Indanone DNA Building Blocks for Site-Specific Aldehyde Fluorescence

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing fluorescent molecular rotors (FMRs) for DNA sensing lack site-specific information and are prone to false readouts due to non-covalent attachment, and specialized covalent FMR probes are not commercially available, requiring specialized synthesis skills.

Innovation Solution

Development of indanone derivatives as nucleobase building blocks that can be covalently incorporated into DNA, forming fluorescent molecular rotors through aldol condensation, allowing for site-specific detection and enhanced fluorescence upon hybridization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If free cationic fluorescent molecular rotors are used for DNA sensing, then ease of use and commercial availability are improved, but site-specific information and reliability are worsened due to non-covalent attachment

Engineering Contradiction:

Improveease of useVSAvoidfalse fluorescent readouts

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The probe is divided into two functional segments: a fluorescent molecular rotor component and a nucleobase building block component. The nucleobase building block is incorporated covalently into DNA at specific positions, while the fluorescent molecular rotor is attached via a linker. This segmentation allows the probe to maintain site-specificity through covalent attachment while preserving the fluorescent sensing capabilities of the molecular rotor.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent merges the functions of a fluorescent probe and a nucleobase building block into a single integrated compound. The fluorescent molecular rotor is covalently linked to a nucleobase analogue that can be incorporated into DNA during synthesis, combining the fluorescent sensing function with the ability to provide site-specific information through covalent attachment to the DNA backbone.

Inventive Principle:

Principle #5Merging (Combining)

2Measurement precision

If covalent FMR probes are used for site-specific incorporation, then measurement precision and reliability are improved, but device complexity and ease of manufacture are worsened due to specialized synthesis requirements

Engineering Contradiction:

Improvesite-specific informationVSAvoidsynthesis expertise required

Core Design Contradiction:

Measurement precisionVSEase of manufacture

Solution Approach 1:

The nucleobase building block is designed to serve multiple functions: it acts as both a fluorescent probe and a DNA building block. The compound can be incorporated into DNA during standard solid-phase synthesis using conventional phosphoramidite chemistry, making it universally compatible with existing DNA synthesis protocols while providing site-specific fluorescent readouts.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent introduces an intermediary linker group that facilitates the connection between the fluorescent molecular rotor and the nucleobase building block. This intermediary structure enables covalent attachment to the DNA backbone while maintaining the fluorescent properties, serving as a mediator that simplifies the overall synthesis process.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Adaptability or versatility

If extended or isomorphic derivatives are used, then adaptability for different applications is improved, but device complexity increases due to multiple varieties

Engineering Contradiction:

Improveapplication-specific probesVSAvoidmultiple probe varieties

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies local quality by allowing different substituents and functional groups at specific positions within the nucleobase building block structure. The core structure remains consistent for covalent incorporation, while variable groups can be attached to provide different fluorescent properties and sensing capabilities for specific applications, such as detecting different metal ions or nucleic acid structures.

Inventive Principle:

Principle #3Local quality

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Provides site-specific fluorescent readouts with increased rigidity and reduced false signals, enabling efficient detection of nucleic acid hybridization and binding interactions.

Implementation Method 1

forming fluorescent molecular rotors through aldol condensation

Methodology Applied

Scientific EffectAldol condensation: Chemical Bonding

Implementation Method 2

enhanced fluorescence upon hybridization

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Implementation Method 3

increased rigidity and reduced false signals

Methodology Applied

Scientific EffectRigidity enhancement:

Data Source

PatentUS20260008796A1Indanone derivatives as nucleobase buildings block for on-DNA aldehyde capture

Publication Date: 2026.01.08 UNIVERSITY OF GUELPH

AI summary

The present disclosure relates to compounds of Formula (I) which are incorporated into DNA for on-DNA aldehyde capture and use as fluorescent molecular rotors.