Computational Chemistry to the Rescue: Modern Toolboxes for the Assignment of Complex Molecules by GIAO NMR Calculations

The calculations of NMR properties of molecules using quantum chemical methods have deeply impacted several branches of organic chemistry. They are particularly important in structural or stereochemical assignments of organic compounds, with implications in total synthesis, stereoselective reactions, and natural products chemistry. In studying the evolution of the strategies developed to support (or reject) a structural proposal, it becomes clear that the most effective and accurate ones involve sophisticated procedures to correlate experimental and computational data. Owing to their relatively high mathematical complexity, such calculations (CP3, DP4, ANN‐PRA) are often carried out using additional computational resources provided by the authors (such as applets or Excel files). This Minireview will cover the state‐of‐the‐art of these toolboxes in the assignment of organic molecules, including mathematical definitions, updates, and discussion of relevant examples.     

Microwave-assisted regioselective cycloaddition reactions between 9-substituted anthracenes and levoglucosenone

The cycloaddition reactions of 9-substituted anthracenes and levoglucosenone were investigated under microwave irradiation and conventional heating conditions. Considering time, yields, and regioselectivity, microwave technology has proven to be an ideal tool to achieve this chemical transformation. [reaction: see text].     

Complex copper(II) fluorides. XV. The Ternary System BaF2?CuF2?ScF3

The liquid-solid phase diagram of the binary system BaF₂? ScF₃ is established by D.T.A. and radiocrystallography. Three fluorides are disclosed: Ba₃Sc₂F₁₂, Ba₅Sc₃F₁₉ and a cubic high temperature phase Ba_1?xSc_xF_2+x (x = 0.17), the structure of which derives from that of BaF₂. A solid solution between BaF₂ and ScF₃ is also evidenced at high temperature. The ternary system BaF₂? CuF₂? ScF₃ is investigated by radiocrystallography and an isothermal section at 670°C is given. It shows the existence of four phases: a complex quaternary fluoride Ba₁₀Cu₁₂ScF₄₇, two “polytypic” phases the structure of which derives from that of BaCuF₄ and a tetragonal solid solution Ba₅Sc_3?xCu_xF_19?x with 0 ≤ x ≤ 1.     

Synthesis of dihydroxylated prolines and iminocyclitols from five-membered endocyclic enecarbamates. Total synthesis of the potent glycosidase inhibitor (2R,3R,4R,5R)-2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP)

cis- and trans-3,4-Dihydroxylated prolines and the iminocyclitol 1,4-dideoxy-1,4-imino ribitol were synthesized employing a strategy involving the Heck arylation of five-membered endocyclic enecarbamates with aryldiazonium salts followed by oxidative cleavage of the electron-rich aromatic ring. The total synthesis of the potent α- and β-glucosidase inhibitor (2R,3R,4R,5R)-2,5-hydroxymethyl-3,4-dihydroxypyrrolidine (DMDP) was also achieved by the same strategy in ten steps from a chiral five-membered enecarbamate in 12% overall yield.     

The Crystal Structure of Ba3Cu2Al2F16: a Relative of Ba4Cu2Al3F21

Ba₃Cu₂Al₂F₁₆ is monoclinic: a = 7.334(1)Å, b = 5.320(2)Å, c = 16.022(1)Å, β = 96.34(1)°, Z = 2. Its crystal structure was solved in the space group P2₁ (No. 4) from synchrotron X‐ray single crystal data using 2685 unique reflections (2639 with F_o/σ(F_o) > 4). The final R factor is 0.044. The structure consists of a succession along the c‐axis of the cell of three layers of two different kinds of sheets developing in the (a, b) plane. The first one, formulated [(AlF₅)₂]_∞^4— and hereafter named A, is built up from infinite cis‐chains of aluminium‐fluorine octahedra [AlF₆], linked by two vertices and distanced by a. The second one, formulated [Cu₂AlF₁₁]_∞^4— and named B, is bidimensional. It is constituted of distorted copper‐fluorine octahedra [CuF₆], linked by edges, which form infinite chains interconnected by three vertices of isolated [AlF₆] octahedra. The stacking sequence of the sheets is (A, B, B)_∞. The barium ions, 12‐coordinated, are inserted between the sheets. The crystal structure of Ba₃Cu₂Al₂F₁₆ is closely related to that of Ba₄Cu₂Al₃F₂₁. Only the proportion and the stacking sequence of the two kinds of sheets in the c‐direction differ, according to two different compositions and two different symmetries.     

Regulating the size and stabilization of lipid raft-like domains and using calcium ions as their probe

We apply a means to probe, stabilize, and control the size of lipid raft-like domains in vitro. In biomembranes the size of lipid rafts is ca. 10-30 nm. In vitro, mixing saturated and unsaturated lipids results in microdomains, which are unstable and coalesce. This inconsistency is puzzling. It has been hypothesized that biological line-active surfactants reduce the line tension between saturated and unsaturated lipids and stabilize small domains in vivo. Using solution X-ray scattering, we studied the structure of binary and ternary lipid mixtures in the presence of calcium ions. Three lipids were used: saturated, unsaturated, and a hybrid (1-saturated-2-unsaturated) lipid that is predominant in the phospholipids of cellular membranes. Only membranes composed of the saturated lipid can adsorb calcium ions, become charged, and therefore considerably swell. The selective calcium affinity was used to show that binary mixtures, containing the saturated lipid, phase separated into large-scale domains. Our data suggests that by introducing the hybrid lipid to a mixture of the saturated and unsaturated lipids, the size of the domains decreased with the concentration of the hybrid lipid, until the three lipids could completely mix. We attribute this behavior to the tendency of the hybrid lipid to act as a line-active cosurfactant that can easily reside at the interface between the saturated and the unsaturated lipids and reduce the line tension between them. These findings are consistent with a recent theory and provide insight into the self-organization of lipid rafts, their stabilization, and size regulation in biomembranes.     

Application of the multi-standard methodology for calculating 1H NMR chemical shifts

Gauge including atomic orbitals (GIAO) (1)H NMR chemical shift calculations have been performed for 66 organic compounds at 72 different levels of theory using the multi-standard approach (MSTD) previously developed for (13)C NMR. This straightforward computational technique involves the combination of methanol and benzene as standards. The studied methodology has been shown to predict (1)H NMR chemical shifts efficiently at different levels of theory.