Deuterium isotope effects on noncovalent interactions between molecules

Wade, David

doi:10.1016/s0009-2797(98)00097-0

Cited by 173 publications

(161 citation statements)

References 59 publications

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“…Ligand-receptor interactions can be both attractive and repulsive, involving hydrogen bonding, van der Waals, cation-π, π-π, ion-ion, dipoledipole, steric, and hydrophobic interactions with the receptor, with water channels and bridging water molecules mediating hydrogen bonds, as well as metal-ion coordination, as we have recently demonstrated in the latter case (15,16). Therefore, molecular shape can be considered a "straw-man" alternative to the vibration theory when describing the differing affinities of ligands bound to GPCRs (17,18), including isotopomers (19,20). Some of these attractive and repulsive interactions were identified in 1940 by Pauling and Delbrück (21), who note that interacting biomolecules "must have complementary surfaces, like die and coin, and also a complementary distribution of active groups."…”

Section: Significancementioning

confidence: 99%

Implausibility of the vibrational theory of olfaction

Block

Jang

Matsunami

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

115

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The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/ deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. Here, we find no evidence for such differentiation at the molecular level. In fact, we find that the human musk-recognizing receptor, OR5AN1, identified using a heterologous OR expression system and robustly responding to cyclopentadecanone and muscone, fails to distinguish isotopomers of these compounds in vitro. Furthermore, the mouse (methylthio)methanethiol-recognizing receptor, MOR244-3, as well as other selected human and mouse ORs, responded similarly to normal, deuterated, and 13 C isotopomers of their respective ligands, paralleling our results with the musk receptor OR5AN1. These findings suggest that the proposed vibration theory does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other ORs examined. Also, contrary to the vibration theory predictions, muscone-d 30 lacks the 1,380-to 1,550-cm −1 IR bands claimed to be essential for musk odor. Furthermore, our theoretical analysis shows that the proposed electron transfer mechanism of the vibrational frequencies of odorants could be easily suppressed by quantum effects of nonodorant molecular vibrational modes. These and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.olfaction | isotopomers | cyclopentadecanone | muscone | electron transfer I n 1870, the British physician William Ogle wrote: "As in the eye and the ear the sensory impression is known to result not from the contact of material particles given off by the object seen or heard, but from waves or undulations of the ether or the air, one cannot but suspect that the same may be true in the remaining sense, and that the undulatory theory of smell. . . [may be] the true one" (1, 2). Of the 29 different "theories of odour" listed in the 1967 edition of The Chemical Senses (3), nine associate odor with vibrations, particularly those theories championed by Dyson (4, 5) and Wright (6-8). However, the premise that olfaction involves detection of vibrational frequencies of odorants remains highly speculative because neither the structures of the odorant receptors (ORs) nor the binding sites or the activation mechanisms triggered upon odorant binding to ORs have been established. In 1996-1997, Turin (9-12) elaborated on the undulatory theory of smell, as considered in more detail below, and suggested that a mechanism analogous to inelastic electron tunneling spectroscopy (13) may be involved, where tunneling electrons in the receptor probe the vibrational frequencies of odorants. In 2013, Gane et al. (14) In judging the plausibility...

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Section: Significancementioning

confidence: 99%

Implausibility of the vibrational theory of olfaction

Block

Jang

Matsunami

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

115

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“…The SIE involves the structure of water and macromolecules. On the other hand, the DIE involves the ability of D 2 8,32) . Although it is not easy to distinguish between the SIE and DIE, long-term effects are probably due to the DIE and short-term effects to the SIE.…”

Section: Original Articlementioning

confidence: 99%

Effects of Deuterium Oxide on Streptococcus mutans and Pseudomonas aeruginosa

Hirai

Tomida

Kikuchi

et al. 2010

Bull. Tokyo Dent. Coll.

