Elucidate Unknown Structures | What's New in ACD/Structure Elucidator Suite

Version 2021

Version 2021 of Structure Elucidator Suite adds new features, including determination of molecular configuration using residual dipolar couplings and new parameters to help with structure verification. It also improves existing functions. Read below for details, and contact us for help upgrading your software.

New Features

Use Residual Dipolar Couplings (RDCs) for Determination of Molecular Configuration

You can now measure RDCs from 2D spectra. You can fit these couplings to the 3D structures of conformers to help with determination of molecular configuration.

The fit of the RDC to a given conformer is quantified by the Cornilescu Quality Factor (Q). A lower Q indicates a better fit.

Pick peaks and measure RDCs from 2D spectra recorded in isotropic and anisotropic media

Table of Spectral Data displaying the isotropic and anisotropic coupling constants and the residual dipolar couplings

After RDCs are measured, the Table of Spectral Data gains 3 new columns (J, T, and D) containing the isotropic and anisotropic coupling constants and the residual dipolar couplings

The software fits the RDCs to all generated or imported conformers' structures, and calculates the Q value. A Q below 0.1 indicates that a conformer structure has a high probability of being the correct one.

Identify the Best Structure During Structure Verification with New Metrics and Parameters

You can now use the NMR Purity parameter to evaluate structural candidates with similar match factors (MFs)

NMR Purity is defined as the ratio between the summed integrals of the assigned protons and the summed integrals of the entire spectrum

Catechin is likely the correct structure since it has a much higher calculated NMR Purity

Peaks corresponding to both Catechin and one of its subfragments can be found in an experimental spectrum. Since MF only looks for peaks in the spectrum appropriate for each structure and ignores extraneous peaks, both structures have high MFs. However, catechin has a much higher calculated NMR Purity, indicating that it is more likely the correct structure.

You can now use DP4 metrics in CCV and UBV to better rank generated candidates with similar MFs

This parameter is calculated using the predicted chemical shifts and their corresponding error distribution. It is a multiplicatively calculated statistical value and gives the probability that a structure from a set is the correct one.

DP4 metrics help you distinguish between two or more fully assigned candidate structures with similarly high MFs.

When two or more fully assigned candidate structures have similarly high MFs, DP4 metrics help you distinguish between them. A DP4 value closer to 100 indicates a higher probability of that structure being correct.

Define Co-existing Rotamers in NMR Spectra

You can now define and report co-existing rotamers. Select the rotamer peaks in your spectrum and identify them as rotamers. You can then adjust the proton ratios with 0.1H accuracy.

By defining H3a protons as doublets, you can adjust their proton ratios to sum to 1

In the above structure, rotation around the amide bond is restricted, leading to 2 rotamers being formed. By defining H3a protons as doublets, you can adjust their proton ratios to sum to 1. This functionality is found in the Multiplet Analysis dialog box.

1H NMR (DMSO-d₆) δ: 8.47 (d, J=7.0 Hz, 0.4H rotamer), 8.18 (d, J=7.0 Hz, 0.6H rotamer)

Report multiplet results for samples containing rotamers in US patent format, or create customized reports in most other formats

Unfold Folded 2D Spectra to Get the True Position of Peaks

You can now unfold folded 2D spectra along the F1 axis to reveal the correct positions of peaks

Apply process-correct aliased frequencies to adjust the spectrum along F1 range. After unfolding, the signals appear at their correct position around 220ppm (right)

Left: overlaid HMBC (red) and HSQC (green) spectra of azithromycin. The signals from HMBC appearing at ~0 ppm in ¹³C belong to folded peaks. Their true position is greater than the HMBC upper F1 range. Apply process-correct aliased frequencies to adjust the spectrum along F1 range. After unfolding, the signals appear at their correct position around 220ppm (right).

Improved Features

Automated Evaluation of Singly Charged Nitrogen Salts

On structures with multiple nonequivalent nitrogen atoms, you can automatically explore the possibilities of a positive charge on each nitrogen.

