On the Cooperativity Effect in Watson and Crick and Wobble Pairs for

Subscriber access provided by Kaohsiung Medical University

Article

ON THE COOPERATIVITY EFFECT IN WATSON&CRICK AND WOBBLE PAIRS FOR A HALOURACIL SERIES AND ITS POTENTIAL QUANTITATIVE APPLICATION STUDIED THROUGH SERS Mónica Mamián-López, and Marcia L.A. Temperini Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.8b02188 • Publication Date (Web): 20 Nov 2018 Downloaded from http://pubs.acs.org on November 20, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Analytical Chemistry

ON THE COOPERATIVITY EFFECT IN WATSON&CRICK AND WOBBLE PAIRS FOR A HALOURACIL SERIES AND ITS POTENTIAL QUANTITATIVE APPLICATION STUDIED THROUGH SERS Mónica B Mamián-López1*, Marcia L. A. Temperini1 1Department

of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, São Paulo-Brazil.

ABSTRACT: The nature of the cooperativity effect of hydrogen bonds in Watson & Crick and wobble base pairs formed with thymine, uracil and its 5-halogenated derivatives (5-fluoro, -chloro and -bromouracil) have been studied through SERS, and using chemometric tools to process data and extract relevant information. Remarkable differences between the two kinds of pairs were clearly observed and the behavior correlated to the withdrawing character of different substituents at the 5- position of uracil was verified. Multivariate analyses have also unveiled information about pair’s stability and a stronger cooperativity effect seems to rule the Watson & Crick pairs when compared to wobble pairs. Defined patterns in the behavior of Watson & Crick pairs allowed the design of an indirect methodology for quantifying 5-bromouracil using a PLS method with variable selection. LOD values of 0.037 and 0.112 mmol L-1 in absence and presence of structurally similar interferences were reached, while its direct SERS quantification is only possible at around 45 mmol L-1.

INTRODUCTION Despite of being known as a weak chemical interaction, the hydrogen bond plays an essential role in the arrangement of the molecules that supports all life forms: the nitrogenous bases adenine, guanine, cytosine along with thymine in the DNA and uracil in the RNA. Those bases are paired in a canonical way that follows the Watson & Crick (W&C) rules1 resulting in the formation of the W&C pairs, interacting in a selective fashion between a purine and a pyrimidine: adenine-thymine (A-T), guanine-cytosine (G-C) for DNA and adenine-uracil (A-U) for RNA. As the stacking interactions of the double helix are “noninformational”, just stabilizing the structure, the hydrogen bonds are “informational”, i.e. responsible by the high fidelity of DNA synthesis and the RNA transcription from the gene2. Analogously to the W&C pairs but with different characteristics, the formation of mismatched or wobble pairs in both DNA and RNA (G-T and G-U, respectively) is observed. In DNA the high precision of the replication process can be affected by errors causing mispairing of the nitrogenous bases3.This knowledge has allowed the development, for example, of drugs with mutagenic properties such as the halouracil derivatives (5XU), 5-fluoro, 5-chloro and 5-bromouracil (5-FU, 5-ClU, 5BrU)4, compounds that have received increasing interest in the last 20 years thanks to their biological and pharmaceutical importance5,6. Besides their application as antibacterial, antiviral and antitumor agents, the 5-ClU and 5-BrU seems to be strongly involved in inflammatory processes related to cancer development7. Various studies have shown strong evidences of halogenation processes

occurring during inflammation of human tissues, targeting the nitrogenous bases and producing mainly 5-ClU and 5BrU. The reactions producing these species in living organisms are mediated by enzymes favoring the halogen oxidation to HOCl (or HOBr) and the ulterior uracil halogenation following highly specific processes8,9. It has been observed that the introduction of 5halouracils in the place of thymine provides enhanced photosensitivity to UV radiation retaining DNA’s in vivo activity10-12 in modified E. Coli bacteria. In a similar way, the wobble pairs have a main role in the formation of complexes with proteins by supplying specific sites for recognition of proteins or ligands such as ions or antibiotics. Several studies focused toward a better comprehension of the hydrogen bond in the DNA and RNA bases are continuously being developed but the main and necessary condition -and limitation at the same time- for these particular systems is that studies should be performed in aqueous medium and using a technique sensitive enough to detect those species in concentration values below their very low solubility, conditions not so easy to be fulfilled. An important share of the research on this topic is based on theoretical calculations13-16 and techniques such as NMR with isotopic labelling or MS analyses. For detection purposes, techniques such as chromatography and electrochemistry/spectroelectrochemistry have also been used17,18. Despite Raman spectroscopy19 supplies high amount of structural information from nitrogenous bases as widely found in literature, its low cross section, and the low

