The observed 1° isotope effect on 2° KIEs in H-transfer reactions has recently been explained on the basis of a H-tunneling mechanism that uses the concept that the tunneling of a heavier isotope requires a shorter donor-acceptor distance (DAD) than that of a lighter isotope. The shorter DAD in D-tunneling, as compared to H-tunneling, could bring about significant spatial crowding effect that stiffens the 2° H/D vibrations, thus decreasing the 2° KIE. This leads to a new physical organic research direction that examines how structure affects the 1° isotope dependence of 2° KIEs and how this dependence provides information about the structure of the tunneling ready states (TRSs). The hypothesis is that H- and D-tunneling have TRS structures which have different DADs, and pronounced 1° isotope effect on 2° KIEs should be observed in tunneling systems that are sterically hindered. This paper investigates the hypothesis by determining the 1° isotope effect on α- and β-2° KIEs for hydride transfer reactions from various hydride donors to different carbocationic hydride acceptors in solution. The systems were designed to include the interactions of the steric groups and the targeted 2° H/D's in the TRSs. The results substantiate our hypothesis, and they are not consistent with the traditional model of H-tunneling and 1°/2° H coupled motions that has been widely used to explain the 1° isotope dependence of 2° KIEs in the enzyme-catalyzed H-transfer reactions. The behaviors of the 1° isotope dependence of 2° KIEs in solution are compared to those with alcohol dehydrogenases, and sources of the observed "puzzling" 2° KIE behaviors in these enzymes are discussed using the concept of the isotopically different TRS conformations.

Creatine is recognized as a dietary staple among athletes, with two supplement formulations currently available on the United States market: creatine monohydrate and creatine hydrochloride. Creatine monohydrate has relatively low aqueous solubility, which hampers its ease of preparation by consumers. Creatine hydrochloride has excellent aqueous solubility; however, it exhibits a strong acidic taste with potentially harmful effects on dental health. Herein, we report a mechanochemical synthesis of a 1:1 coamorphous formulation of creatine and citric acid, a-CCA. Milling of anhydrous creatine and anhydrous citric acid yielded a-CCA, which was found to be structurally stable under dry conditions. Upon exposure to humid air, a-CCA rapidly converted into a 1:1 cocrystalline formulation, c-CCA. Correspondingly, milling of creatine and citric acid, with at least one source present as a monohydrate, resulted in direct mechanosynthesis of the cocrystal. The crystal structure was solved and refined from powder X-ray diffraction data, and the obtained structure solution was evaluated by energy minimization calculations. Close inspection of the hydrogen-bonding network revealed the presence of creatine in zwitterionic form and of citric acid as a neutral molecule. Additionally, the coamorphous solid and the cocrystal were studied by infrared spectroscopy, differential scanning calorimetry, and thermogravimetry. The aqueous solubility of the cocrystal (32.0(8) g/L) was determined to be ∼2.5× higher compared to that of commercial creatine monohydrate (13.3(6) g/L). The cocrystal formulation was determined to be ∼10× less acidic compared to commercial creatine hydrochloride. The simple, efficient, and scalable method of preparation, the phase-purity and high degree of crystallinity under ambient conditions, and the increased solubility (compared to the creatine monohydrate) and decreased acidity (compared to creatine hydrochloride) render the 1:1 creatine:citric acid cocrystal an improved and potentially marketable creatine supplement formulation.

Ethylene bis­(dithiocarbamates) (EBDTCs) have been used as staple fungicides for over 75 years. The first industrially manufactured EBDTC was zineb, zinc ethylene bis­(dithiocarbamate), marketed under the trade name Dithane. Even though zineb has been used as a fungicide since the 1940s, its crystal structure has remained unknown. Herein, we describe the crystal structure of zineb (triclinic crystal system, space group P1̅, a = 7.5094(9) Å, b = 9.4356(9) Å, c = 7.4120(7) Å, α = 107.945(8)°, β = 100.989(7)°, γ = 105.365(8)°, V = 460.07(10) Å3). The inorganic fragment of the structure consists of two Zn2+ cations, coordinated by the thiocarbamate groups. There are four Zn–S bonds with lengths in the range of 2.325–2.426 Å, and one rather long Zn–S contact of 2.925(8) Å. Inorganic fragments are linked by organic EBDTC ligands to form extended, polymeric layers. The layers are packed in an ABAB manner, related by the inversion symmetry and held together by a hydrogen bonding network. In this article, in addition to describing the crystal structure, we correlate the structural features with the vibrational spectroscopic and thermal characteristics of zineb, and we provide a short summary of the major developments of fungicides in the 20th century.

Here we report the phase diagram of acetonitrile and benzene with the focus on a 1 : 3 acetonitrile : benzene cocrystal relevant to mineralogy of Titan, Saturn's moon.