Spectroscopic detection of DNA quadruplexes by vibrational circular dichroism

The four-stranded G-quadruplex motif is a conformation frequently adopted by guanine-rich nucleic acids that plays an important role in biology, medicine, and nanotechnology. Although vibrational spectroscopy has been widely used to investigate nucleic acid structure, association of particular spectral features with the quadruplex structure has to date been ambiguous. In this work, experimental IR absorption and vibrational circular dichroism (VCD) spectra of the model quadruplex systems d(G)(8) and deoxyguanosine-5'-monophosphate (5'-dGMP) were analyzed using molecular dynamics (MD) and quantum-chemical modeling. The experimental spectra were unambiguously assigned to the quadruplex DNA arrangement, and several IR and VCD bands related to this structural motif were determined. Involvement of MD in the modeling was essential for realistic simulation of the spectra. The VCD signal was found to be more sensitive to dynamical structural variations than the IR signal. The combination of the spectroscopic techniques with multiscale simulations provides extended information about nucleic acid conformations and their dynamics.     

Rotationally resolved magnetic vibrational circular dichroism of the paramagnetic molecule NO

Magnetic vibrational circular dichroism (MVCD) enables the measurement of molecular magnetic moments with modest spectral resolution. Due to its paramagnetism, NO gives a much stronger spectral response, about 3 orders of magnitude more intense, than do typical diamagnetic molecules. The molecule thus provides a convenient test for the experiment and theory of paramagnetic rotors. We have measured and analyzed the MVCD, equivalent to the molecular Zeeman spectra, of NO in co-linear magnetic fields of 0.1, 0.2, 2, 4 and 8 Tesla. Similar MVCD intensities were observed for both the (2)Π(1/2) and (2)Π(3/2) components of NO, particularly for high J values, which demonstrates a considerable deviation from pure Hund's case (a) for NO. The g(J)-values for the (2)Π(1/2) components of NO, which can be determined from our experimental spectra by moment analysis, agree well with the predicted values from Radford's theory. For the (2)Π(3/2) components, we tested this theory by simulating the MVCD and absorption spectra, and comparing them with our experimental spectra by use of moment analysis to show that they match well in terms of magnetic properties. While 0.2 T experiments easily develop sufficient MVCD for analysis of NO spectra and these low field intensities have a linear field dependence, spectra in the strong fields accessible in our study showed non-linear response due to onset of saturation effects. We also observed a strong field dependence for the absorption intensities for some (2)Π(3/2) components that was not encompassed in the theoretical model. Finally, a full coupling scheme provided analytical MVCD and absorption intensities that were in good agreement with the experimental values.     

Frenkel‐exciton decomposition analysis of circular dichroism and circularly polarized luminescence for multichromophoric systems

Recently, a method to calculate the absorption and circular dichroism (CD) spectra based on the exciton coupling has been developed. In this work, the method was utilized for the decomposition of the CD and circularly polarized luminescence (CPL) spectra of a multichromophoric system into chromophore contributions for recently developed through‐space conjugated oligomers. The method which has been implemented using rotatory strength in the velocity form and therefore it is gauge‐invariant, enables us to evaluate the contribution from each chromophoric unit and locally excited state to the CD and CPL spectra of the total system. The excitonic calculations suitably reproduce the full calculations of the system, as well as the experimental results. We demonstrate that the interactions between electric transition dipole moments of adjacent chromophoric units are crucial in the CD and CPL spectra of the multichromophoric systems, while the interactions between electric and magnetic transition dipole moments are not negligible. © 2018 Wiley Periodicals, Inc.     

Vibrationally resolved circular dichroism spectra of a molecule with isotopically engendered chirality

We present a theoretical study of vibrationally resolved circular dichroism spectra, both in the adiabatic and non-adiabatic frameworks, with a full account of Franck-Condon and Herzberg-Teller vibrational contributions for the former. Model calculations have been performed on 2(R)-deuteriocyclopentanone, whose chirality is due solely to isotopic substitution. This molecule has two distinct, nearly isoenergetic, half-chair conformations in equilibrium, and its demanding nature in terms of computational accuracy makes it a perfect candidate for performing a detailed comparison between different vibronic models. Comparisons are made with experimental spectra, and we also consider temperature effects. In order to reproduce the experimental spectrum, it is necessary to consider the geometry relaxation occurring during the n→π* transition.     