ACS Paragon Plus Environment

Analytical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

solubility in water, makes it not suitable for studying those compounds under the in vivo conditions. Introducing nanostructured metallic surfaces for intensifying the Raman spectra, i.e. SERS (Surface Enhanced Raman Spectroscopy) technique20, is an excellent strategy since its responses are as information-rich as in Raman spectra but gaining a drastic lowering in the limit of detection (LOD) values, thus surpassing the solubility barrier.

(R=H), 5-XU(R=F, Cl or Br), b. adenine, c. guanine, d. W&C pairs and e. wobble pairs.

METHODS. Reagents and solutions. Chloroauric acid (HAuCl4) 98 wt%, guanine (C5H5N5O), 98 wt%,, adenine (C5H5N5), 99.6%, thymine (C5H6N2O2) 99.6%, 5-fluorouracil (C4H3FN2O2) , 99 wt%, 5-chlorouracil (C4H3ClN2O2) , 99 wt%, 5-bromouracil (C4H3BrN2O2) , 98 wt%, anhydrous sodium citrate and sodium chloride were purchased from Sigma-Aldrich. MilliQ water was used for all solutions and all of them were sonicated for 15 min to aid dissolution.

The affinity of nitrogenous bases by metal nanoparticles is well known and, particularly on gold nanoparticles, their affinity follows the increasing order T, U «« G ~ A21, where T, U and its analogues show a particularly low affinity. Regarding to its interaction with metallic surfaces, a particular behavior involving an interaction known as hydrogen-bond cooperativity has been observed. Here, thymine is coadsorbed along with the A on gold electrodes and its characteristically very low SERS signal is considerably enhanced22. This observation has been explained as a result of a planar orientation that would cause an increasing in the effective concentration of A on the surface and a nearly parallel orientation of T after their interaction23. Besides, this enhancement has been proved to be useful as a way to drastically diminish its LOD value24.

Gold nanoparticles synthesis. Semi-spherical gold nanoparticles (AuNPs) have been synthesized following an experimental modification27of the Lee–Meisel method28. Briefly, a 0.05 mmol per L HAuCl4 aqueous solution was prepared in 95 mL of milli-Q water and boiled under constant stirring. Then, 3.0 mL of a 1% (by mass) sodium citrate solution has slowly been added to the boiling solution under stirring. Once the solution turned red, stirring and heating were stopped and after reaching room temperature, the total volume was brought to 100 mL. Finally, the colloidal suspension was activated with NaCl 0.10 mol L-1 by adding 50 µL to 5.0 mL of colloid.

Following these observations and considering the utmost importance of the W&C and wobble pairs itself, and its promissory application as an analytical route for significantly diminishing the LOD values of uracil and derivatives, our work lies on the application of SERS technique over nanostructured colloidal gold assisted by chemometric approaches to study the behavior of 5-FU, 5ClU and 5-BrU when pairing with either A or G as shown in Fig 1. Besides, based on those results, this work evaluates how the cooperativity effect could allow quantitative determination of 5-BrU in concentration levels similar to those expected in human plasma or urine still in presence of its analogous compounds as interferences.

Mixtures. Mixtures containing from 1 to 5 compounds (T, U, 5-FU, 5-ClU, 5-BrU) were prepared and then separately mixed with A and G to form their respective W&C or wobble pairs. Mean concentrations value for each species was 3.0 mmol L-1 and their corresponding molar fraction (χ) values are depicted in Fig. 2 (Additional details in SI section and Table S1).

This is the first report using the high specificity and sensibility of SERS technique to study the behavior of hydrogen bonds in W&C and wobble pairs at very low concentrations in aqueous media. At the same time it contributes to research focused on direct sensing of DNA bases and related compounds considering the increasing interest in this area is strengthening the already powerful analytical possibilities of SERS25,26. 10

10O

11R 5 6

3

4

N

2

NH

NH

O8

1

H

NH 2

R

N

d.

NH

N3

N 3

NH

7

3

NH NH2

c.

10

H2N N

N

O

6

10 H

N1

3N H

N1

b.

a.

