Stereochemistry, the precise 3D arrangement of atoms in a molecule, is a fundamental determinant of a drug candidate's pharmacological activity, metabolic stability, and toxicity profile. In early drug discovery and development, confirming the absolute configuration and enantiomeric purity is non-negotiable for establishing accurate Structure-Activity Relationships (SAR). BOC Sciences offers expert Stereochemistry Confirmation services, utilizing an orthogonal approach that combines X-ray Crystallography (SC-XRD), Advanced NMR techniques, and Chiroptical spectroscopy (ECD/VCD). We assist medicinal chemists and structural biologists in unambiguously assigning stereocenters, resolving racemic mixtures, and verifying spatial structures, ensuring that your R&D decisions are based on the correct molecular geometry.
BOC Sciences delivers definitive stereochemical assignments to validate your chemical synthesis and support accurate biological evaluation.
The unambiguous "gold standard" for stereochemistry. We offer crystal growth screening and diffraction analysis to directly visualize the 3D structure and assign absolute configuration using anomalous dispersion (Flack parameter).
We utilize 1D and 2D NMR techniques (NOESY/ROESY) to determine relative stereochemistry. For absolute configuration, we employ chiral derivatizing agents (e.g., Mosher's acid analysis) to deduce configuration based on chemical shift anisotropy.
For non-crystalline samples, we compare experimental ECD spectra with time-dependent DFT (TD-DFT) calculated spectra. This powerful method assigns absolute configuration by matching the Cotton effects of chromophores.
VCD extends chiroptical analysis to the infrared region, providing stereochemical data rich in conformational information. It is particularly useful for molecules lacking strong UV chromophores or those that are difficult to crystallize.
We utilize a vast library of chiral stationary phases (CSPs) and supercritical fluid chromatography (SFC) to separate enantiomers. This not only determines purity but also allows for the isolation of pure isomers for individual biological testing.
A fundamental characterization technique. We provide precise measurement of specific rotation [α] values at various wavelengths and temperatures to benchmark the optical activity of your synthesized compounds against literature or theoretical values.
BOC Sciences supports the structural confirmation of diverse chemical entities, ensuring the integrity of your discovery pipeline from hit generation to lead optimization.
Submit your molecular structure or chemical data, and BOC Sciences will design the optimal strategy to confirm its configuration and purity.
We evaluate the molecule's properties (solubility, chromophores, crystallinity) to select the most definitive method (XRD, NMR, or ECD/VCD) for assignment.
Samples are purified or derivatized if necessary. For XRD, we perform high-throughput screening to grow diffraction-quality single crystals.
High-resolution spectra or diffraction data are collected. Parallel DFT calculations are run to simulate theoretical spectra for comparison with experimental results.
We analyze the convergence of data to assign absolute configuration. A detailed report containing ORTEP diagrams, spectra, and assignment justification is delivered.
In the Hit-to-Lead phase, knowing the active enantiomer is critical. Our rapid stereochemical confirmation helps medicinal chemists refine SAR models by ensuring biological data is correlated with the correct 3D isomer, preventing pursuit of "eutomers" based on incorrect structural assumptions.
When developing enantioselective synthetic routes, we provide quick feedback on the stereochemical outcome of key reaction steps. This allows synthetic chemists to adjust catalysts and conditions rapidly to maximize enantiomeric excess (ee).
For projects relying on chiral resolution, we determine the efficiency of separation processes. We analyze fractions to confirm optical purity and assign the configuration of separated isomers, facilitating the selection of candidates for downstream assays.
Stereoisomeric impurities can have vastly different biological effects. We assist in identifying and characterizing stereoisomeric impurities in research batches, ensuring that observed toxicities or potencies are not misattributed to the wrong molecular species.
Partner with BOC Sciences to confidently assign absolute configuration and assess chiral purity. Our integrated platform of XRD, NMR, and Chiroptical methods provides the structural certainty required to advance your drug discovery programs.
We don't rely on a single method. By cross-validating results using XRD, NMR, and ECD, we provide high-confidence assignments even for difficult-to-crystallize oils or molecules with flexible conformations.
Our in-house computational team performs advanced DFT and TD-DFT calculations to support spectroscopic data, enabling ab initio assignment of absolute configuration without the need for reference standards.
Understanding that speed is critical in discovery, we offer streamlined workflows for chiral screening and structural confirmation, delivering data quickly to keep your synthesis and biology teams moving forward.
From macrocycles to PROTACs and natural products, our team has extensive experience handling structurally complex molecules that pose challenges for standard analytical techniques.
Client Needs: A medicinal chemistry team synthesized a novel lead compound with two chiral centers but was unsure of the relative and absolute configuration, which was critical for patent protection and SAR analysis.