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A complex aggregation of microorganisms growing on a solid substrate is termed a biofilm and is considered to be an etiological agents. Pseudomonas aeruginosa and Streptococcus mutans are representative bacteria in such biofilms. It is well known that deuterium oxide (D 2 O) causes toxic effects on a number of biological systems. We investigated the effects of D 2 O on growth and biofilm formation of P. aeruginosa and S. mutans. These bacteria were incubated in medium containing D 2 O (100%, 75% or 0%) at 37°C for 24hr, 48 hr or 72hr. Growth of P. aeruginosa was inhibited by D 2 O within the first 48hr. However, after 72 hr, growth rate was seen to increase in the D 2 O-containing medium compared with in medium without D 2 O. In contrast, the growth of S. mutans in the D 2 O medium was inhibited within 72hr. The biofilm formation of P. aeruginosa was increased in the D 2 O medium. Biofilm formation of S. mutans in the D 2 O medium increased compared with in the medium without D 2 O, but this increase was only temporary in the case of P. aeruginosa. Compared to biofilm formation in 0% D 2 O medium marked as 100%, the biofilm formation rate of S. mutans in 75% D 2 O medium was 143% at 24hr, 146% at 48 hr and 130% at 72 hr. In other D 2 O concentration media biofilm formation was lower. In 100% D 2 O medium, biofilm formation rate decreased from 114% at 24hr to 56% at 72hr. The biofilm formation rate of P. aeruginosa in 100% D 2 O medium was 172% at 24hr, but decreased to 88% at 72hr. Biofilm formation of P. aeruginosa in 75% and 0% D 2 O media showed no significant difference. We consider that these results were due to stress or alteration in bacterial metabolisms.

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“…Deuterium isotope effects in the absence of covalent bond breaking and formation have been extensively documented (42). Noncovalent deuterium isotope effects are primarily attributed to the shorter bond length of C-D versus C-H as well as to the changes in molecular volume and polarity or polarizability.…”

Section: Oxidation Of Aa By Peroxide-induced Asa-pghs-2 Radical(s)-mentioning

confidence: 99%

Structural Characterization of Arachidonyl Radicals Formed by Aspirin-treated Prostaglandin H Synthase-2

Tsai¹,

Palmer²,

Wu³

et al. 2002

Journal of Biological Chemistry

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Peroxide-generated tyrosyl radicals in both prostaglandin H synthase (PGHS) isozymes have been demonstrated to couple the peroxidase and cyclooxygenase activities by serving as the immediate oxidant for arachidonic acid (AA) in cyclooxygenase catalysis. Acetylation of Ser-530 of PGHS-1 by aspirin abolishes all oxygenase activity and transforms the peroxide-induced tyrosyl radical from a functional 33-35-gauss (G) wide doublet/wide singlet to a 26-G narrow singlet unable to oxidize AA. In contrast, aspirin-treated PGHS-2 (ASA-PGHS-2) no longer forms prostaglandins but retains oxygenase activity forming 11(R)-and 15(R)-hydroperoxyeicosatetraenoic acid and also retains the EPR line-shape of the native peroxide-induced 29 -30-G wide singlet radical. To evaluate the functional role of the wide singlet radical in ASA-PGHS-2, we have examined the ability of this radical to oxidize AA in singleturnover EPR studies. Anaerobic addition of AA to ASA-PGHS-2 immediately after formation of the wide singlet radical generated either a 7-line EPR signal similar to the pentadienyl AA radical obtained in native PGHS-2 or a 26 -28-G singlet radical. These EPR signals could be accounted for by a pentadienyl radical and a strained allyl radical, respectively. Experiments using 11d-AA, 13(R)d-AA, 15d-AA, 13,15d 2 -AA, and octadeuterated AA (d 8 -AA) confirmed that the unpaired electron in the pentadienyl radical is delocalized over C11, C13, and C15. A 6-line EPR radical was observed when 16d 2 -AA was used, indicating only one strongly interacting C16 hydrogen. These results support a functional role for peroxide-generated tyrosyl radicals in lipoxygenase catalysis by ASA-PGHS-2 and also indicate that the AA radical in ASA-PGHS-2 is more constrained than the corresponding radical in native PGHS-2.

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Deuterium isotope effects on noncovalent interactions between molecules

Cited by 173 publications

References 59 publications

Implausibility of the vibrational theory of olfaction

Implausibility of the vibrational theory of olfaction

Effects of Deuterium Oxide on Streptococcus mutans and Pseudomonas aeruginosa

Structural Characterization of Arachidonyl Radicals Formed by Aspirin-treated Prostaglandin H Synthase-2

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