O

7N

6

7

NH

Figure 2. Molar fraction of binary (M1-M10), ternary (M11-M19), quaternary (M20-M24) and five-component (M25) mixtures.

13O

NH2

O

H

N 3

R

O

N

N

2

NH

6

H

NH

13

O

e.

N 7

Figure 1. Molecular structures of a. thymine (R=CH3), uracil

Page 2 of 10

Quantitative determination. Aqueous solutions of 5BrU between 0.00 and 5.80 mmol L-1 were prepared from a stock solution of 6.50 mmol L-1. For determination of LOD values without interferences, aliquots of 100 µL of each solution were mixed with 100 µL of adenine 0.06 mmol L-1 to form W&C pairs. Similar experiments were carried out with solutions of 5-BrU in presence of 5-FU (4.5 mmol L-1) and 5-ClU (5.20 mmol L-1). Spectral acquisition and data processing. SERS spectra were obtained using a Renishaw inVia confocal microscope equipped with a 785 nm laser and a 20X longworking distance objective lens. Exposure times of 10 s and 5% of laser power (500 mW max) was applied for all measurements. Each spectrum was acquired by mixing the colloidal gold with sample solution in a 5:1 volume ratio.


Page 3 of 10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Data processing was performed in Matlab 8.1.0.604 (R2013a). MCR-ALS analysis was accomplished using the freely available toolbox developed by R. Tauler29. The Singular Value Decomposition (SVD) and Simple-to-use Interactive Self Modelling Analysis (SIMPLISMA) algorithms were used embedded in the MCR-ALS toolbox. Calculations were constrained with no negativity in spectra and concentrations in all cases.

noticeable, followed by the band at 1074 cm-1 mode (-C-Br) and the mode at ca. 1660 cm-1 (carbonyl) whose electron density is directly associated to the aromatic system. The particular enhancement of these modes follows a probably reorienting process induced by the A moiety that seems to highly influence the π- interaction of the aromatic ring with the metallic surface reached through a flat orientation as previously evidenced by Rueda et.al22.

PLS and iPLS models were carried out using the PLS Toolbox 8.5.2 (2017) by Eigenvector Research, Inc. Data were pre-processed with a smoothing procedure (5 pt window) and a Whittaker filter (λ=100, ρ=0.001) to correct baseline.

RESULTS SERS spectra of halouracils and its respective W&C and wobble pairs. SERS responses for 5-FU, 5-ClU and 5-

BrU were registered for stock solutions of 5.60, 5.03 and 6.52 mmol L-1(see Fig S1). Due to its low affinity to AuNPs, these spectra require more drastic experimental conditions, different to those applied along this study (See SI section for details). Thus, laser power and number of accumulations were increased in order to observe the main bands (notice the maximum intensity in the spectra). The SERS spectra of 5XU are intensified by pairing with A. In Fig. 3a the 5-BrU SERS spectrum presents lower band intensities than the corresponding bands in the 5-BrU/A SERS spectrum, Fig 3c. For comparison purposes the spectrum of A itself is present in Fig. 3b. The bands corresponding to each species are shown in different colors. Main bands assignments are based on literature calculations and experimental results previously reported30-32. Although spectra for 5-ClU and 5-BrU are more similar than that of 5-FU, all of them present common spectral features. Only bands for the 5-BrU spectrum will be assigned (The spectra of 5-FU and 5-ClU are shown in Fig S1). Representative bands for the other two 5-XU are tentatively assigned (See Table S2. Main bands of G (wobble pairs), T and U were also included for comparison. No band shifts were observed for any 5-XU when their respective W&C and wobble pairs were compared. Characteristic features for this series of compounds are the ring breathing in-plane vibration, that varies slightly across the series between 786 and 800 cm-1 , being located at 793 cm-1 for 5-BrU, and the in-plane bending band at ca. 998 cm-1, also related to in plane ring vibration (C5C6N1). Bands around 570 and 1623 cm-1 are assigned to bending (O10C4N3) and stretching modes (O10C4, O8C2) of carbonyl groups respectively. It is worth mentioning that the band observed at 1074 cm-1 is calculated as corresponding to the –C-Br stretching mode30. Bands marked with green are specific of A with its main peaks located at 735 (in-plane symmetric ring breathing), 967 (NH2 rocking), 1223 (ring -C-C- stretching) and 1467 cm-1 (CH3 deformation).

