Molecular Structure Determination Research Articles

Enhancement of the chiroptical response of α-amino acids via N-substitution for molecular structure determination using vibrational circular dichroism.

The chiroptical response in the form of vibrational circular dichroism (VCD) in the midinfrared region is found to be enhanced when a hydrogen of amino group of l-tryptophan is substituted with acetyl, acryloyl, or maleyl group. The order of preference for VCD enhancement is found to be acryloyl > acetyl > maleyl group. The resulting experimental VCD spectra are also found to be satisfactorily reproduced by the quantum mechanical (QM) predicted spectra. The QM predicted spectra were simulated using the conformer populations, (a) predicted by Gibbs energies and (b) optimized to maximize the similarity between experimental and predicted VCD spectra. It is found that the conformer populations predicted by Gibbs energies do not yield the maximum possible similarity between experimental and the QM predicted spectra. This work identifies the N-substitution of α-amino acids and determining the conformer populations that best reproduce the experimental spectra as two new approaches for molecular structure determination.

Determination of Complex Small-Molecule Structures Using Molecular Alignment Simulation.

Correct structural assignment of small molecules and natural products is critical for drug discovery and organic chemistry. Anisotropy‐based NMR spectroscopy is a powerful tool for the structural assignment of organic molecules, but it relies on the utilization of a medium that disrupts the isotropic motion of molecules in organic solvents. Here, we establish a quantitative correlation between the atomic structure of the alignment medium, the molecular structure of the small molecule, and molecule‐specific anisotropic NMR parameters. The quantitative correlation uses an accurate three‐dimensional molecular alignment model that predicts residual dipolar couplings of small molecules aligned by poly(γ‐benzyl‐l‐glutamate). The technique facilitates reliable determination of the correct stereoisomer and enables unequivocal, rapid determination of complex molecular structures from extremely sparse NMR data.

Structural Analysis of Nuclear Spin Clusters via 2D Nanoscale Nuclear Magnetic Resonance Spectroscopy

Abstract2D nuclear magnetic resonance (NMR) is essential in molecular structure determination. The nitrogen vacancy (NV) center in diamond is proposed and developed as an outstanding quantum sensor to realize NMR in nanoscale. In this work, a scheme for 2D nanoscale NMR spectroscopy is developed based on quantum controls on an NV center. A proof‐of‐principle experiment on a target of two coupled nuclear spins in diamond is carried out. A correlation spectroscopy (COSY) like sequence is used to acquire the data on time domain, which is then converted to frequency domain with the fast Fourier transform. With the 2D NMR spectrum, the structure and location of the set of nuclear spin are resolved. This work marks a fundamental step toward resolving the structure of a single molecule.

Квантово-химическое определение молекулярной структуры 1,2,4-триазола и расчет его инфракрасного спектра

Молекулярную структуру 1,2,4-триазола рассчитали методом функционала электронной плотности в приближении B3LYP/6-31G с использованием комплекса программ Gaussian. Рассчитанные длины связей и валентные углы удовлетворительно совпадают с их экспериментальными значениями. Результаты расчета показали, что триазол имеет плоскую структуру. Рассчитаны частоты нормальных колебаний триазола и проведено отнесение этих нормальных колебаний. Вычислены интенсивности полос поглощений и построен ИК спектр триазола. При сравнении теоретический спектр качественно воспроизводит экспериментальный спектр.

Crystallography before the Discovery of X-Ray Diffraction

Abstract This paper presents a brief description of the prevailing ideas and hypothesis about the nature of matter from antiquity to the end of XIX century. It shows how gradually, since the Hauy proposal of the existence of the unit cell, the crystal lattice and symmetry and subsequent derivation of the 14 crystal classes by the French Physicist A. Bravais, the 32 point groups by the German mathematician A. Shoenfliess and the 230 space groups independently deduced by the Russian mathematician E. S. Fedorov and A. Shoenflies confirmed the atomic theory suggested by the Greek philosopher Democritus. These empirical and theoretical findings, conducted by several scientists, are one of the most brilliant theoretical predictions of all time in Science, fully confirmed after von Laue discovery of X-ray diffraction by crystals in 1912 and its application on the determination of molecular and crystalline structure by the English physicists W. H. Bragg (1862-1942) and his son W. L. Bragg (1890-1971).

