this transformation is, shall we say, vexed, and has been for some time. The theology of this miraculous reaction is beyond the scope of this paper and the understanding of its authors. This study seeks instead to examine the chemistry behind it.
Turning wine into blood represents a significant challenge to the synthetic chemist. Some of the earliest work in this field is attributed to the biblical Jesus, who undertook the simpler transformation of water into wine. Quite how he did this remains unknown, as the supporting information for the New Testament has not yet become available. This hole in the literature has led some to speculate as to his chosen reaction conditions. Venerable Professor Constantine from the Institute of Theological Chemistry in Antioch has postulated that he performed a high-pressure hydration of ethene.1 Basil II of Pfizantium has disputed Constantine’s theory, and instead claims that Jesus used the McGonagall transfiguration to convert H2O into H2C and an alpha particle.2 Given that it took centuries for metaphysical chemists to establish if the deity involved was monomeric or trimeric, we can’t expect this debate to be resolved any time soon.
Devine speciation aside, subsequent work was undertaken by either Jesus himself or an alumnus from his research group on the conversion of wine into blood. Sources differ on the vintage used, but all agree that the blood-group of the product was O-double-negative (O2-). The historical and dogmatic details of this reaction have been debated on-and-off for the last two millennia. Few if any scientific studies have been conducted on this topic, with the emphasis rather on philosophical minutia. This changed in 2021 with a study by Paul the Associate Professor.3 Paul wondered if everyone was overdoing the metaphysics, and if a simple chemical reaction was the root of this phenomenon. He hypothesised that an enzymatic reaction occurred as the eucharistic wine was consumed, converting the concoction’s chemical components into those of blood: specifically, heme B.
To test this theory, Paul brought an MS from his lab into a local church and asked the parishioners to gargle their Christ-blood while he collected samples. When this data was analysed, Paul detected the presence of heme B in the wine. He attributed this detection to the transubstantiation of the wine by the enzyme amylase (the primary digestive enzyme in saliva).3 We harboured some doubts about the veracity of this result. Paul usually uses that MS to analyse whole blood for illicit substances, and he does not mention cleaning it before conducting his experiment. Nor did he control for the parishioners having bitten their tongues in the time before sampling their Jesus-juice. However, we were intrigued by the prospect of an amylase-catalysed pathway from wine-components to heme-type porphyrins.
We decided to probe the mechanism by which this transformation occurs with chemical and computation analysis. A quick google search for human amylase revealed that the enzyme incorporates a calcium ion. This seemed a promising start, as everyone knows that metals catalyse stuff, and we like metals. We also conducted a survey of wine constituents in search of molecules with structures mappable onto a heme skeleton and came up with several matches (scheme 1). The most promising of these were linalool (a floral-smelling terpene), tartaric acid, fructose and the amino acid proline.
We sketched out several mechanistic pathways by which these molecules might form a heme-type porphyrin and sought to assess their viability with computational studies. We were able to find a pathway to heme from these components, but the energy barrier was such that the reaction would only proceed if performed at the centre of Jupiter. These results were in contradiction of the insistence of social-media effluencer and Egregious Professor Leonard Crony, who claims chemputation solves all problems. The study teetered and nearly collapsed but was saved by the appearance of a helpful paper clip, asking “it looks like you’re trying to model and enzymatic reaction, would you like some help?”. Clippy suggested we use a dimer of amylase, and Clippy was right. Tandem calcium-calcium catalysis was the answer to our mechanistic woes. The simulated mechanism was re-run with two units of amylase and gave the much more reasonable barrier of 90 kcal/mol.
While this theoretical mechanism was convincing, we decided to seek experimental support for it. Our initial experimental work was conducted with human 𝛼-amylase as catalyst. This was accomplished by bringing a bag of Eppendorfs to a wine- tasting and collecting “discarded samples”. Analysis of the reaction mixture by Transverse-Induction Proton Spectroscopy (TIPSY) detected the presence of a heme, but the reproducibility was too poor for useful kinetic information to be obtained. We addressed this issue by moving to a model system (1): a dimeric calcium complex with a ligand derived from the amino acids (L)- laterine and (R)-samaritine. Using this simpler catalyst, an extensive series of kinetic and computational experiments were performed. The details for these experiments are provided in the electronic unsupported information. The culmination of this study is a proposed catalytic cycle for conversion of linalool, tartaric acid, fructose and proline into heme 14:22 (scheme 2).
The restive state of the catalyst is dimeric μ-hydrido-μ- amidocalcium carboxylate 1. We’ve called it the restive state because it tends to become distracted and wander off if impurities are introduced. Linalool (2) breaks up dimer 1 and inserts into the Ca-N bond. The other calcium performs a simultaneous Reacharound rearrangement to close the first ring. Tartaric acid is then coordinated, deprotonated, dehydrated and defenestrated to give intermediate 6. The flavanol catechin (6A) reduces 6 to 7, acting in its much- acclaimed role as an antioxidant. Fructose (8) is folded into 7 via some Origami-type chemistry (9–11) and two more flavanol reductions. Finally, proline closes the porphyrin ring in a Garfunkel Decarbunkelation. Calcium is displaced by adventitious iron(II), somehow regenerating 1. The resultant heme 14:22 can undergo transesterification with ethyl herate (17) to form a heme-heretic ester such as heme 6:52 (18). At this point, the astute reader may have noticed several inconsistencies in this mechanism. Specifically, poor hydrogen- accounting, some missing oxygens and nitrogens appearing from nowhere by pnictogenesis. One might even accuse us possessing less rigour than last week’s celery. That may be the case, but hey, we never claimed to be infallible.
References
1. T. G. Constantine, 2017, Holy J. Chem. 23:14.
2. T. B. S. Basil, 2018, Laterine J. Chem. 7:19.
3. A. P. Paul, 2021, Byz. J.Chem. 42:5.
Electronic Unsupported Information: https://tinyurl.com/57txpzca
Note: We weren’t just rejected by JACS, we were excommunicated.