Figure 3. SERS spectra of a. 5-BrU (magenta), b. adenine (green) and c. 5-BrUW&C pair (blue).

Affinity behavior and limits of detection of 5-XU in its W&C and wobble pairs. A first step on the affinity of the studied series to the AuNPs is the estimation of their individual LOD values (no pair formation involved). This figure of merit was estimated by calculating the standard deviation (SDblank) of 5-XU/AuNPs’ spectrum and determined following equation 1: LOD=3.3SDblank

(1)

To accomplish this, SERS spectra were registered for each compound (thymine, uracil, 5-XU (X=F, Cl and Br) and to calculate the SD value was used the band corresponding to the in-plane ring breathing as shown in the Fig. 4 (insets), located around ca. 790 cm-1. LOD values were 22.0 (thymine), 28.4 (uracil), 18.9 (5-FU), 16.5 (5-ClU) and 14.8 (5-BrU) mol L-1, where a trend in their affinity is already evidenced, and that seems to accompany the size of the substituent at position 5, at least from an univariate approach (See the SERS spectra for wobble pairs in Fig S2).

When W&C pairs are formed, a strong intensification of the band at 793 cm-1 (symmetric ring breathing) is



Page 4 of 10

dominated by G (663 cm-1) at any value of χ for any compound. Particularly, all samples having 5-BrU are located far from G and at negative values of PC2, i.e. driven by this species, showing already that its SERS activity seems to strongly predominate even when it forms either W&C or wobble pairs. At this point, it is already clear a difference in the SERS behavior between W&C and wobble pairs and the increasing size and withdrawing character in the halogen substituent seems to strongly influence those observations. Also it is possible to consider that since W&C pairs are more dispersed on the PC2, its formation would work better for quantitative purposes than with wobble pairs since it seems that a higher discrimination among spectra can be reached. Figure 4. SERS spectra of W&C pairs of T, U, XU(X=F, Cl and Br). Inset: in-plane ring breathing mode.

With these results as a reference, exploratory analyses using PCA (Principal Component Analysis) were carried out for the spectra of both W&C and wobble pairs mixtures in order to visualize possible patterns associated to the kind of pairing being formed, giving as a main result the scores and loading plots in Fig. 5.

In order to confirm this and to get a better understanding of the W&C pairs behavior, separate PCA analysis were carried with samples labelled according to the 5-XU species being evaluated. For example for W&C pairs containing 5-BrU (analogous labelling was used for all species): (i) W&C mixtures containing 5-BrU at any value of χ (≠0); (ii) W&C mixtures with thymine, uracil, 5-XU(X=F, Cl, except Br); (iii) W&C pair of 5-BrU (χ=1); (iv)Adenine.

Figure 6. Scores (top) and loadings (bottom) plots for W&C pairs of thymine, uracil and its analogous XU(X=F, Cl and Br). Figure 5. Scores plot for PC1 and PC2 for SERS spectra of W&C and wobble bases pairs.

A clear difference in the behavior between the two types of pairing is detected. For the W&C pairs, 3 to 4 subclasses increasing its distance from the A (red diamonds) accompanying the increasing size of the substituent on the position 5 (and also its electron withdrawing ability), were observed. The PC1 loadings confirms that samples located at the far right on this PC are being dominated mainly for the ring breathing band of A (735 cm-1) and lose this influence when the substituent goes from –CH3 to Br. Just reinforcing, samples on the negative region on PC2 are governed by two main features of the 5-BrU, the ring breathing and Br-C stretching (793 and 1074 cm-1). On the contrary, for wobble pairs, only 2 groupings are distinguishable and about the 80% of samples are still

The first noticeable characteristic in the scores plot (Fig. 5, top), is a very clear pattern in the samples containing 5BrUW&C where all samples containing it (χ=(0,1]) are grouped following the positive values of PC1 corresponding mainly to the band at 793 and 1070 cm-1 (green strips), very specific for this compound. The rest of variables on PC1(+) belongs to both A and 5-BrU backbone and the commonly most intense A band (732 cm-1, red strip) has a very discrete contribution for this group. Although 5-FUW&C samples are following the PC2 on the negative side, the loadings for this component has a contribution of the ring breathing and carbonyl stretching modes of both 5-FU and thymine (blue strips) indicating a similar affinity albeit a clear discrimination is not possible. For the 5-ClU case and, except for a small subgroup located close to 5-ClUW&C, the rest of the samples containing it, seems not following a


