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Indole Derivatives: Synthesis and Application III

Special Issue Editors


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Guest Editor
School of Chemistry, University of New South Wales (UNSW Sydney), Sydney, NSW 2052, Australia
Interests: heterocyclic chemistry; synthetic organic chemistry; natural products chemistry; new indole-based scaffolds; synthetic methodologies
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Special Issue Information

Dear Colleagues,

Indoles continue to generate new chemistry as a result of their potential for reactivity and their central role in biological chemistry through the involvement of tryptophan. This Special Issue therefore seeks to cover a broad range of interests, including new reactivity patterns, new methods for indole transformation, the synthesis of indoles with additional fused rings, new synthetic routes to the indole framework, indole–metal complexes, and aspects of medicinal chemistry incorporating indole systems. This Special Issue aims to be inclusive and to especially document new and unusual features of indole chemistry.

Prof. Dr. David StC Black
Prof. Dr. Naresh Kumar
Guest Editor

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Keywords

  • organic synthesis
  • natural products
  • heterocyclic compounds
  • ring cyclisations
  • metal complexes
  • organometallic compounds
  • polymers
  • molecular rearrangements
  • biological activity

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Published Papers (1 paper)

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Research

14 pages, 2575 KB  
Article
Synthesis and Characterization of 4-Indolylcyanamide: A Potential IR Probe for Local Environment
by Min You, Qingxue Li, Zilin Gao, Changyuan Guo and Liang Zhou
Molecules 2025, 30(20), 4063; https://doi.org/10.3390/molecules30204063 (registering DOI) - 12 Oct 2025
Viewed by 108
Abstract
This study reports the synthesis and comprehensive spectroscopic characterization of 4-indolylcyanamide (4ICA), a novel indole-derived infrared (IR) probe designed for assessing local microenvironments in biological systems. 4ICA was synthesized via a two-step procedure with an overall yield of 43%, and its structure was [...] Read more.
This study reports the synthesis and comprehensive spectroscopic characterization of 4-indolylcyanamide (4ICA), a novel indole-derived infrared (IR) probe designed for assessing local microenvironments in biological systems. 4ICA was synthesized via a two-step procedure with an overall yield of 43%, and its structure was confirmed using high-resolution mass spectrometry and 1HNMR. Fourier Transform Infrared (FTIR) spectroscopy revealed that the cyanamide group stretching vibration of 4ICA exhibits exceptional solvent-dependent frequency shifts, significantly greater than those of conventional cyanoindole probes. A strong linear correlation was observed between the vibrational frequency and the combined Kamlet–Taft parameter, underscoring the dominant role of solvent polarizability and hydrogen bond acceptance in modulating its spectroscopic behavior. Quantum chemical calculations employing density functional theory (DFT) with a conductor-like polarizable continuum model (CPCM) provided further insight into the solvatochromic shifts and suppression of Fermi resonance in high-polarity solvents such as DMSO. Additionally, IR pump–probe measurements revealed short vibrational lifetimes (~1.35 ps in DMSO and ~1.13 ps in ethanol), indicative of efficient energy relaxation. With a transition dipole moment nearly twice that of traditional nitrile-based probes, 4ICA demonstrates enhanced sensitivity and signal intensity, establishing its potential as a powerful tool for site-specific environmental mapping in proteins and complex biological assemblies using nonlinear IR techniques. Full article
(This article belongs to the Special Issue Indole Derivatives: Synthesis and Application III)
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