Previously, the software automatically detected the possibility of a positively charged nitrogen. But if there were several nonequivalent nitrogens, you had to consider all possibilities manually. Now, the software creates several MCDs by placing the charge on each nitrogen, and runs them in parallel to get the correct structure.
Enable this feature by selecting Enumerate Possible Charge of N Atoms in the Generator Options section of the Check MCDs Options dialog box

Enable the automated consideration of singly charged nitrogen salts by selecting the Enumerate Possible Charge of N atoms checkbox — Enable the automated consideration of singly charged nitrogen salts by selecting the **Enumerate Possible Charge of N atoms** checkbox

AutoMCDs Include 2-Bond C-F Connections

The software can now create C-F connections in the autoMCD based on ¹³C-¹⁹F ²J values taken from ¹³C spectra

Structure Aware Analysis in 2D Spectra of P- and F-Containing Compounds

You can now use the structure aware analysis algorithm to automatically recognize ¹⁹F-¹H and ¹⁹F-¹³C multiplets in HMBC or HSQC spectra without a 1D ¹³C NMR spectrum

Control of Alignment Options of Spectra in Batch ASV

You now have control of alignment options of 2D spectra and corresponding 1D curves in Batch ASV

Integrate All Peaks in Series of NMR Data

In Group mode, view peak integral values for all spectra in a series

Display and selectively position the integral values for all peaks in a 1D 1H NMR series in group mode.

A series of 1D ¹H NMR spectra for ethylindanone. In group mode, you can display and selectively position the integral values for all peaks in the series.

Refinements in Database Search Capabilities

More Data Types Can Be Included in Database Records

You can now represent large/complex molecules using graphical objects with defined formulas and modify them by attaching traditional chemical structures. The entire structure may be used in calculations and searches.

Represent complex molecules with graphical objects, e.g., proteins, antibody-drug conjugates, nanoparticles on surfaces, etc.

Include multiple plots and charts to visualize datasets in records

Include multiple plots and charts to visualize datasets in records

Improved Search for Data Range Values and Molecules with Chiral Centers

Improved definition of ranged values. Search results of ranged values are more reproducible (e.g., when searching for compounds with a melting point of 65°C, record sets with the following in the melting point field will now be returned: 50-100°C, <100°C, >50°C)
Improved search for structures that contain chiral atoms with "&" and "or" enhanced stereo labels (where "&" denotes a racemic center and "or" denotes relative configuration). Previously the labels provided incomplete/incorrect search results. [+]

Server Side Improvements

We added new capabilities to mirrored databases:

Read/write access
Ability to select records for mirroring

Improved logging of transactions to the database, e.g., view all successful and failed user logins
You can provide administrative privileges (to create, edit, and/or delete record sets) to LDAP users or groups

Improved Data Import

We improved data import from:

Shimadzu LabSolutions CDS—you can now import data via the Connect to External Application dialog box or the ACD/Labs/Shimadzu LabSolutions CDS Add-on
Agilent OpenLab CDS—you can now select a whole folder or several files to import at once, via the Connect to External Application dialog box or the Add-on
Thermo Chromeleon—you can now import LC/MS data, via the Connect to External Application dialog box or the Add-on

Features for Other Techniques

You can process data from other analytical techniques in Structure Elucidator Suite. We've improved features for these techniques as well:

Analysis of MS & Chrom Data with Structure Elucidator Suite
Display Fragment Structures as Peak Annotations
- You can now annotate peaks with their associated fragment structures. This works with fragment structures assigned manually or via Auto Assignment.
Record and Automate Frequent Actions
- Record automatic and manual processing actions for LC/UV/MS data in the Recording Log. Stop and start recording by clicking Recording in the toolbar or by using the Recording Log dialog box.
- Automate actions by generating a script from actions saved in the Recording Log
Access More Features by Converting Flat Chromatograms into Hyphenated Data
- Turn flat (single-channel) chromatograms into hyphenated data to access Projects and the Table of Components. Now single-channel and multi-dimensional datasets will have a consistent look.
Get Better Results from Automatic Processing with IntelliXtract 2.0 and IXCR 2.0
- You can now set an Abundance Threshold for components to be identified via spectral search
- Auto Interpret Component Spectrum now gives more accurate adduct labels. We added checks for adduct pairs like [M+NH3+H]+. We also improved annotation of multiply charged ions and multimers.
- You can now see the retention time difference (tR Difference) between experimental and reference chromatograms in the Table of Components
- We made spectral search faster
Improve Processing with More Tools and Options
- You can now match peaks between chromatograms in an LC/MS series. Both manual and automatic matching are available. Previously, peak matching was only available between datasets opened in separate windows (not in series mode).
- Subtract one DAD (diode array detector, LC/UV) dataset from another, e.g., you can correct a sample chromatogram and spectrum by blank subtraction
- We improved the peak detection algorithm, and added the Baseline Liftoff and Baseline Touchdown options, so you can refine the integration by moving the start and end points of the peak
- Generate formulae for multiple m/z values within a mass spectrum, while setting individual parameters for each mass range
- You can now annotate spectra with fragment losses (e.g., loss of HCl)
Filter MS Searches by Polarity
- When searching databases by spectra, the search now returns only reference spectra with the same polarity as the query