Page 5 of 10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


trend. Besides, for 5-ClU case, a not very conclusive pattern is observed only when the PC3 is included, confirmed by its corresponding loadings with high influence of 796 cm-1 ring breathing and carbonyl stretching bands (yellow strips). As A spectra are strongly driven by the positive loadings of PC2, highly specific to this nucleobase (red strips), and considering the absence of samples located close to it, is easily established that, firstly, despite A exerts a high intensification of signals of the compounds studied, the SERS spectra of W&C pairs are receiving a major contribution of the vibrational modes of its paired compound. In spite of the larger probability of finding πstacked structures in aqueous solutions33,34 our observations don’t seem to evidence a direct interaction of these species with AuNPs, since, if the SERS spectra were coming from π-stacked structures, this would imply in the interaction occurring through one of the molecules, probably the one with higher affinity toward AuNPs, adenine in our case. Thus, the ring “breathing” mode from the 5-BrU would not be observable or enhanced as notoriously as in our spectra. Even if the π-stacked molecules were both perpendicular to the surface, the spectral profile would be completely different, at least not dominated by the ring “breathing” mode35. Moreover, we already showed that the –C=O band, present only in the halouraciles is being always enhanced, meaning that we are detecting this species, despite its very low affinity toward AuNPs. This observation also disagrees with a π-stacking arrangement and reinforces our argument about the formation of the base pairs via hydrogen bonds. As we will show later, this does not affect a quantitative approach. In second place, the results show that the affinity of W&C pairs toward AuNPs follows the order TW&C ~ UW&C < 5FUW&C < 5-ClUW&C94%) with the spectra of the pairs allowing establishing crucial differences on their interaction with AuNPs. Using the cooperative effect of the hydrogen bonds as a strategy for enhancing the Raman signals of thymine, uracil and its halogenated analogous gives a novel possibility of quantitative application, solving the low-affinity toward AuNPs problem. The behavior of the W&C pairs and the possibility of digitally isolate its respective SERS responses makes possible to modelling it against concentration. In addition, given that the PLS method allows modelling in presence of interferences, a property known as second-order advantage, the methodology would be applicable to more complex samples, for example urine, tissues or plasma where these 5-XU are important biomarkers.

Table 1. Figures of merit for the iPLS models for quantification of 5-BrU in absence and with 5-FU and 5-ClU as interferents. Methodology

Instrumental

Interferences

RMSECVa

RMSEPb

conditions Direct determination

50 % lpc, 10 accumulations

W&C pairing

5% lp, 1 accumulation

LOD

LOQ

(mmol L-1)

(mmol L-1)

No

____

____

14.8d

44.85 d

No

0.243

0.290

0.037

0.111

5-FU, 5-ClU

0.231

0.340

0.112

0.338

(10 s each) (10 s)

W&C pairing

5% lp, 1 accumulation (10 s)



Page 8 of 10

a.RMSECV

(Root mean square error of cross-validation, b RMSEP (Root mean square erro of prevision), c lp=laser power (max= 500 mW), d approximate values, calculated with SD value for a blank.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Experimental details, complimentary SERS spectra of 5-halouracils, alpha values for 5-halouracils and guanine; extinction spectra, MCR complimentary information, bands assignment for nitrobases and 5-halouracils (file type: pdf)

AUTHOR INFORMATION Corresponding Author * E-mail: [email protected]. Present address: Center for Natural and Human Sciences, Federal University of ABC, São Paulo – Brazil. Author Contributions The manuscript was written through equal contributions of all authors and final approval has been given.

ACKNOWLEDGMENTS The authors are thankful to CNPq (Grants 154066/2016-8 and 302792/1015-5) and FAPESP (Grant 2016/21070-5, 2014/078413).

