Optical Rotation Calculations Research Articles

The ORP basis set designed for optical rotation calculations

Details of generation of the optical rotation prediction (ORP) basis set developed for accurate optical rotation (OR) calculations are presented. Specific rotation calculations carried out at the density functional theory (DFT) level for model chiral methane molecule, fluorooxirane, methyloxirane, and dimethylmethylenecyclopropane reveal that the ORP set outperforms larger basis sets, among them the aug-cc-pVTZ basis set of Dunning (J. Chem. Phys. 1989, 90, 1007) and the aug-pc-2 basis set of Jensen (J. Chem. Phys. 2002, 117, 9234; J. Chem. Theory Comput. 2008, 4, 719). It is shown to be an attractive choice also in the case of larger systems, namely norbornanone, β-pinene, trans-pinane, and nopinone. The ORP basis set is further used in OR calculations for 24 other systems, and the results are compared to the aug-cc-pVDZ values. Whenever large discrepancies of results are observed, the ORP values are in an excellent agreement with the aug-cc-pVTZ results. The ORP basis set enables accurate specific rotation calculations at a reduced cost and thus can be recommended for routine DFT OR calculations, also for large and conformationally flexible molecules.

Chiroptical properties of ajugol investigated by quantum chemical calculation using time-dependent density functional theory

The chiroptical properties of an iridoid glycoside ajugol were fully investigated by quantum chemical calculations of specific optical rotation at the sodium D line ([α]D value), optical rotatory dispersion (ORD), and electronic circular dichroism (ECD) using time-dependent density functional theory (TDDFT). TDDFT calculations of the [α]D value and ORD of ajugol over the range of 365–633 nm were in good agreement with the experimental data. The predicted ECD spectrum of ajugol was also consistent with the experiment, showing a strong negative Cotton effect (CE) at around 190 nm and a weak positive CE at around 220 nm. Our results unambiguously determined the absolute configuration (AC) of the aglycone part of ajugol as (1S, 5R, 6R, 8S, 9S) and supported the generally accepted AC assignments of iridoid glycosides. Semi-empirical rule for the enol ether chromophore, basis set selection, and effect of glucose group on ECD spectra were also discussed in the case of ajugol.

Circular Dichroism and Optical Rotation of Lactamide and 2-Aminopropanol in Aqueous Solution

The performance of implicit and explicit solvent models (polarizable continuum model (PCM) and microsolvation with positions of water molecules obtained either from molecular dynamics (MD) simulations or quantum mechanical geometry optimization) for calculations of electronic circular dichroism (CD) and optical rotation (OR) is examined for two polar and flexible molecules: lactamide and 2-aminopropanol. The vibrational structure of the CD spectrum is modeled for lactamide. The results are compared with the newly obtained experimental data. The signs of the bands are correctly reproduced using all three methods under investigation and the CAM-B3LYP functional for the CD spectrum of lactamide, but not for 2-aminopropanol. The sign of the calculated optical rotation is correctly predicted by means of PCM, but its magnitude is somewhat underestimated in comparison with experiment for lactamide and overestimated for 2-aminopropanol. To some extent it is rectified by employing explicit hydration. Overall, microsolvation with geometry optimization seems more cost-effective than classical MD, but this is likely to be a consequence of inadequate classical potential and electronic structure model.

Calculation of parity-nonconserving optical rotation in iodine at 1315 nm

We examine the feasibility of a parity non-conserving (PNC) optical rotation experiment for the $^2$P$_{3/2}\rightarrow ^2$P$_{1/2}$ transition of atomic iodine at 1315 nm. The calculated $E1_{\rm PNC}$ to $M1$ amplitude ratio is $R=0.80(16)\times 10^{-8}$. We show that very large PNC rotations (greater than 10 $\mu$rad) are obtained for iodine-atom column densities of $\sim 10^{22}$ cm$^{-2}$, which can be produced by increasing the effective interaction pathlength by a factor of $\sim 10^4$ with a high-finesse optical cavity. The simulated signals indicate that measurement of the nuclear anapole moment is feasible, and that a 1% PNC precision measurement should resolve the inconsistency between previous measurements in Cs and Tl.

Computational Modeling of the Optical Rotation of Amino Acids: An ‘in Silico’ Experiment for Physical Chemistry

A computational experiment that investigates the optical activity of the amino acid valine has been developed for an upper-level undergraduate physical chemistry laboratory course. Hybrid density functional theory calculations were carried out for valine to confirm the rule that adding a strong acid to a solution of an amino acid in the l configuration renders the optical rotation more positive. Correspondingly, if the optical rotation becomes more negative, the amino acid is of the d configuration. The students employed the open-source molecular editor Avogadro to build the molecules, conduct conformer searches, and calculate the energies of the conformers with a molecular mechanics force field. Subsequent geometry optimizations and optical rotation calculations were performed with a quantum chemistry program, using the WebMO graphical interface. The role of the solvent in stabilizing the zwitterionic form of an amino acid was investigated.