Previous Software Versions

Version 2020
Data Analysis
- Save time with real-time generation and ranking of structures during elucidation and identify the best structure at any time, even before the generation process is complete
- More efficiently determine the best structure using DP4 metrics. This approach calculates the Match Factor based on the normalized multiplication of probabilities of each assigned atom (¹³C or ¹H). This enables much better structural candidates' discrimination compared to averaged-based approaches.
- Conformer optimization and analysis using NOESY/ROESY spectra
- Swap assignments of diastereotopic CH₂ groups in 3D conformers to potentially obtain better fit for inter-proton distances
- Perform Unbiased Verification (UBV) without full carbon assignment—partial structure assignment (25% assignment of carbons) is sufficient
- Several enhancements and performance improvements in Mixture Analysis workflow as follows:
- Improved Match Factor calculation for nitrogen containing compounds
- "TMS aware" analysis— only the smallest peak closest to 0 ppm is automatically identified as TMS if the proposed structure contains a Si-CH₃ group
- Improved peak picking of small signals in overlapped regions of 2D spectra for more accurate data analysis
- Correctly identify NOESY peaks corresponding to negative NOE
Ease of Use
- Visualize peak assignments on the spectra of matched fragments/structures
- Choose to display the distance error between observed and best fit distance values over NOE arrows for convenient data analysis
- Automatic adjustment of nitrogen valence based on the manually defined charge
- Delete 2D annotations and dark regions directly in the spectrum with a single click
- Higher integral maximum (>32,000) to accommodate the larger dynamic range in modern high field NMR instruments
- Flag critical correlations on the structure and related peak(s) for quick review
Mark and view the critical correlations on the structure and related peak(s).

Improvements in Prediction Capabilities
- Predict spectra of whole polymers—both the end groups and the main chain
- Predict APT and DEPT ¹³C spectra directly in the prediction interface (initial prediction of ¹³C NMR not necessary)
Reporting
- Added option to include chemical shifts for ¹⁹F, ³¹P, and other X nuclei in reports
Databasing

Database Client
- Attach files to lines in tables (Word, PDF, Excel, JPEG, etc.)
- Connect record sets by User Data to display linked meta data
- Consistency in the handling of "dates"—computer default date setting may be enforced; user may select the date format of imported fields
SpectrusDB Server
- PostgreSQL database server 12.2 included in installation package
- Improved performance for remote databases through mirroring of record sets between two Spectrus DB Enterprise servers (read only)
- Manage Database groups and Users when LDAP or Custom Authentication is active
- Update of audit trail upon change of record ownership
Technique-Specific Features

Structure Elucidator Suite contains spectral processing capabilities for a variety of other analytical techniques.
- Processing and Analysis of LC/MS Data with Structure Elucidator
  Data Import
  - A new "Connect To" plug-in allows data import from Agilent™ OpenLab™
  - Data import from Waters™ MassLynx™ version 4.2
  - Upgraded data import from Thermo Scientific™ Xcalibur™
  - Import additional information from Shimadzu® LabSolutions™ including component spectra, information about components and peaks, XIC curves, and peaks detected in SIM and MRM traces
  Data Analysis
  
  IXCR (Structure ID by Database Search)
  - Conveniently match components identified by database search to the reference database and record of the candidate structure
  - Search databases with MS2 spectra that do not contain a parent m/z ion (e.g., spectra acquired with Data Independent Acquisition)
  - Easily compare the retention time of a component to that of its candidate structure and view the retention time difference in the Table of Components
  Quantitation
  - Quantitatively analyze chromatographic data
  A calibration curve is automatically generated from chromatograms of calibration standards.
  