Challenges: The compound failed to crystallize despite extensive screening, ruling out X-ray diffraction. Standard NMR NOE studies were ambiguous due to signal overlap, leaving the team unable to confirm which diastereomer was the active agent.
Solution: BOC Sciences implemented a rigorous orthogonal verification strategy combining NMR chemical shift anisotropy (Mosher's method) with VCD. We performed precise chiral derivatization to deduce configuration locally, while simultaneously running advanced DFT computational modeling to predict VCD spectra for all isomers. This dual-platform approach cross-validated the results, eliminating ambiguity where single methods failed.
Outcome: We successfully assigned the absolute configuration as (S,S). This allowed the client to focus their synthesis efforts on the correct isomer, significantly saving resources in the scale-up phase.
Client Needs: A biotech client identified a "hit" from a library screening that was a racemic mixture. They needed to separate the enantiomers and identify which one possessed the desired biological activity.
Challenges: The separation was difficult due to the molecule's polarity. Furthermore, the client needed sufficient quantities of both enantiomers rapidly to proceed with in vitro assays, but had no established chiral method.
Solution: Leveraging our extensive library of chiral stationary phases, we utilized Supercritical Fluid Chromatography (SFC) for high-throughput method screening. We successfully developed a robust separation protocol within 48 hours that resolved the polar enantiomers and seamlessly transitioned to preparative-scale isolation. This ensured high recovery rates while maintaining strict enantiomeric purity (>99% ee) for biological testing.
Outcome: The client received pure enantiomers within two weeks. Subsequent testing revealed that the (R)-enantiomer was 100-fold more potent, enabling a precise focus for the next round of lead optimization.
Client Needs: A researcher working on natural product total synthesis needed to verify that their synthetic intermediate matched the natural product's stereochemistry.
Challenges: The intermediate was an oily substance available in only milligram quantities. Traditional crystallization was impossible, and the specific optical rotation value was too low to be reliable for assignment.
Solution: To overcome the lack of crystallinity, we applied advanced ECD coupled with TD-DFT calculations. Our experts performed comprehensive conformational searches and Boltzmann-weighted spectral averaging. By achieving a precise match between the experimental Cotton effects and the theoretical model, we provided definitive structural proof without the need for crystals.
Outcome: The high correlation between experimental and calculated spectra confirmed the synthetic intermediate had the inverted configuration compared to the target. This critical insight saved the client from proceeding with a flawed synthesis route.
Confirmation of chiral centers typically relies on high-resolution NMR, chiral chromatography, and optical activity measurements. BOC Sciences integrates multiple analytical techniques, comparing experimental data with theoretical models to precisely identify the absolute configuration of each chiral center, providing reliable stereochemical information for complex molecules.
Stereoisomers have subtle differences, making single analytical methods insufficient. BOC Sciences combines NMR, CD spectroscopy, and chiral separation techniques to accurately differentiate stereoisomers, ensuring clients obtain precise stereochemical information to support molecular design and subsequent research.
Method selection depends on molecular complexity, number of chiral centers, and information requirements. BOC Sciences develops customized strategies based on project characteristics, integrating spectroscopy, chiral chromatography, and computational modeling to achieve efficient and accurate stereochemical confirmation while minimizing analysis risks and enhancing result reliability.
Multi-chiral molecules present conformational flexibility and interdependent chiral centers. BOC Sciences uses multi-technique integration, including NMR, chiral chromatography, and computational modeling, to systematically analyze each chiral center, ensuring accurate resolution and reliable validation of the overall stereochemical information in complex molecules.
The reliability of stereochemical confirmation depends on data integrity and analytical expertise. BOC Sciences applies multi-angle cross-validation and expert interpretation, combining experimental and theoretical data in a closed-loop workflow, providing clients with reproducible, trustworthy stereochemical confirmation results and supporting informed R&D decisions.
We were stuck on the stereochemistry of our lead series for weeks. BOC Sciences' team used their ECD and computational expertise to provide a definitive answer. Their report was detailed and scientifically rigorous, giving us the confidence to proceed.
— Dr. Adams, Principal Scientist, Drug Discovery Biotech
The speed at which BOC Sciences developed a method and separated our racemic mixture was impressive. We received high-purity isomers faster than expected, which accelerated our biological screening significantly.
— Dr. Lee, Chemistry Team Leader, Pharma R&D
We sent a challenging sample for X-ray analysis that other labs failed to crystallize. BOC Sciences succeeded in growing diffraction-quality crystals and provided the absolute configuration we desperately needed.
— Dr. Jones, Senior Researcher, Synthetic Chemistry
Accurate stereochemical assignment is crucial for our modeling. BOC Sciences acts as a reliable partner, ensuring our structural data is correct so our computational models predict binding affinity accurately.
— Dr. Taylor, Head of Computational Chemistry, Research Institute
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