Photophysical properties of a series of 4-aryl substituted 1,4-dihydropyridines Ricardo Ferreira Affeldt a , Rodrigo Sebastian Iglesias b , Fabiano Severo Rodembusch a * and Dennis Russowsky a * In this article, a series of Hantzsch 1,4-dihydropyridines with different substituted aryl groups were synthesized and its spectral data obtained by UV–Vis absorption and fluorescence emission spectroscopies in solution. The dihydro- pyridines present absorption located around 350 nm and fluorescence emission in the blue–green region. A higher Stokes’ shift could be observed for the derivative 3b because of an intramolecular charge transfer in the excited state from the dimethylaniline to the dihydropyridine chromophores, which was corroborated by a linear relation of the fluorescence maxima (n max ) versus the solvent polarity function (Δf) from the Lippert–Mataga correlation. A comparison between the experimental data and time-dependent density functional theory-polarizable contin- uum model calculations of the vertical transitions was performed to help on the elucidation of the photophysics of these compounds. For these calculations, the S 0 and S 1 states were optimized using Becke, three-parameter, Lee–Yang–Parr/6-31 G* and Configuration Interaction Singles/6-31 G*, respectively. The predicted absorption max- ima are in good agreement with the experimental; however, the theoretical fluorescence emission maxima do not match the experimental, which means that the excited specie cannot be related to neither a locally excited state nor to an aromatized structure. Copyright © 2012 John Wiley & Sons, Ltd. Supporting information may be found in the online version of this paper. Keywords: aromatization; charge transfer; fluorescence; Hantzsch; NADH biomimmetics; oxidation photophysics; photophysics; time-dependent density functional theory; UV–Vis absorption; 1,4-dihydropyridines INTRODUCTION The 1,4-dihydropyridines, so called Hantzsch’ s esters are low molecular weight heterocyclic compounds described more than a century ago. [1] These compounds have been shown a wide-scope of biological activity and present a recognized capacity as calcium channel blockers, thus acting as vital drugs against heart diseases. [2,3] The dihydropyridine moiety (1,4-DHP) is common in many commer- cialized drugs (Scheme 1). Furthermore, the 1,4-dihydropyridines show other properties such as antioxidant, antiatherosclerosis, bronchodilator, antitumor, antidiabetic and neuroprotector properties, and are promising drugs for Alzheimer’ s disease treatment. [4] The 1,4-dihydropyridines are also known as biomi- metic analogues of the reduced form of nicotinamide adenine dinucleotide (NADH) hydrogen donor coenzyme system, bearing an oxidizable dihydropyridine core-based structure (DHP) connected to a p aromatic (p Ar ) system through an sp 3 carbon. [5] The classical Hantzsch synthesis involves multicomponent one-pot condensation of an aldehyde, ethyl acetoacetate and ammonia under reflux in alcoholic solvent, as presented in Scheme 2. [1,6] It is worth to mention that this methodology is associated with some disadvantages, such as long reaction times, harsh conditions and low product yields. However, because of its medicinal importance, the search for novel derivatives, improved reaction conditions and environmentally beneficial methods have been widely developed. [7–12] The photochemical oxidation and rearrangement mechanisms of the 1,4-dihydropyridines have already been studied. [13] These antihypertensive drugs, for example Nifedipine, are rapidly metabolized by oxidative mechanisms to dehydro-derivatives in human liver. [14] However, these compounds are highly sensi- tive to photo-oxidation and its photodegraded products may possess none or little biological activity. [15–17] Nifedipine decom- poses in UV light to give the aromatized 4-(2-nitrosophenyl)- pyridine homologue and in presence of oxygen, the nitroso group is reoxidized resulting in the 4-(2-nitrophenyl)pyridine ho- mologue (Scheme 3). [18–20] It is worth to mention that the nitroso product can be related to different biological applications. [21,22] The photochemical characterization of bioactive molecules is extremely relevant considering the light absorption and conse- quent modified pharmaco-dynamics, which results in unexpected efficiency of these drugs. [13] Although the fluorescence emission from the DHPs derivatives is well known, [23–26] no agreement * Correspondence to: Fabiano Severo Rodembusch and Dennis Russowsky, Instituto de Química, Departamento de Química Orgânica, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500. CEP 91501-970, Porto Alegre-RS, Brazil. E-mail: dennis@iq.ufrgs.br and rodembusch@iq.ufrgs.br a R. F. Affeldt, F. S. Rodembusch, D. Russowsky Instituto de Química, Departamento de Química Orgânica, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, CEP 91501-970, Porto Alegre, RS, Brazil b R. S. Iglesias Faculdade de Engenharia, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga 6681, CEP 90619-900, Porto Alegre, RS, Brazil Research Article Received: 5 July 2011, Revised: 8 December 2011, Accepted: 16 December 2011, Published online in Wiley Online Library: 2012 (wileyonlinelibrary.com) DOI: 10.1002/poc.2916 J. Phys. Org. Chem. (2012) Copyright © 2012 John Wiley & Sons, Ltd.