Beginners guide to circular dichroism

Rodger, Alison; Marshall, Doug

doi:10.1042/bio_2020_105

Cited by 10 publications

(13 citation statements)

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“…There is strong evidence for the helical arrangements: all CD profiles from the films, including those with different macroscopic orderings (Figure ), share the same bisignate CD profile, with the zero-point aligned with the 324 nm MSC absorption peak. A couplet’s center aligned with the absorbance peak strongly suggests an exciton-coupled or coupled-oscillator system. , Additionally, in an exciton coupled system, the increased chiroptic signal can be directly attributed to enhanced coupling from a change to the cluster-to-cluster distance or to the dihedral angle between electronic transition dipoles, ,, as nicely shown in recent reviews. ,, These changes would be brought about by the different evaporative processing conditions. As for the core, the results of this work do not confirm or refute the chirality of the core.…”

Section: Resultsmentioning

confidence: 62%

“…A couplet's center aligned with the absorbance peak strongly suggests an exciton-coupled or coupled-oscillator system. 47,48 Additionally, in an exciton coupled system, the increased chiroptic signal can be directly attributed to enhanced coupling from a change to the clusterto-cluster distance or to the dihedral angle between electronic transition dipoles, 17,24,49 as nicely shown in recent reviews. 2,47,48 These changes would be brought about by the different evaporative processing conditions.…”

Section: Resultsmentioning

confidence: 73%

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Extracting Pure Circular Dichroism from Hierarchically Structured CdS Magic Cluster Films

et al. 2022

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Chiroptically active, hierarchically structured materials are difficult to accurately characterize due to linear anisotropic contributions (i.e., linear dichroism (LD) and linear birefringence (LB)) and parasitic ellipticities that produce artifactual circular dichroism (CD) signals, in addition to chiral analyte contributions ranging from molecular-scale clusters to micron-sized assemblies. Recently, we have shown that CdS magic-sized clusters (MSC) can self-assemble into ordered films that have a hierarchical structure spanning seven orders of length-scale. These films have a strong CD response, but the chiral origins are obfuscated by the hierarchical architecture and LDLB contributions. Here, we derive and demonstrate a method for extracting the “pure” CD signal (CD generated by structural dissymmetry) from hierarchical MSC films and identified the chiral origin. The theory behind the method is derived using Mueller matrix and Stokes vector conventions and verified experimentally before being applied to hierarchical MSC and nanoparticle films with varying macroscopic orderings. Each film’s extracted “true CD” shares a bisignate profile aligned with the exciton peak, indicating the assemblies adopt a chiral arrangement and form an exciton coupled system. Interestingly, the linearly aligned MSC film possesses one of the highest g-factors (0.05) among semiconducting nanostructures reported. Additionally, we find that films with similar electronic transition dipole alignment can possess greatly different g-factors, indicating chirality change rather than anisotropy is the cause of the difference in the CD signal. The difference in g-factor is controllable via film evaporation geometry. This study provides a simple means to measure “true” CD and presents an example of experimentally understanding chiroptic interactions in hierarchical nanostructures.

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Section: Resultsmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 73%

Extracting Pure Circular Dichroism from Hierarchically Structured CdS Magic Cluster Films

et al. 2022

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“…A similar change in the sign of the circular dichroism signal was observed for chiral CDs synthesized from l - or d -glutathione in aqueous alkali with increasing electrolysis time 58 . Since circular dichroism can provide evidence of conformational changes in chiral chromophores, including self-assembly of superstructures 51 , 59 , we speculate that the sign change observed here may have originated from displacement of chromophoric groups related to n–π* optical transitions. A detailed study of this effect will be a subject of forthcoming work.…”

Section: Resultsmentioning

confidence: 79%

Revealing the nature of optical activity in carbon dots produced from different chiral precursor molecules