Complex polarization propagator calculations of magnetic circular dichroism spectra

It is demonstrated that the employment of the nonlinear complex polarization propagator enables the calculation of the complete magnetic circular dichroism spectra of closed-shell molecules, including at the same time both the so-called Faraday A and B terms. In this approach, the differential absorption of right and left circularly polarized light in the presence of a static magnetic field is determined from the real part of the magnetic field-perturbed electric dipole polarizability. The introduction of the finite lifetimes of the electronically excited states into the theory results in response functions that are well behaved in the entire spectral region, i.e., the divergencies that are found in conventional response theory approaches at the transition energies of the system are not present. The applicability of the approach is demonstrated by calculations of the ultraviolet magnetic circular dichroism spectra of para-benzoquinone, tetrachloro-para-benzoquinone, and cyclopropane. The present results are obtained with the complex polarization propagator approach in conjunction with Kohn-Sham density functional theory and the standard adiabatic density functionals B3LYP, CAM-B3LYP, and BHLYP.     

Study of donepezil binding to serum albumin by capillary electrophoresis and circular dichroism

The interaction between human serum albumin (HSA) and the acetylcholinesterase inhibitor donepezil, has been studied by means of capillary electrophoresis frontal analysis (CE/FA) and circular dichroism. CE/FA enabled rapid and direct estimation of the quantity of free donepezil present at equilibrium with a physiological level of serum albumin (600 mol L^–1). Application of Scatchard analysis enabled estimation of the binding parameters of HSA towards donepezil, such as association constant and number of binding sites on one protein molecule. Furthermore, due to enantioseparation ability shown by HSA on donepezil in CE mode, displacement experiments were carried out using ketoprofen and warfarin as coadditives to the HSA based running buffer. The addition of these compounds reduced the enantioresolution of donepezil by HSA only when used at high concentration. These data were confirmed and corroborated by circular dichroism (CD) experiments. Using CD, bilirubin was also applied as a ligand specific to site III of HSA. The observed behaviour suggested that donepezil could be considered a ligand with independent binding to sites I and II; although site III is not the highest affinity site, indirect interaction (i.e. cooperative binding) can be assumed.     

Study of nobiletin binding to bovine serum albumin by capillary electrophoresis–frontal analysis and circular dichroism

A very recent epidemiological study provided strong support for nobiletin (NOB) as a potential candidate chemopreventive agent against cancer. From the pharmacology point of view, drug–protein interactions are determining factors in therapeutic, pharmacodynamic and toxicological drug properties. In this work, for the first time, detection of NOB at near‐physiological conditions was accomplished by means of capillary electrophoresis–frontal analysis (CE‐FA), and then the binding constants of NOB with bovine serum albumin (BSA) at the same conditions were determined. Complexation of NOB–BSA led to a decrease of the height for free NOB with increasing concentration of BSA. These results revealed the presence of a single class of binding site on BSA, and provided the binding constant of 10³/m , showing the strong affinity of NOB for BSA. Furthermore, circular dichroism spectra showed that, when the molar ratio of NOB to BSA was up to 2:1, NOB did not affect the overall protein conformation significantly and the protein thus retained a native‐like structure. These results may provide important information for preclinical studies of nobiletin in pharmaceutical research. Copyright © 2010 John Wiley & Sons, Ltd.     

DNA as helical ruler: exciton-coupled circular dichroism in DNA conjugates

The structure and properties of oligonucleotide conjugates possessing stilbenedicarboxamide chromophores at both ends of a poly(dA):poly(dT) base-pair domain of variable length have been investigated using a combination of spectroscopic and computational methods. These conjugates form capped hairpin structures in which one stilbene serves as a hairpin linker and the other as a hydrophobic end-cap. The capping stilbene stabilizes the hairpin structures by ca. 2 kcal/mol, making possible the formation of a stable folded structure containing a single A:T base pair. Exciton coupling between the stilbene chromophores has little effect on the absorption bands of capped hairpins. However, exciton-coupled circular dichroism (EC-CD) can be observed for capped hairpins possessing as many as 11 base pairs. Both the sign and intensity of the EC-CD spectrum are sensitive to the number of base pairs separating the stilbene chromophores, as a consequence of the distance and angular dependence of exciton coupling. Calculated spectra obtained using a static vector model based on canonical B-DNA are in good agreement with the experimental spectra. Molecular dynamics simulations show that conformational fluctuations of the capped hairpins result in large deviations of the averaged spectra in both the positive and negative directions. These results demonstrate for the first time the ability of B-DNA to serve as a helical ruler for the study of electronic interactions between aligned chromophores. Furthermore, they provide important tests for atomistic theoretical models of DNA.     

