Synthesis, photophysical characterisation and antimicrobial activity of a new anionic PAMAM dendrimer

Highlights

• A new photoactive PAMAM modified with 1,8-naphthalimides has been synthesized.

• Photophysical characteristics of dendrimer in different solvents have been determinate.

• Microbiological and cytotoxic activity of dendrimer have been investigated.

Abstract

A new anionic dendrimer (D1) has been synthesized and characterized by modification of a poly(amidoamine) (PAMAM) dendrimer with 3-(6-nitro-1,3-dioxo-1H-benzo[de]isoquinolin-2(3 H)-yl)propanoic acid (NI1). Its photophysical characteristics have been investigated in organic solvents of different polarity and a positive solvatochromism has been observed. The effect of the pH medium on the fluorescence intensity has been investigated and it has been shown that in the highly alkaline medium the dendrimer emits intense fluorescence. The dendrimer and its monomeric structural analogue have been loaded on a cotton fabric and the release of substances from the surface of the cotton fabric has been investigated. The compounds have been screened for antimicrobial and cytotoxic activities. They have been found more active against Gram-positive bacteria. The dendrimer exhibits slightly lower activity than the monomeric analogue, but is found to be significantly less cytotoxic. The deposited on cotton fabric D1 prevents the formation of bacterial biofilm on the fabric surface.

Introduction

Dendrimers are a relatively new class of hyperbranched macromolecules with unique chemical structure and functional characteristics [[1], [2], [3]]. The increased attention to this class of compounds arises from the fact that they are a new form of organization of polymeric materials, the peculiarity of which is the combination of the properties of low molecular weight and high molecular weight substances. Compared to the small molecules and linear polymers with antimicrobial properties, dendrimers have the potential of a single molecule to carry a large dose of biologically active substance. In addition, dendrimer biocides are characterized not only by increased activity but by reduced toxicity, as well [4]. Dendrimers contain a large number of functional groups in the branches and in the periphery, which gives great opportunities for purposeful modification of their properties. The first one enables their binding to the functional groups of different matrix (for example textile materials). The second one allows multiple copies of a drug to unite in one molecule. This may induce a multivalent effect, reminiscent of the polyvalent interactions widely occurring in biological systems [2].

Functionalization of dendrimers with photoactive groups expand their application fields [5]. The chemical structure of the dendrimer molecules makes them relevant for different application in such fields as biomedicine, nanomedicine ecology, etc. [[6], [7], [8], [9], [10], [11], [12]]. Cationic or anionic dendrimer structures can be obtained by suitable chemical methods. They exhibit high antimicrobial activity against different pathogens [[13], [14], [15], [16], [17]]. Some of them have more pronounced activity to Gram-positive bacteria, while others are more active against Gram-negative bacteria.

The utilisation of antibacterial textiles in daily life, and especially in hospital and clinical practice, may prevent various diseases and bacterial infections. The production of antibacterial textiles is mainly achieved by treating textile materials with biologically active substances [[18], [19], [20], [21]]. These substances can be attached to the surface of the textile materials through different interactions depending on their application.

In our laboratory we conduct systematic studies on the modification of dendrimers with 1,8-naphthalimide [[22], [23], [24], [25]], acridine [26], benzanthrone [27,28], or 4-nitrobenzofurazan [29] with the aim of investigating the structure - properties relationship. These dendrimers have been probed as metal and/or pH detectors. In the last few years, our efforts have also been focused on the antimicrobial and anticancer activity of such systems [[30], [31], [32], [33], [34]]. This direction was dictated by the fact that pathogenic microorganisms are becoming more resistant to the antibiotics used in medical practice, which requires the search and study of new compounds with increased antimicrobial activity [35].

Derivatives of 1,8-naphthalimides are cyclic imides, characterized by hydrophobicity and large π-fused skeleton, which can easily interact with various biological systems through non-covalent interactions, such as π-π stacking. This determines the wide biological and biomedical interest to them [[36], [37], [38]].

This study aims to investigate a new anionic PAMAM dendrimer, peripherally modified with four 1,8-naphthalimide units. The basic photophysical characteristics of the dendrimer have been investigated in organic solvents of different polarity. The effect of pH has also been investigated. The antimicrobial activity of the dendrimer against different pathogens has been examined in a liquid medium and after deposition on a cotton fabric. By gaining insight into the factors that correlate with dendrimer structure one can design and further optimize their properties for various applications. A computer simulation technique (DFT calculations) has been used to predict some properties of the new PAMAM dendrimer (and to differentiate them from those of the 1,8-naphthalimide derivative, used for its peripheral functionalization) at the molecular level. DFT-based calculations provide valuable information about the configuration and conformation of the molecules and important insights into the electronic structure. To understand the relationship between electronic structure and photophysical behaviour, we have investigated theoretically (by means of popular and affordable DFT method) the 1,8-naphthalimide derivative and a model system, representing the studied new PAMAM dendrimer.