REFERENCES Watson, J.D.; Crick, F. H. C. Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid. Nature 1953, 171, 737-738. 2 Goodman, M.F. Hydrogen bonding revisited: Geometric selection as a principal determinant of DNA replication fidelity. Proc. Natl. Acad. Sci. 1997, 94, 10493-10495. 3 Holley, R.W.; Apgar, J.; Everett, G.A.; Madison, J.T.; Marquisee, M.; Merrill, S.H.; Penswick, J.R.; Zamir, A. Structure of a Ribonucleic Acid Science, 1965, 147, 1462-1465. 4 Brovarets, O.O. Mutagenic properties of 5-halogen derivatives of uracil:quantum-chemical investigation. Ukr. Bioorg. Acta, 2012, 1724. 5 Salimgareeva, M.Kh.; Farafontova, E.I.; Abdrakhimova, G.S.; Ivanov, S.P.; Vakhitova, Y.V. Synthesis, Biological Activity, and Mechanism of Action of Mono-Substituted 5-Halouracil Salts. Pharm. Chem. J. 2014, 48, 235-237. 6 Grem, J.L. 5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. Invest New Drugs, 2000, 18, 299-313. 7 Henderson, J.P.; Byun, J.; Takeshita, J.; Heinecke, J.W. Phagocytes produce 5-chlorouracil and 5-bromouracil, two mutagenic products of myeloperoxidase, in human inflammatory tissue. J. Biolog. Chem. 2003, 278, 23522–23528. 8 Whiteman, M.; Spencer, J.P.E.; Jenner, A.; Halliwell, B. Hypochlorous Acid-Induced DNA Base Modification: Potentiation by Nitrite: Biomarkers of DNA Damage by Reactive Oxygen Species. Biochem. Biophys. Res. Comm. 1999, 257, 572-576. 9 Liu, P.; Theruvathu, J.A.; Darwanto, A.; Lao, V.V.; Pascal, T.; Goddard III, W.; Sowers, L.C. Mechanisms of base selection by the Escherichia coli mispaired uracil glycosylase. J. Biol. Chem. 2008, 283, 8829-8836. 0 Marlière P.; Patrouix J.; Döring V.; Herdewijn P.; Tricot S.; Cruveiller S.; Bouzon M.; Mutzel R. Chemical evolution of a bacterium's genome. Angew. Chem. Int. Ed. 2011, 50, 7109-7114.

1 Acevedo-Rocha, C.G.; Budisa. N. On the Road towards Chemically Modified Organisms Endowed with a Genetic Firewall. Angew. Chem. Int. Ed. 2011, 50, 6960 - 6962. 12 Rak, J.; Chomicz, L.; Wiczk, J.; Westphal, K.; Zdrowowicz, M.; Wityk, P.; Zyndul, M.; Makurat, S.; Golon, L. Mechanisms of Damage to DNA Labeled with Electrophilic Nucleobases Induced by Ionizing or UV Radiation. J. Phys. Chem. B 2015, 119, 8227-8238. 3 Fonseca-Guerra, C.; Bickelhaupt, F. M.; Snijders, J.G.; Baerends, E.J. The Nature of the Hydrogen Bond in DNA Base Pairs: the Role of Charge Transfer and Resonance Assistance. Chem. Eur. J. 1999, 5, 3581-3594. 4 Portalone, G.; Moilanen, J.O.; Tuononen, H.M.; Rissanen, K. Role of Weak Hydrogen Bonds and Halogen Bonds in 5-Halo-1,3dimethyluracils and Their Cocrystals—A Combined Experimental and Computational Study. Cryst. Growth Des. 2016, 16, 2631−2639. 5 Guerra, C.F.; Bickelhaupt, F.M.; Baerends, E. Hydrogen Bonding in Mimics of Watson-Crick Base Pairs involving C–H Proton-Donor and F Proton-Acceptor Groups. A Theoretical Study. J. Chem. Phys. Chem. 2004, 5, 481- 487. 6 Harroun, S.G. The Controversial Orientation of Adenine on Gold and Silver. Chem.Phys.Chem. 2018, 19, 1003-1015. 7 Cooke, M.S.; Olinski, R.; Loft, S. Measurement and meaning of oxidatively modified DNA lesions in urine. Cancer Epidemiol Biomarkers Prev. 2008, 17, 3-14. 18 Akay, S.; Kayan, B.; Yang, Y. Solubility and Chromatographic Separation of 5-Fluorouracil under Subcritical Water Conditions. J. Chem. Eng. Data 2017, 62, 1538−1543. 19 Raman, C.V.; Krishnan, R.S. A new type of secondary radiation. Nature 1928, 121, 501-502. 20 Aroca, R.; Bujalski, R. Surface enhanced vibrational spectra of thymine. Vib. Spectrosc. 1999, 19, 11-21. 21 Liu, J. Adsorption of DNA onto gold nanoparticles and graphene oxide: surface science and applications. Phys. Chem. Chem. Phys. 2012, 14, 10485-10496. 22 Rueda, M.; Prieto, F.; Álvarez-Malmagro, J.; Rodes, A. Evidences of adenine–thymine Interactions at gold electrodes interfaces as provided by in-situ infrared spectroscopy. Electrochem. Comm. 2013, 35, 53–56. 23 Alvarez-Malmagro, J.; Rueda, M.; Prieto, F. Electrochemical Impedance Spectroscopy study of the adsorption of adenine on Au (111) electrodes as a function of the pH. J. Electroanal. Chem. 2017, 793, 209-217. 24 Mamián-López, M.B.; Corio, P.; Temperini, M.L. Cooperative hydrogen-bonding of the adenine–thymine pair as a strategy for lowering the limit of detection of thymine by surface-enhanced Raman spectroscopy. Analyst 2016, 141, 3428-3436. 25 Garcia-Rico, E.; Álvarez-Puebla, R.A; Guerrini, L. Direct surfaceenhanced Raman scattering (SERS) spectroscopy of nucleic acids: from fundamental studies to real-life applications. Chem. Soc. Rev. 2018, 47, 4909–4923. 26 Zong, C.; Xu, M.; Xu, L-J.; Wei, T.; Ma, X. ; Zheng, X. S.; Hu, R.; Ren, B. Surface-Enhanced Raman Spectroscopy for Bioanalysis: Reliability and Challenges. Chem. Rev. 2018, 118, 4946-4980. 27 Mamián-López, M.B.; Poppi, R.J. Standard addition method applied to the urinary quantification of nicotine in the presence of cotinine and anabasine using surface enhanced Raman spectroscopy and multivariate curve resolution. Anal. Chim. Acta 2013, 760, 53-59. 28 Lee, P.C.; Miesel, D. Adsorption and surface-enhanced Raman of dyes on silver and gold sols. J. Phys. Chem., 1982, 86, 3391–3395. 29 Jaumot, J.; de Juan, A.; Tauler, R. MCR-ALS GUI 2.0: New features and applications. Chemom. Intell. Lab. Syst. 2015, 15, 1−12. 30 Sun, S.; Brown, A. Simulation of the Resonance Raman Spectra for


