Björn Heitmann, Ph.D.

Applications Development

Pittsburgh – April 2016

The Smart Spectrometer

Innovation with Integrity

CMC-assist-

Summary NMR choices

When to run which experiment?

Researcher e.g. SmartDriveNMRRequests HSQC

Higher confidence

result

Structure Verification = SmartDriveNMR!

User approaches instrument with question, sample description and restraints

• Instrument decides which experiments to run with which parameters• Automatic data analysis • Yields result with confidence level ( - )• Decides if- and which other experiments are required to achieve user desired confidence level • If user allotted time permits, system sets up runs follow up experiments

Auto-result

withconfidence

level

OK

Automatic decision Auto-result II

OK

SmartDriveNMR: supported experiments

• More scans (better SiNo)• Analyzes data and determines if and how many scans are needed for improvement• If time permits, sets up and runs the experiment

• Suppression • Determines whether e.g. water suppression in DMSO-d6 would make sense and

determines required ns based on 1D1H

• HSQC• Determines if an HSQC would add more information and thus confidence • Based on the 1D1H determines required ns for HSQC

• HMBC • Determines how much more confidence would be gained by an HMBC • Based on the 1D1H determines required ns

• 13C• Determines if a 1D13C would add more information / confidence • Based on the 1D1H determines ns for 13C (not probe dependent yet)

SmartDriveNMR:Confidence on Structure verification

April 14, 2016 5

Definition of Confidence (C)

C = f ((ST, SQ)i, Complexity)

• ST: Spectrum type, e.g. 1H• SQ: Spectrum quality• Complexity of assignment problem

evaluated based on structure and n measured spectra (i=1 to n)

- Amount equi. atoms- Prediction quality- Spectrum overlap- Diversity in signals and atoms

• Desired Confidence is set as Stars in the GUI

• Confidence ranges between 0 to 5 Stars

• Confidence is calculated for the current verification project

Instrument decides which experiments to run

6April 14, 2016

There are three needed green lights to measure the next experiment:

1. Is another measurement useful?

2. Is enough time left?

3. Is the desired confidence not reached yet?

SmartDriveNMR: Setup in IconNMR

April 14, 2016 7

• Question at hand: structure verification

• Default SmartDriveNMR parameters are set in IconNMR

• One box to tick to activate SmartDriveNMR

• Set the default desired confidence the default maximum instrument time per sample

CMC-assist-

Summary SmartDriveNMR Results

Case Study: 1 / 4

9April 14, 2016

Expert: “Small and simple molecule with a nice and disperse spectrum – assignment straight forward” No follow-up experiment

SmartDriveNMR:1D 1H Consistent, Confidence 3.5 Stars No follow-up experiment

Final: Consistent, Confidence: 3.5 Stars

Case Study: 2 / 4

10April 14, 2016

Expert: “Small and simple molecule with an ok spectrum – assignment possible” maybe more Scans?

SmartDriveNMR:1D 1H Consistent, Confidence 2.8 Stars More Scans

Final: Consistent, Confidence: 3.2 Stars

Case Study: 3 / 4

11April 14, 2016

Expert: “Spectrum dominated by Water (and Solvent DMSO)” Suppression

SmartDriveNMR:1D 1H Consistent, Confidence 0.3 Stars Suppression

Final: Consistent, Confidence: 3.1 Stars

Case Study: 4 / 4

Expert: “Structure is complex and 1H spectrum is not easy to assign” HSQC

SmartDriveNMR: 1D 1H Consistent, Confidence 2.1 Stars HSQC

Final: Consistent, Confidence: 3.9 Stars

Expert: “Even though structure looks complex and worth an HSQC, the 1H spectrum is fairly easy to assign” No HSQC

SmartDriveNMR:1D 1H Consistent, Confidence 3.5 Stars No HSQC

Final: Consistent, Confidence: 3.5 Stars

M = 422 g mol-1

M = 520 g mol-1

SmartDriveNMR: HSQC statistics

When are HSQCs suggested:

• In 32% of > 1000 1D test cases (Ø 300 – 500 g/mol)

• More likely for high MW compounds

0%

20%

40%

60%

80%

100%

Ratio of suggested HSQCs on top of 1Dby MW

Summary

14April 14, 2016

• SmartDrive NMR carries out experiments automatically in an optimized way based on the previous experiment

• Optimization of spectrometer’s time while keeping best quality in results - saving user time “in front of the spectrometer”, e.g. day, night, week ends

• Both NMR experts and non expert benefit

• Interactive / Manual Structure Verification using CMC-assist 2.4

• SmartDriveNMR is new and available in TopSpin 3.5 fully integrated in Iconnmr - just a few clicks to try it !

Thank you!

Acknowledgements:

• Many NMR users, customers and colleagues for input, ideas and critics

• Come, see us for a demo

• … and we really appreciate your feedback!

Innovation with Integrity

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