[Paper Review] Determining Molecular Complexity using Assembly Theory and Spectroscopy

Michael Jirásek, Abhishek Sharma+10 more|arXiv (Cornell University)|Feb 24, 2023

Mass Spectrometry Techniques and Applications10 citations

TL;DR

The paper presents an experimental approach to estimate molecular complexity (assembly index, MA) from spectroscopic data (NMR, MS/MS, IR), aligning with assembly theory to enable rapid, intrinsic complexity assessment even in mixtures.

ABSTRACT

Determining the complexity of molecules has important applications from molecular design to understanding the history of the process that led to the formation of the molecule. Currently, it is not possible to experimentally determine, without full structure elucidation, how complex a molecule is. Assembly Theory has been developed to quantify the complexity of a molecule by finding the shortest path to construct the molecule from building blocks, revealing its molecular assembly index (MA). In this study, we present an approach to rapidly and exhaustively calculate the MA of molecules from the spectroscopic measurements. We demonstrate that molecular complexity (MA) can be experimentally estimated using three independent techniques: nuclear magnetic resonance (NMR), tandem mass spectrometry (MS/MS), and infrared spectroscopy (IR), and these give consistent results with good correlations with the theoretically determined values from assembly theory. By identifying and analysing the number of absorbances in IR spectra, carbon resonances in NMR, or molecular fragments in tandem MS, the molecular assembly of an unknown molecule can be reliably estimated from experimental data. This represents the first experimentally quantifiable approach to defining molecular assembly, a reliable metric for complexity, as an intrinsic property of molecules and can also be performed on complex mixtures. This paves the way to use spectroscopic and spectrometric techniques to unambiguously detect alien life in the solar system, and beyond on exoplanets.

Motivation & Objective

• Motivate the need for an experimentally measurable molecular complexity metric beyond full structure elucidation.
• Introduce Assembly Theory as a way to quantify complexity via the shortest construction path from building blocks (MA).
• Propose spectroscopic methods to exhaustively and rapidly estimate MA from experimental data.
• Demonstrate consistency between experimental MA estimates and theoretically computed MA values.
• Highlight potential applications in detecting alien life and analyzing complex mixtures.

Proposed method

• Define molecular assembly index (MA) from Assembly Theory as the minimal steps to assemble a molecule from building blocks.
• Develop procedures to estimate MA from spectroscopy data: IR absorbances, NMR carbon resonances, and MS/MS fragments.
• Show that three independent techniques yield consistent MA estimates that correlate with theoretical MA values.
• Apply analysis to unknown molecules to infer their molecular assembly from experimental measurements.

Experimental results

Research questions

• RQ1 Can MA be experimentally estimated from spectroscopy data without full structure elucidation?
• RQ2 Do IR, NMR, and MS/MS provide consistent MA estimates that correlate with theoretically computed MA?
• RQ3 Can MA be reliably determined for unknown molecules and complex mixtures using spectroscopic measurements?
• RQ4 What is the potential of MA-derived complexity as a tool for detecting extraterrestrial or extrinsic chemical origins?

Key findings

• MA can be experimentally estimated using NMR, MS/MS, and IR with good correlation to theoretical MA values.
• Identifying and analyzing IR absorbances, carbon resonances in NMR, or molecular fragments in MS/MS can yield reliable estimates of molecular assembly.
• All three spectroscopic techniques produce consistent MA estimates, supporting MA as an intrinsic property of molecules.
• The approach enables MA estimation in complex mixtures rather than requiring complete structure elucidation.
• This work establishes a first experimentally quantifiable approach to defining molecular assembly and its use in detecting alien life scenarios.