Prof. Todor Deligeorgiev



The synthetic dye group specializes in the development of novel fluorescent nucleic acid probes and includes:

  1. Prof. Todor Deligeorgiev, PhD, DSc
  2. Assoc. Prof. Nikolai Gadjev,  PhD
  3. Assoc. Prof. Aleksey Vasilev, PhD
  4. Assistant Prof. Stefka Kaloyanova
  5. Doktorant Nedjalko Lessev


Nucleic acid molecules are the structural supports of genetic materials and therefore the key factors in many vital cellular processes. Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) encode biological information through their linear sequence of nucleotides to specify the composition of proteins, and through their shapes to control their assembly with other cellular macromolecules. Molecular biology and genetic engineering are based on DNA.

Fluorescence methods have a higher sensitivity than absorption methods, so they are often used to study nucleic acids. If a small molecular probe intercalates into the base pairs of a nucleic acid, the fluorescence spectrum of the probe will red shift and the fluorescence polarization will increase.

Contingent upon the different types of luminescent molecules, the fluorescent probes of nucleic acids are of five types: organic dyes, rare-earth ions, metal ion complexes, photochemical fluorescent compounds, and molecular beacon probes.

Studies on the binding of organic dyes with DNA are critical steps in the design of novel and more efficient drugs targeted at DNA and to explore the biological function of nucleic acids and the interaction mechanisms with some drugs

Intercalating dyes are in general aromatic cations with a planar structure that insert between stacked base pairs on the DNA duplex, thus providing an environmentally dependent fluorescence enhancement for the dye molecules, and creating a large increase in the fluorescence signal relative to the free dye in solution. The signal enhancement provides a proportional response, allowing direct quantitative DNA measurements.

In the last 20 years a novel class of nucleic acid probes based on intercalating cyanine dyes have been designed, synthesized and investigated. Such dyes have great sensitivity to nucleic acids and are used as consumables in various medical analyses, in bioimaging, in investigations of the bio processes on the molecular level etc.

We are one of the few groups in the world which has continuously worked in the field of intercalating fluorescent non-covalently binding nucleic acid probes for more than 15 years. We have synthesized many new representatives with even better properties than commercially-available products [1-3] and investigated the mechanism of fluorescence increase upon the binding of such dyes to DNA [4,5]. Our research interests also include the development of novel, more environmentally friendly, methods to prepare monomethine cyanine dyes and to improve known synthetic procedures  used to obtain intermediates.

In the future we intend to synthesize novel dyes with better properties for nucleic acid detection. We aim to synthesize dyes which are minor groove binders and which are suitable for rt PCR – a medical analysis method with ever-increasing applications.

In generally, there are two main factors that determine the high price of most detection methods, based on fluorescence:

- The price of the fluorescent probes – dyes and kits;

- The requirement for expensive light sources used to excite the fluorogenic molecules – lamps or gas and solid state lasers. Therefore, we believe that the main advantage will be the synthesis of a series of new symmetrical and asymmetrical monomethine cyanine dyes which absorb in the ultraviolet spectrum and can be excited by cheap light sources at 405 or 445 nm.

Bearing in mind that at present the commercially-available nucleic acid probes are very expensive and therefore not so accessible, we aim to synthesize nucleic acid fluorescent probes at a substantially lower price,  making such probes much more accessible. In the near future the demand for such dyes will be greater because cheaper analysis apparatus  is in development with cheap excitation light sources such as laser diodes and light diodes.  Such dyes will easily find applications in various fluorescent detection methods for bio-objects.


1. Todor G. Deligeorgiev, Nikolai I. Gadjev, Ilijana I. Timchiva, Vera A. Maximova, Haralambos E. Katerinopoulos, Evangelia Fukaraki, Synthesis of Homodimeric Monomethine Cyanine Dyes as Noncovalent Nucleic Acid Labels and Their Absorption and Fluorescence Spectral Characteristics, Dyes and Pigments, 44 (2) 131-136(2000).

2. T. Deligeorgiev, N. Gadjev, Il. Timtcheva, V. Maximova, Synthesis and properties of YOYO-1-type homodimeric monomethine cyanine dyes as noncovalent nucleic acid labels Dyes and Pigments  57(2) 161-164(2003).

3. Kovalska, V.B., Tokar, V.P., Losytskyy, M.Yu., Deligeorgiev, T., Vasilev, A., Gadjev, N., Drexhage, K-H., Yarmoluk, S.M., Studies of monomeric and homodimeric oxazolo[4,5-b]pyridinium  cyanine dyes as fluorescent probes for nucleic acid visualization68J. Biochem. Biophys. Methods 68(3), 155-165 (2006)

4. Furstenberg, A.; Julliard, M. D.; Deligeorgiev, T. G.; Gadjev, N. I.; Vasilev, A. A.; Vauthey, E., Ultrafast Excited-State Dynamics of DNA Fluorescent Intercalators: New Insight into the Fluorescence Enhancement Mechanism, J. Am. Chem. Soc.; 128(23); 7661-7669 (2006).

5. Alexandre Fürstenberg, Todor G. Deligeorgiev, Nikolai I. Gadjev, Aleksey A. Vasilev, Eric Vauthey, Structure-Fluorescence Contrast Relationship in Cyanine DNA Intercalators: Toward Rational Dye Design, Chem. -  Europ. J., 13( 30), 8600-8609 (2007).