Observation of Optical Chemical Shift by Precision Nuclear Spin Optical Rotation Measurements and Calculations

Nuclear spin optical rotation (NSOR) is a recently developed technique for detection of nuclear magnetic resonance via rotation of light polarization, instead of the usual long-range magnetic fields. NSOR signals depend on hyperfine interactions with virtual optical excitations, giving new information about the nuclear chemical environment. We use a multipass optical cell to perform the first precision measurements of NSOR signals for a range of organic liquids and find clear distinction between proton signals for different compounds, in agreement with our earlier theoretical predictions. Detailed first-principles quantum mechanical NSOR calculations are found to be in agreement with the measurements.

Griseusins F and G, Spiro-Naphthoquinones from a Tin Mine Tailings-Derived Alkalophilic Nocardiopsis Species

Griseusins F (1) and G (2), two 2a-hydro-8a-(2-oxopropyl)-substituted spiro-naphthoquinones with a previously undescribed C23 polyketide skeleton, were isolated from a Yunnan tin mine tailings-derived alkalophilic actinomycete, Nocardiopsis sp. YIM DT266. Their complete structure assignments with the absolute stereochemistry were elucidated by spectroscopic data, X-ray crystal diffraction, calculation of optical rotation, and CD spectroscopic analysis. Compounds 1 and 2 exhibited strong cytotoxicity (IC50 0.37-0.82 μM) and antibacterial activity (MIC 0.80-1.65 μg/mL) against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) in vitro.

Absolute Configurations of Unique Harziane Diterpenes from Trichoderma Species

Harzianone (2), a new harziane diterpene, was isolated from an alga-endophytic isolate of Trichoderma longibrachiatum. The structure and absolute configuration of 2 were unambiguously identified by NMR and mass spectrometric methods as well as quantum chemical calculations. The absolute configuration of harziandione (1) was supported by calculation of optical rotation, and the structure of isoharziandione was revised to 1 on the basis of (13)C NMR data comparison and calculation.

Absolute Configuration of Fusarone, a New Azaphilone from the Endophytic Fungus Fusarium sp. Isolated from Melia azedarach, and of Related Azaphilones

A new azaphilone derivative, named fusarone (1), has been isolated from the ethyl acetate soluble extract of the fermentation broth of an endophytic fungus, Fusarium sp. LN-12, isolated from the leaves of Melia azedarach Linn. The structure of the new compound was established on the basis of extensive spectroscopic analysis, including 1D-NMR and 2D-NMR ((1) H-(1)H COSY, TOCSY, HSQC, HMBC, and NOESY) experiments. The absolute configurations of fusarone (1) and of a second related azaphilone were determined by means of electronic circular dichroism spectroscopy and optical rotation calculations.

The optical activity of carvone: A theoretical and experimental investigation

The optical rotatory dispersion (ORD) and circular dichroism of the conformationally flexible carvone molecule has been investigated in 17 solvents and compared with results from calculations for the "free" (gas phase) molecule. The G3 method was used to determine the relative energies of the six conformers. The optical rotation of (R)-(-)-carvone at 589 nm was calculated using coupled cluster and density functional methods, including temperature-dependent vibrational corrections. Vibrational corrections are significant and are primarily associated with normal modes involving the stereogenic carbon atom and the carbonyl group, whose n → π∗ excitation plays a significant role in the chiroptical response of carvone. Without the inclusion of vibrational corrections the optical rotation calculated with CCSD and DFT has the opposite sign of experimental data. Calculations of optical rotation performed in solution using the polarizable continuum model were also opposite in sign when compared to that of the experiment.