Impact of infra red spectroscopy in quantitative estimation: An update

Various analytical techniques are available nowadays to quantify a substance in a sample. These techniques are based on the quantitative performance of suitable chemical reaction, the characteristic movement of a substance through a defined medium under controlled conditions, electrical measurement, and the measurement of some spectroscopic properties of the compound. Fourier transform infrared (FTIR) spectroscopic imaging with infrared array detectors has recently emerged as a powerful materials characterization tool. IR spectroscopy is a significant technique which utilizes electromagnetic radiations in the infrared region for the determination and identification of molecular structure. Infrared (IR) spectroscopy is one of the oldest and well recognized experimental techniques for the examination of proteins, food stuffs, dyes, pharmaceutical formulations, etc. In this paper, authors have compiled various quantitative applications if infrared spectroscopy for determination of pharmaceutical suspension formulations, determination of lipids and fatty acids in food stuffs, determination of dyes, etc.

Intermetallic transfer of unsymmetrical borylene fragments: isolation of the second early-transition-metal terminal borylene complex and other rare species.

Transition metal borylene complexes of the type [(OC)5M[double bond, length as m-dash]BN(SiMe3)(tBu)] (M = Cr, Mo, W) have been synthesised by salt elimination of the corresponding dibromoborane and the dianionic metallates Na2[M(CO)5]. The borylene complexes have been characterised by multinuclear solution-state NMR spectroscopy and solid-state molecular structure determination. The group 6 borylene complexes can be used to effectively transfer the borylene ligand to other transition metal complexes by replacing one or two carbonyl ligands upon irradiation of the reaction mixture with UV light. This borylene transfer reaction led to the formation of new terminal and bridging borylene complexes which cannot be formed by the corresponding salt elimination reactions, including a rare example of a bis(terminal borylene) complex and only the second reported terminal borylene complex of an early transition metal (vanadium).

Biochemical and Structural Characterization of OXA-405, an OXA-48 Variant with Extended-Spectrum β-Lactamase Activity.

OXA-48-producing Enterobacterales have now widely disseminated globally. A sign of their extensive spread is the identification of an increasing number of OXA-48 variants. Among them, three are particularly interesting, OXA-163, OXA-247 and OXA-405, since they have lost carbapenem activities and gained expanded-spectrum cephalosporin hydrolytic activity subsequent to a four amino-acid (AA) deletion in the β5–β6 loop. We investigated the mechanisms responsible for substrate specificity of OXA-405. Kinetic parameters confirmed that OXA-405 has a hydrolytic profile compatible with an ESBL (hydrolysis of expanded spectrum cephalosporins and susceptibility to class A inhibitors). Molecular modeling techniques and 3D structure determination show that the overall dimeric structure of OXA-405 is very similar to that of OXA-48, except for the β5–β6 loop, which is shorter for OXA-405, suggesting that the length of the β5–β6 loop is critical for substrate specificity. Covalent docking with selected substrates and molecular dynamics simulations evidenced the structural changes induced by substrate binding, as well as the distribution of water molecules in the active site and their role in substrate hydrolysis. All this data may represent the structural basis for the design of new and efficient class D inhibitors.

Architecture of the Escherichia coli nucleoid.

How genomes are organized within cells and how the 3D architecture of a genome influences cellular functions are significant questions in biology. A bacterial genomic DNA resides inside cells in a highly condensed and functionally organized form called nucleoid (nucleus-like structure without a nuclear membrane). The Escherichia coli chromosome or nucleoid is composed of the genomic DNA, RNA, and protein. The nucleoid forms by condensation and functional arrangement of a single chromosomal DNA with the help of chromosomal architectural proteins and RNA molecules as well as DNA supercoiling. Although a high-resolution structure of a bacterial nucleoid is yet to come, five decades of research has established the following salient features of the E. coli nucleoid elaborated below: 1) The chromosomal DNA is on the average a negatively supercoiled molecule that is folded as plectonemic loops, which are confined into many independent topological domains due to supercoiling diffusion barriers; 2) The loops spatially organize into megabase size regions called macrodomains, which are defined by more frequent physical interactions among DNA sites within the same macrodomain than between different macrodomains; 3) The condensed and spatially organized DNA takes the form of a helical ellipsoid radially confined in the cell; and 4) The DNA in the chromosome appears to have a condition-dependent 3-D structure that is linked to gene expression so that the nucleoid architecture and gene transcription are tightly interdependent, influencing each other reciprocally. Current advents of high-resolution microscopy, single-molecule analysis and molecular structure determination of the components are expected to reveal the total structure and function of the bacterial nucleoid.

Spectroscopic investigation of some electron withdrawing groups substituted TTF donor.