Magnetic circular dichroism analysis of crude oil

Optical and magneto-optical properties of solutions of crude oil of different origin (i.e., taken from different fields) are studied in the visible and near-UV region of optical emission. Magnetic circular dichroism (MCD) spectra of oil are obtained in the vicinity of wavelengths of ~410 nm, 533 nm, and 576 nm. It is demonstrated that the intensity of the MCD signal depends on the origin of crude oil, and it is proportional to the oil concentration in the solution. The comparison of the magneto-optical spectroscopy data with the chemical composition of samples allows us to conclude that the observed magneto-optical activity is determined by the presence of VO²⁺ complexes in the oil samples studied. The revealed magneto-optical activity of conventional oil can form a basis of a new method for the analysis of the composition and properties of oil of different origin.     

Reversible plasmonic circular dichroism of Au nanorod and DNA assemblies

Reversible plasmonic circular dichroism (CD) responses are realized for the first time based on temperature-dependent assembly and disassembly of Au nanorod (Au NR) and DNA hybrids. Compared with the conventional UV-vis absorption spectra, the changes in both intensity and line shape of plasmonic CD signals are much more pronounced, leading to a preliminary detection limit of DNA as low as 75 nM. The mechanism and influence factors of reversible plasmonic CD responses are explored.     

Dipeptide structure determination by vibrational circular dichroism combined with quantum chemistry calculations.

The solution structure and the local solvation environments of alanine dipeptide (AD, 1 a) and its isotopomer (AD*, 1 b, 13C on the acetyl end C==O) are studied by using infrared (IR) spectroscopy and vibrational circular dichroism (VCD). From the amide I IR spectra of AD* in various protic solvents, it is found that each of the two carbonyl groups is fully H-bonded to two water molecules. However, the number of alcohol molecules H-bonded to each C==O varies from one to two, and the local solvation environments are asymmetric around the two peptides of AD* in alcohol solutions. The amide I VCD spectra of AD and AD* in D2O are also measured, and a series of density functional theory (DFT, B3LYP/6-311++G**) calculations are performed to obtain the amide I normal-mode rotational strengths of AD and the intrinsic rotational strengths of its two peptide fragments. By combining the VCD-measurement and DFT-calculation results and employing a coupled oscillator theory, we show that the aqueous-solution structure of the dipeptide can be determined. We believe that the present method will be of use in building up a library of dipeptide solution structures in water.     

氨氯地平圆二色谱的理论解析

采用量子化学密度泛函理论(DFT)和含时密度泛函理论(TD-DFT)在B3LYP/6-311++G**水平上对氨氯地平分子的圆二色谱进行理论研究。计算结果表明:振动圆二色谱(VCD)的803、1113、1190、1238、1348、1509、1514、1736、2972、3022和3091 cm-1处存在吸收峰,产生以上吸收峰的振动均涉及到分子手性中心或者所处的基团与分子手性中心形成相关。研究还发现,甲醇溶液使电子圆二色谱(ECD)的吸收峰红移;甲醇溶液中,S-氨氯地平的ECD谱在207、366 nm处存在正性康登效应,223 nm处存在负性康登效应;以上吸收峰均来源于π-π*电子跃迁。这些结论对于深入理解氨氯地平的手征光学性质具有一定的指导意义。     

Determination of binding geometry of DNA-adduct systems through induced circular dichroism

Many molecules (adducts) bound to DNA are postulated to intercalate between successive DNA base pairs. Linear dichroism (LD) has been used to yield information about the angular orientation of the adduct relative to the helix axis, but cannot probe the orientation within the plane perpendicular to this axis. A model is presented in this paper which predicts that the degree of alignment relative to a DNA fixed axis in this plane may be directly probed through the sign of the circular dichroism (CD) induced in an adduct transition of known polarization. Comparison with experimental data suggests that the method can complement LD studies in giving detailed information about the binding geometry.     