Lipase‐Catalyzed Kinetic Resolution of 2‐Phenylethanol Derivatives and Chiral Oxa‐Pictet–Spengler Reaction as the Key Steps in the Synthesis of Enantiomerically Pure Tricyclic Amines

AbstractA series of 5,6,7,8,9,10‐hexahydro‐5,9‐epoxybenzocycloocten‐6‐amines have been synthesized and pharmacologically evaluated in receptor binding studies (σ1, σ2, NMDA, κ, and μ receptors). The first key step of the synthesis was a chiral oxa‐Pictet–Spengler reaction with enantiomerically pure 2‐phenylethanol derivatives (S)‐ and (R)‐14. After transformation of the dimethylamide 18 into the ester 19, the tricyclic system 20 was established by Dieckmann cyclization reaction. Finally, amino moieties were introduced diastereoselectively into the 6‐position by reductive amination and SN2 reaction. The enantiomerically pure building blocks (S)‐14 (>99.0 % ee) and (R)‐14 (98.4 % ee) were synthesized by enantioselective acetylation of racemic alcohol 14 catalyzed by Pseudomonas fluorescens lipase and enantioselective hydrolysis of racemic acetate 16 catalyzed by Candida rugosa lipase. The absolute configurations were determined by theoretical calculations of the specific optical rotation and CD spectra, as well as by X‐ray crystal structure analysis of (S,S,S)‐25 by the three‐beam interference method. Although enantiomerically pure dimethylamines (S,R,S)‐ and (R,S,R)‐29 with an axial amino moiety showed low‐to‐moderate affinity towards σ1 and σ2 receptors, a promising σ2 affinity (Ki = 2.9 μM) was found for (S,S,S)‐24 with an equatorially oriented dimethylamino group.

A pair of tirucallane C27-triterpenoid cyclopentenone epimers from the stem barks of Aphanamixis grandifolia

Two novel tirucallane C27-triterpenoid epimers, aphagranins A (1) and B (2), featuring an unprecedented enolized cyclopentenone presented in the side-chain at C-17, were isolated from the stem barks of Aphanamixis grandifolia. Extensive spectroscopic analyses helped the establishment of the structures of the two isolates, whose absolute configurations were determined using density functional theory (DFT) calculations of optical rotation, and electronic circular dichroism (ECD). Remarkable discrepancies in the inhibitory activities against the growth of six lines of human cancer cells (MCF-7, A549, HepG2, Bel-7402, SGC-7901, and BGC-823) were found for the two epimers: with IC50 less than 10μM, aphagranin A exhibited much stronger antiproliferative activity than aphagranin B, showing no such activities with IC50 over 20μM.

Calculations of optical rotation: Influence of molecular structure

Ab initio Hartree-Fock (HF) method and Density Functional Theory (DFT) were used to calculate the optical rotation of 26 chiral compounds. The effects of theory and basis sets used for calculation, solvents influence on the geometry and values of calculated optical rotation were all discussed. The polarizable continuum model, included in the calculation, did not improve the accuracy effectively, but it was superior to ?s. Optical rotation of five or sixmembered of cyclic compound has been calculated and 17 pyrrolidine or piperidine derivatives which were calculated by HF and DFT methods gave acceptable predictions. The nitrogen atom affects the calculation results dramatically, and it is necessary in the molecular structure in order to get an accurate computation result. Namely, when the nitrogen atom was substituted by oxygen atom in the ring, the calculation result deteriorated.

Fully Relativistic Calculations of Faraday and Nuclear Spin-Induced Optical Rotation in Xenon.

Nuclear spin-induced optical rotation (NSOR) arising from the Faraday effect may constitute an advantageous novel method for the detection of nuclear magnetization. We present first-principles nonrelativistic and relativistic, two- and four-component, basis-set limit calculations of this phenomenon for xenon. It is observed that only by utilization of relativistic methods may one qualitatively reproduce experimental liquid-state NSOR data. Relativistic effects lower the results by 50% as compared to nonrelativistic values. Indeed, relativistic Hartree-Fock calculations at the four-component or exact two-component (X2C) level account for the discrepancy between experimental results and earlier nonrelativistic theory. The nuclear magnetic shielding constant of traditional nuclear magnetic resonance as well as the Verdet constant parametrizing optical rotation due to an external magnetic field were also calculated. A comparison between results obtained using Hartree-Fock and density-functional theory methods at relativistic and nonrelativistic levels, as well as coupled cluster methods at the nonrelativistic level, was carried out. Completeness-optimized basis sets were employed throughout, for the first time in fully relativistic calculations. Full relativity decreases the Verdet constant by 4%. X2C theory decreases the absolute value of NSOR by 10-20% as compared to the four-component data, while for Verdet constants, the results are only slightly smaller than the fully relativistic values. For both properties, two-component calculations decrease the computational time by roughly 90%. Density-functional methods yield substantially larger values of NSOR than the Hartree-Fock theory or experiments. Intermolecular interactions are found to decrease NSOR and, hence, compensate for the electron correlation effect.