The structure optimization and spectroscopic properties for some derivatives of tetrathiafulvalene in both the neutral and ionized forms have been studied. The electron withdrawing groups like -CN, -CF3 and -CO2Me were considered to study the effect on structure, vibrational and electronic properties of tetrathiafulvalene. All the calculations were carried out at density functional theory incorporated with B3LYP exchange functional. The CAM-B3LYP exchange-correlation energy functional was also assessed for the determination of molecular structures. The normal coordinate analysis was performed to compute potential energy distributions of the normal modes which were used for the subsequent normal modes assignment. The temperature dependent Raman spectra have been presented showing the relative reduction in Raman intensity. The ionization of TTF-CN leads a very interesting effect. The IR spectrum of neutral TTF-CN contains a very strong CN stretching band at 2251cm-1 while it is completely diminished in IR spectrum of TTF-CN cation. NBO analyses were also performed to study the electronic structure, second order perturbation and HOMO-LUMO and their energies. Some important thermodynamical parameters have been presented in which entropy calculation reveals below 50% contribution of vibrational motion in all the three molecules.

Measurement of Accurate Interfluorine Distances in Crystalline Organic Solids: A High-Frequency Magic Angle Spinning NMR Approach.

Long-range interatomic distance restraints are critical for the determination of molecular structures by NMR spectroscopy, both in solution and in the solid state. Fluorine is a powerful NMR probe in a wide variety of contexts, owing to its favorable magnetic properties, ease of incorporation into biological molecules, and ubiquitous use in synthetic organic molecules designed for diverse applications. Because of the large gyromagnetic ratio of the 100% naturally abundant 19F isotope, interfluorine distances as long as 20 Å are accessible in magic-angle spinning (MAS) dipolar recoupling experiments. Herein, we present an approach for the determination of accurate interfluorine distances in multispin systems, using the finite pulse radio frequency driven recoupling (fpRFDR) at high MAS frequencies of 40-60 kHz. We use a series of crystalline "molecular ruler" solids, difluorobenzoic acids and 7F-L-tryptophan, for which the intra- and intermolecular interfluorine distances are known. We describe the optimal experimental conditions for accurate distance determinations, including the choice of a phase cycle, the relative advantages of selective inversion one-dimensional versus two-dimensional correlation experiments, and the appropriate numerical simulation protocols. An optimal strategy for the analysis of RFDR exchange curves in organic solids with extended spin interaction networks is presented, which, even in the absence of crystal structures, can be potentially incorporated into NMR structure determination.

Multiply charged energetic metal ion emissions from dinuclear metal complex exposed to intense femtosecond laser fields

Coulomb explosion of nonmetal ions emerged from a variety of molecules has been studied and utilized for the determination of molecular structure and reaction dynamics. In contrast, Coulomb explosion of metal ions, particularly the large Coulombic interactions are expected, has not yet been explored. In this study, the angular distributions of Mnx+ (x = 1–5), Cy+ (y = 1–4), and Oz+ (z = 1–3) emerged from dimanganese decacarbonyl, in which two metal atoms are sandwiched by axial ligands, exposed to intense femtosecond laser fields (1 × 1014–3 × 1015 W cm−2) are investigated. Manganese ions are produced at relatively low laser intensity compared with other transition metal ions with the same charge number but emerged from mononuclear complexes such as metallocenes and metal hexacarbonyls. The kinetic energies of Mn4+ and Mn5+ are described by the simple Coulomb repulsion model of manganese dimer ion. Fairly high kinetic energy of oxygen and carbon ions compared with those emerged from metal hexacarbonyls strongly suggests that atomic ions originating in ligands are repelled by manganese ions at the moment of Coulomb explosion. The use of dinuclear metal complex is advantageous in the production of multiply charged metal ions accompanying high kinetic energy since two manganese ions are in close confinement due to the repulsions with axial ligand (atomic) ions.

Hydrogen-bonded frameworks for molecular structure determination

Single crystal X-ray diffraction is arguably the most definitive method for molecular structure determination, but the inability to grow suitable single crystals can frustrate conventional X-ray diffraction analysis. We report herein an approach to molecular structure determination that relies on a versatile toolkit of guanidinium organosulfonate hydrogen-bonded host frameworks that form crystalline inclusion compounds with target molecules in a single-step crystallization, complementing the crystalline sponge method that relies on diffusion of the target into the cages of a metal-organic framework. The peculiar properties of the host frameworks enable rapid stoichiometric inclusion of a wide range of target molecules with full occupancy, typically without disorder and accompanying solvent, affording well-refined structures. Moreover, anomalous scattering by the framework sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. An ever-expanding library of organosulfonates provides a toolkit of frameworks for capturing specific target molecules for their structure determination.