et al. 2022

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Carbon dots (CDs) are light-emitting nanoparticles that show great promise for applications in biology and medicine due to the ease of fabrication, biocompatibility, and attractive optical properties. Optical chirality, on the other hand, is an intrinsic feature inherent in many objects in nature, and it can play an important role in the formation of artificial complexes based on CDs that are implemented for enantiomer recognition, site-specific bonding, etc. We employed a one-step hydrothermal synthesis to produce chiral CDs from the commonly used precursors citric acid and ethylenediamine together with a set of different chiral precursors, namely, L-isomers of cysteine, glutathione, phenylglycine, and tryptophan. The resulting CDs consisted of O,N-doped (and also S-doped, in some cases) carbonized cores with surfaces rich in amide and hydroxyl groups; they exhibited high photoluminescence quantum yields reaching 57%, chiral optical signals in the UV and visible spectral regions, and two-photon absorption. Chiral signals of CDs were rather complex and originated from a combination of the chiral precursors attached to the CD surface, hybridization of lower-energy levels of chiral chromophores formed within CDs, and intrinsic chirality of the CD cores. Using DFT analysis, we showed how incorporation of the chiral precursors at the optical centers induced a strong response in their circular dichroism spectra. The optical characteristics of these CDs, which can easily be dispersed in solvents of different polarities, remained stable during pH changes in the environment and after UV exposure for more than 400 min, which opens a wide range of bio-applications.

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“…For atropisomers with the atropisomeric axis being the only chiral center, spectroscopic techniques such as NMR in the presence of a suitable chiral shift reagent can also be used . Another technique is circular dichroism (CD) which relies on the ability of individual enantiomers, such as atropisomers, to rotate plane polarized light …”

Section: Early Development Of Route To Pure Atropisomer Drug Candidatementioning

confidence: 99%

“…24 Another technique is circular dichroism (CD) which relies on the ability of individual enantiomers, such as atropisomers, to rotate plane polarized light. 25 For batch release, analytical methods capable of separating all potential stereoisomers are preferred for reliably determining the stereoisomeric purity of the drug candidate. When releasing 1 and 2 for the preclinical studies, we choose to use chiral SFC as the analytical method.…”

Section: Analytical Challenges For Batch Releasementioning

confidence: 99%

Approaches to Synthesis and Isolation of Enantiomerically Pure Biologically Active Atropisomers

et al. 2022

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Metrics & MoreArticle Recommendations CONSPECTUS: Atropisomerism is a stereochemical phenomenon exhibited by molecules containing a rotationally restricted σ bond. Contrary to classical point chirality, the two atropisomeric stereoisomers exist as a dynamic mixture and can be interconverted without the requirement of breaking and reforming a bond. Although this feature increases structural complexity, atropisomers have become frequent targets in medicinal chemistry projects. Their axial chirality, e.g., from axially chiral biaryl motifs, gives access to unique 3D structures. It is often desirable to have access to both enantiomers of the atropisomers via a nonselective reaction during the early discovery phase as it allows the medicinal chemistry team to probe the structure activity relationship in both directions. However, once a single atropisomer is selected, it presents several problems. First, the pure single atropisomer may interconvert to the undesired stereoisomer under certain conditions. Second, separation of atropisomers is nontrivial and often requires expensive chiral stationary phases using chromatography or additives if a salt resolution approach is chosen. Other options can be kinetic resolution using enzymes or chiral catalysts. However, apart from the high cost often associated with the two latter methods, a maximum yield of only 50% of the desired atropisomer can be obtained. The ideal approach is to install the chiral atropisomeric axis enantioselectively or employing a dynamic kinetic resolution approach. In theory, both approaches have the potential to provide a single atropisomer in quantitative yield. This Account will discuss the successes/failures and challenges we have experienced in developing methods for resolution/separation and asymmetric synthesis of atropisomeric drug candidates in one of our early phase drug development projects. Suitability for the different methods at various stages of the drug development phase is discussed. Depending on the scale and time available, a separation of a mixture of atropisomers by chromatography was sometimes preferred, whereas asymmetric-or resolution approaches were desired for long-term supply. With the use of chromatography, the impact on separation efficiency and solvent consumption, depending on the nature of the substrate, is discussed. We hope that with this Account the readers will get a better view on the challenges medicinal and process chemists meet when designing new atropisomeric drug candidates and developing processes for manufacture of a single atropisomer.

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Beginners guide to circular dichroism

Abstract: Circular dichroism (CD) is used to give information about the chirality or handedness of molecular systems. It is particularly widely applied to determine the secondary structure of proteins such as biopharmaceutical products.

Cited by 10 publications

References 0 publications

Extracting Pure Circular Dichroism from Hierarchically Structured CdS Magic Cluster Films

Extracting Pure Circular Dichroism from Hierarchically Structured CdS Magic Cluster Films

Revealing the nature of optical activity in carbon dots produced from different chiral precursor molecules

Approaches to Synthesis and Isolation of Enantiomerically Pure Biologically Active Atropisomers

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