Optical Rotation Calculated with Time-Dependent Density Functional Theory: The OR45 Benchmark

Time-dependent density functional theory (TDDFT) computations are performed for 42 organic molecules and three transition metal complexes, with experimental molar optical rotations ranging from 2 to 2 × 10(4) deg cm(2) dmol(-1). The performances of the global hybrid functionals B3LYP, PBE0, and BHLYP, and of the range-separated functionals CAM-B3LYP and LC-PBE0 (the latter being fully long-range corrected), are investigated. The performance of different basis sets is studied. When compared to liquid-phase experimental data, the range-separated functionals do, on average, not perform better than B3LYP and PBE0. Median relative deviations between calculations and experiment range from 25 to 29%. A basis set recently proposed for optical rotation calculations (LPol-ds) on average does not give improved results compared to aug-cc-pVDZ in TDDFT calculations with B3LYP. Individual cases are discussed in some detail, among them norbornenone for which the LC-PBE0 functional produced an optical rotation that is close to available data from coupled-cluster calculations, but significantly smaller in magnitude than the liquid-phase experimental value. Range-separated functionals and BHLYP perform well for helicenes and helicene derivatives. Metal complexes pose a challenge to first-principles calculations of optical rotation.

On the Route of the Determination of Monosaccharides Conformations

Many theoretical studies on carbohydrates have been published in the last century. Building on these developments, a procedure is presented to select stable conformations of monosaccharides in aqueous solution from samplings on potential energy surfaces (PES) obtained from quantum mechanics. Considerations regarding the property chosen to validate conformational samplings are also presented. The conformations found for D-xylopyranose present an optical rotation value of +20.35°, which coincides with the experimental value (+18.8°). Keywords: Monosaccharide conformations, monosaccharide potential energy surface, optical rotation calculations for carbohydrate, carbohydrate conformations, optical rotation, D-xylopyranose

Basis set convergence on optical rotation DFT calculations

Recently, a hierarchical sequence of augmented basis sets of double, triple, and quadruple zeta valence qualities plus polarization functions for the atoms from H to Ar was generated. At the B3LYP, PBE1PBE, M06, and M06-2X levels, we report a systematic study of Gaussian basis set convergence on frequency dependent optical rotation ([ α] ω) calculations of thirteen rigid chiral molecules at their equilibrium geometries. By direct calculations or by fitting the directly calculated values through one extrapolation scheme, estimates of complete basis set (CBS) limits were obtained. These CBS limits can be used as reference values to calibrate further DFT calculations.

Naphthospironone A: An Unprecedented and Highly Functionalized Polycyclic Metabolite from an Alkaline Mine Waste Extremophile

Bring in the new: Naphthospironone A (1), a novel polycyclic metabolite with an unprecedented spiro[bicyclo[3.2.1]octene-pyran]dione ring system, was isolated from alkalophilic Nocardiopsis sp. (YIM DT266). Its complete structural assignment with the absolute stereochemistry was elucidated by spectroscopic data, X-ray crystal diffraction, and calculation of optical rotation by using DFT methods. Naphthospironone A exhibited moderate cytotoxic and antibiotic bioactivities.

Absolute Configuration Assignment of Norcamphor-Derived Furyl Hydroperoxide Using Density Functional Theory Calculations of Optical Rotation and Vibrational Circular Dichroism

Density functional theory (DFT) calculations of sodium d line specific rotation and of vibrational circular dichroism (VCD) have been used to assign the absolute configuration of a recently prepared (1S,4R)-norcamphor-derived furyl hydroperoxide, (+)-3, introduced as a stereoselective oxidant. Both approaches give the same absolute configuration to the newly generated stereogenic carbon at position 2, i.e., (1S,2S,4R)-(+)-3, thus providing a confident assignment in a case made difficult by the large conformational flexibility and the small difference between the computed optical rotations of the two possible diastereoisomers. Although the computed IR absorption spectra of (1S,2S,4R)-3 and (1S,2R,4R)-3 are practically indistinguishable, a number of significant differences in the VCD spectra of these two nonmirror-image isomers can be observed, which allows the structural identification of the synthesized compound. This is clearly shown here for the first time.

Optical Faraday rotation

Three calculations of optical Faraday rotation are presented in which a linearly polarized field is incident on a medium of harmonic oscillators in the presence of a longitudinal magnetic field. The rotation of the plane of polarization of the field is evaluated using classical oscillators and the Lorentz force equation, quantum oscillators and the Heisenberg equations of motion, and quantum oscillators and a Schrödinger equation approach. It is shown that a simple argument, based on the assumption that a circularly polarized field drives either Δm=1 or Δm=−1 transitions on absorption (m is the magnetic quantum number), leads to an incorrect result for the Verdet constant.