Crystal structure and Hirshfeld surface analysis of N-(2-(N-methylsulfamoyl)phenyl)formamide: Degradation product of 2-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide

The hydrolysis of 2-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide (2) during crystallization under humidity (85 %) conditions, lead to N-(2-(N-methylsulfamoyl)phenyl)formamide as second step hydrolysis product, identified in the proposed degradation mechanism. Crystal of N-(2-(N-methylsulfamoyl)phenyl)formamide C8H10N2O3S (4), was obtained and characterized. The molecular structure determination was carried out with MoKα X-ray and data measured at 100 K. The compound 4 crystallizes in triclinic P͞1 space group with unit cell parameters a = 4.8465(4) Å, b = 8.1942(9) Å, c = 11.8686(13) Å, α = 77.080(4)°, β = 82.069(4)°, γ = 80.648(4)°, V = 450.76 (8) Å3 and Z = 2. The crystal structure is stabilized by intramolecular N-H···O and intermolecular C-H···O and N-H···O hydrogen bonds that extended as infinite 1D chain along [100]. Stabilization is also ensured by oxygen-π stacking interaction between the aromatic ring and oxygen of the sulfonamide group. The analysis of intermolecular interactions through the mapping of dnorm and shape-index revel that the most significant contributions to the Hirshfeld surface 40.6 and 33.9% are from H···H and O···H contacts, respectively.

Probing gaseous molecular structure by molecular-frame photoelectron angular distributions.

Carbon 1s photoelectron angular distributions of an iodomethane molecule were measured relative to the recoil-frame determined by the momentum correlation between I+ and CH3 + at photoelectron energies of 3, 6.1, and 12 eV. The energy dependent behavior of the recoil-frame photoelectron angular distributions is reproduced reasonably well by the time-dependent density functional theory with B-spline methods. We discuss potential applications of the fully differential photoelectron angular distribution measurements in the molecular frame to three-dimensional molecular structural determinations identifying the directions and lengths of the bonds.

Femtosecond gas-phase mega-electron-volt ultrafast electron diffraction.

The development of ultrafast gas electron diffraction with nonrelativistic electrons has enabled the determination of molecular structures with atomic spatial resolution. It has, however, been challenging to break the picosecond temporal resolution barrier and achieve the goal that has long been envisioned—making space- and-time resolved molecular movies of chemical reaction in the gas-phase. Recently, an ultrafast electron diffraction (UED) apparatus using mega-electron-volt (MeV) electrons was developed at the SLAC National Accelerator Laboratory for imaging ultrafast structural dynamics of molecules in the gas phase. The SLAC gas-phase MeV UED has achieved 65 fs root mean square temporal resolution, 0.63 Å spatial resolution, and 0.22 Å−1 reciprocal-space resolution. Such high spatial-temporal resolution has enabled the capturing of real-time molecular movies of fundamental photochemical mechanisms, such as chemical bond breaking, ring opening, and a nuclear wave packet crossing a conical intersection. In this paper, the design that enables the high spatial-temporal resolution of the SLAC gas phase MeV UED is presented. The compact design of the differential pump section of the SLAC gas phase MeV UED realized five orders-of-magnitude vacuum isolation between the electron source and gas sample chamber. The spatial resolution, temporal resolution, and long-term stability of the apparatus are systematically characterized.

Volumetric Segmentation via Neural Networks Improves Neutron Crystallography Data Analysis.

Crystallography is the powerhouse technique for molecular structure determination, with applications in fields ranging from energy storage to drug design. Accurate structure determination, however, relies partly on determining the precise locations and integrated intensities of Bragg peaks in the resulting data. Here, we describe a method for Bragg peak integration that is accomplished using neural networks. The network is based on a U-Net and identifies peaks in three-dimensional reciprocal space through segmentation, allowing prediction of the full 3D peak shape from noisy data that is commonly difficult to process. The procedure for generating appropriate training sets is detailed. Trained networks achieve Dice coefficients of 0.82 and mean IoUs of 0.69. Carrying out integration over entire datasets, it is demonstrated that integrating neural network-predicted peaks results in improved intensity statistics. Furthermore, using a second dataset, the possibility of transfer learning between datasets is shown. Given the ubiquity and growing complexity of crystallography, we anticipate integration by machine learning to play an increasingly important role across the physical sciences. These early results demonstrate the applicability of deep learning techniques for integrating crystallography data and suggest a possible role in the next generation of crystallography experiments.