Porphyrin protonation studied by magnetic circular dichroism

Magnetic circular dichroism (MCD) spectroscopy provides valuable information about electronic excited states in molecules. The interpretation of spectra is however difficult, often requiring additional theoretical calculations to rationalize the observed signal. Recent developments in time-dependent density functional theory (TDDFT) bring hope that the applicability of MCD spectroscopy for chemical problems may be significantly extended. In this study, two modern analytical TDDFT implementations are compared and used to understand experimental MCD spectra of a model porphyrin system upon protonation. Changes in porphyrin geometry and electronic structure are related to MCD intensities by comparing the spectra of 5,10,15,20-tetraphenyl-21H,23H-porphyrintetrasulfonic acid (TPPS) measured at different pH values with the TDDFT calculations. Although the theoretical results slightly depended on the chosen exchange-correlation functional, the computations provided MCD curves that could well rationalize the experimental data. The protonation of the porphyrin core causes marked changes in the MCD spectrum, whereas the role of the substituents is limited. Also, different conformations of the porphyrin substituents cause relatively minor changes of the MCD pattern, mostly in the Soret region, where the porphine and phenyl electronic transitions start to mix. The solvent environment simulated by the dielectric model caused a shift (~20 nm) of the absorption bands but only minor variations in the absorption and MCD spectral shapes. The study thus demonstrates that the recently available first-principles interpretations of MCD spectra significantly enhance the applicability of the technique for molecular structural studies.     

Rotationally resolved optical rotation and circular dichroism effects for symmetric top molecules induced by a resonant circularly polarized pumping optical field

The rotationally resolved laser-induced optical activity including the laser-induced optical rotation (LIOR) and laser-induced circular dichroism (LICD) effects of an IR probing light pumped by a collinear intense resonant circularly polarized light dependent on the third-order susceptibility due to the pure electric dipole interaction for achiral symmetric top molecules in the gas phase is discussed theoretically. The laser-induced optical activity contains four distinct contributions named A, B, C, and D terms: the B term of the LIOR and LICD arising from the rotational wave function perturbed by the pumping light is deduced using the semiclassical perturbation theory, and the expressions for A, C, and D terms, respectively, due to the ac Stark effect, the Boltzmann statistical redistribution, and the alteration of occupation polability, are obtained from previous results [Zheng, R.-H.; Chen, D.-M.; Wei, W.-M.; He, T.-J.; Liu, F.-C. J. Chem. Phys. 2004, 121, 6835]. The microwave-IR double resonant spectrum is proposed to detect the LIOR and LICD effects. As an example, the LIOR and LICD for the HCF(3) molecules in the conditions of 298.15 K and 0.3 Torr when the IR probing light sweeps over the rotational-vibrational transition of the v(5) and v(1) modes and the right circularly polarized microwave pumping light with the intensity of 1 kW cm(-2) at the resonant frequency 40.84 GHz are calculated on the basis of the B3LYP/6-311++G* computations. The theoretical results indicate that the B term can be of the same order of magnitude as the A and D terms, and the LIOR and LICD can be measurable in comparison to the rotationally resolved MVCD. The laser-induced optical activity may provide useful new information and form a basis for a different kind of optical activity spectroscopy.     

Cobaltocenium acetylsalicylate: synthesis and circular dichroism study of interactions with DNA

Russian Chemical Bulletin - Cobaltocenium acetylsalicylate was synthesized and characterized for the first time. The concentration dependences observed in its interaction with the double helix of...     

3,3-disubstituted piperidin-4-ones. Conformational analysis by NMR and circular dichroism methods

Using¹H and¹³C NMR spectroscopy, we have established the conformational inhomogeneity of chiral 3, 3-disubstituted pipe ridin-4-ones. The conformer with an equatorial methyl group on the C₍₃₎ atom predominates in the conformational equilibrium. For (1S, 3S)-1-(l' phenylethyl)-3-(2-cyanoethyl)- and 1,3-dimethylpiperdin-4-ones, we found¹H NMR spectral parameters which may serve as criteria for conformational homogeneity of piperidin-4-one molecules. The conformational composition of the (3S)-enantiomers of 1,3-dimethyl-3-(2-cyanoethyl)-and 1,3-dimethyl-3-(2-carbomethyl)piperidine-4-ones was also estimated on the basis of theoretical analysis of the circular dichroism spectra in solvents of different polarities.M. V. Lomonosov State UniversityMoscow119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 926–940, July, 1994. Original article submitted June 11, 1994.