  Peak Integration
  - Choose how to calculate XIC area %—either by using a single ion (Single mode) or by summing together all fragment, adduct, and component ions (Summed mode)
  Retention Time
  - Calculate relative retention time for GC-FID data
  - Import retention time from *.SDF files into the Table of Components
  Manage Data from Multiple Instruments
  
  Keep track of settings for each instrument by setting up instrument profiles
  - Make profiles for single chromatogram data using the new Chrom Profile Manager—set and save chromatogram parameters for each profile
  - New features for LC/UV/MS profiles
  Data Display
  - Easily see which scans are averaged to produce a component mass spectrum
  - View InChI and SMILES structural descriptors in the Table of Components
  - Customize the number of decimal places displayed for assigned and XIC m/z values in the LC/UV/MS legend
  - Lock x-axis display range for spectra in LC/UV/MS datasets
  Reporting
  - Report LC/MS and LC/UV traces with or without baseline subtraction
  - Toggle on/off the "Ion Mode" label on mass spectra
  - Toggle on/off the labels of MS curves
Version 2019
As of v2019 ACD/Spectrus is compiled in a 64-bit architecture allowing the software to take greater advantage of system resources.

Data Import

We continue to improve and support all major instrument vendor data formats. This version includes enhancements to the following:
- Support for JEOL Delta™ DOSY data
- Improved support for MAGRITEK® data
- Support for Q.OneTec data
- Improved import/export options for JCAMP files
- Full support for 1D NOESY and ROESY datasets and improved import defaults for 2D NOESY and ROESY spectra
- Basic support for NOAH experiments
- Improved support of Shimadzu data
- Read 'Extended Statistics' metadata for Waters™ MassLynx™
- Improved support for processed data from Empower™ (Waters), Chromeleon™ and Atlas™ (Thermo Scientific™) CDSs
- Import processed data from Chromeleon chromatography data systems (CDS) via a new add-on
Data Analysis
- Full support of 1D or 2D NOESY and ROESY spectra for 3D structure elucidation
- Automatically generate stereoisomers from a flat structure and rank them using data from NOESY/ROESY spectra
- New multi-thread processing algorithm provides 1.3-10 times faster structure generation and filtering speed
- Full support for proposed structures containing stereochemistry information
- Automatically distinguish CH₃ from CH groups if edited HSQC or DEPT information is provided
- Unbiased Verification may now be performed using only 1D ¹H, HMBC, and HSQC spectra (1D ¹³C spectrum is no longer required)
- Easily identify possible erroneous data using the diagnostic orange colored cells in the Table of Spectral Data
- Improved options for automatic alignment of ¹⁵N spectra
- Automatic alignment can now be performed using 1D NOESY or 1D ROESY
- Improved support for synchronization of APT and HSQC spectra
- Streamline the analysis of mixtures by applying Targeted Profiling to 1D spectra of samples with known composition and variable concentrations of components
- Structure Aware Analysis now supports automatic peak picking in ¹³C spectra of compounds containing ³¹P, as well as ¹⁹F atoms
- Easily import and use corresponding *.spectrus files as 1D projections for your 2D spectra
- Display a larger dynamic range to accommodate newer instruments
- 'Known Structures Search' results from PubChem databases now display IUPAC names
- Achieve faster, more accurate predictions with the improved Neural Network algorithm
- Access an extended Predictors training database
Databasing
- Improved default options for updating the ¹⁵N prediction databases
Reporting
- Improved structure display for mixture components
- Expended options for reporting peak assignments
Ease of Use
- 'Proposed Structure' has been replaced by 'Proposed Molecule' for better consistency across the product portfolio
- Improved performance of the interface when re-opening projects
- Ability to display all the assignments in the corresponding 1D curves of the 2D spectra
- Optional assignment of the existing NH₂ and OH peaks
- Automatically synchronize the 1D and 2D spectra processing modes
- Option to save the solvent tables, as well as the processing and the analysis parameters, for Automated Batch Verification
- Apply filters to only display the correlations representing the –H and –CH₃ groups attached to stereocenters in the NOE spectra
- Choose to display/hide the axis label for 1D spectra
- Directly calculate the HSQC-DEPT from the structural window
- Accommodation of large datasets (limited only by the user's Windows OS version)
Technique-Specific Features

Structure Elucidator Suite contains spectral processing capabilities for a variety of spectroscopic techniques.
- Processing and Analysis of LC/MS data with Structure Elucidator Suite
  Data Analysis
  - Independent control of chromatograms in hyphenated (LC/MS) datasets
  - Greater flexibility in data analysis and annotation of MSn spectra through independent control of individual spectral panes (undock MSn spectra as individual panes)
  - MSn component spectra are created automatically when a chemical structure is manually assigned to a component
  - Automatically calculate relative retention times
  Data Display
  - Undock MSn spectral panes for flexible visualization and review