Three-Dimensional Nuclear Spin Positioning Using Coherent Radio-Frequency Control

Distance measurements via the dipolar interaction are fundamental to the application of nuclear magnetic resonance (NMR) to molecular structure determination, but they provide information on only the absolute distance r and polar angle θ between spins. In this Letter, we present a protocol to also retrieve the azimuth angle ϕ. Our method relies on measuring the nuclear precession phase after the application of a control pulse with a calibrated external radio-frequency coil. We experimentally demonstrate three-dimensional positioning of individual ^{13}C nuclear spins in a diamond host crystal relative to the central electronic spin of a single nitrogen-vacancy center. The ability to pinpoint three-dimensional nuclear locations is central for realizing a nanoscale NMR technique that can image the structure of single molecules with atomic resolution.

Synthesis, spectroscopy, electrochemistry, and molecular structure of tetrakis{(E)-2-((pyridin-2-ylimino)methyl)phenolato}(hydroxido)0.5(nitrato)1.5-tetracopper(II) nitrate hydroxide

Reaction between (E)-2-((pyridin-2-ylimino)methyl)phenol (HL) and copper(II) nitrate provides tetrakis{(E)-2-((pyridin-2-ylimino)methyl)phenolato}(hydroxido)0.5(nitrato)1.5-tetracopper(II) nitrate hydroxide, [(CuL)4(NO3)1.5(OH)0.5](NO3)(OH) (1). ESI-mass spectra show the ion peaks for the dinuclear species at m/z 565 for [(CuL)2(HCO2)]+ and 521 for [(CuL)2+H]+ and the mononuclear species at m/z 260 for [(CuL)]+. Vibrational spectra show very strong bands at 1604/1546 cm−1 for ν(C = N/C = C) and at 1384, 1351 cm−1 for ν(NO3–). Cyclic voltammograms demonstrate an irreversible redox processes for the Cu(II)/Cu(I) and Cu(I)/Cu(0) couples in acetonitrile. X-ray molecular structure determination explores the formation of a cationic tetranuclear copper(II)-complex, in which a deprotonated ligand molecule chelates to one copper ion with the phenolate-O and imino-N atoms. In addition, a phenolate-O atom bridges between two neighboring copper ions and a pyridine-N atom coordinates to a third copper ion, so that each ligand bridges among three copper ions in a κ2N,O:κO:κN' coordination sphere. Thus, the four copper ions and four chelating-bridging ligands assemble primarily into a cationic [(CuL)4]4+ complex. The two copper ions are further coordinated by either a nitrate anion (75% occupancy) or a hydroxide anion (25% occupancy) and form the core of a tetranuclear [(CuL)4(NO3)1.5(OH)0.5]2+ cation.

π–π interaction leading to an inversion-symmetric complex pair of Λ- and Δ-bis[N-2-(R-pyridyl)-2-oxo-1-naphthaldiminato-κ2N,O]zinc(II)

The Schiff base ligands N-2-(R-pyridyl)-2-hydroxy-1-naphthaldimine (HL) react with the zinc(II) nitrate or acetate to give the Λ- and Δ-bis[N-2-(R-pyridyl)-2-oxo-1-naphthaldiminato-κ2N,O]zinc(II), [Zn(L)2] {R = H (1), 4/6-CH3 (2/3)}. EI-mass spectra show the molecular ion peaks at 558 (1) and 586 (2 or 3). Molecular structure determination for 2·0.5CH2Cl2 crystal reveals that two molecules of the N^O-chelate ligands form a tetrahedral N2O2-coordination sphere around the zinc atom, in which one of the pyridyl-N atom is located towards the metal atom at a close contact ([Zn1…N2] = 2.674 Å). Packing analysis explores that one of the Zn-chelate ring metallacycles forms a reciprocal and rather strong π–π interaction (Cg⋯g = 3.517 Å) with the pyridyl ring of an adjacent molecule and vice versa, and results in an inversion-symmetric complex pair with opposite Λ- and Δ-configurations at the metal centre. The packing analysis is further supported by quantitative analysis of intermolecular interactions with the Hirshfeld surface. The optimized structure and excitation state properties by DFT/TDDFT support the solid state molecular structure and electronic spectra in solution, respectively.