Page 9 of 10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


5-Halogenated (F, Cl, and Br) Uracils. J. Phys. Chem. A. 2015, 119, 3961-3971. 31 Schurmann, R.; Bald, I. Decomposition of DNA Nucleobases by Laser Irradiation of Gold Nanoparticles Monitored by SurfaceEnhanced Raman Scattering. J.Phys. Chem.C. 2016, 120, 3001-3009. 32 Brabec, V.; Niki, K. Raman scattering from adenine, uracil and their derivatives adsorbed at a silver electrode. Collect Czechoslov Chem Commun. 1986, 51, 167-174. 33 Kabeláč, M.; Ryjáček, F.; Hobza, P. Already two water molecules change planar H-bonded structures of the adenine … thymine base pair to the stacked ones : a molecular dynamics simulations study. Phys. Chem. Chem. Phys. 2000, 2, 4906 – 4909. 34 Milovanović, B., Petković, M.; Etinski, M. Raman spectra of aqueous uracil stacked dimer: First principle molecular dynamics simulation. Chem. Phys. Lett. 2018, 713, 15–20. 35 Jensen, L. Surface-Enhanced Vibrational Raman Optical Activity: A time dependent Density Functional Theory Approach. J. Phys. Chem. A 2009, 113, 4437-4444.

Alcolea Palafox, M., Rastogi, V. K. Quantum chemical predictions of the vibrational spectra of polyatomic molecules: The uracil molecule and two derivatives. Spectrochim. Acta Part A. 2002, 58, 411-440. 37 Sowers, L.C.; Eritja, R.; Kaplan, B.; Goodman, M.F; Fazakerly, G.V. Equilibrium between a Wobble and Ionized Base Pair Formed between Fluorouracil and Guanine in DNA as Studied by Proton and Fluorine NMR J. Biol.Chem., 1988, 29, 14794-14801. 38 Pergolese, B.; Bonifacio, A.; Bigotto, A. SERS studies of the adsorption of guanine derivatives on gold colloidal nanoparticles. Phys.Chem.Chem.Phys. 2005, 7, 3610-3613. 39 Brown, S. D. Chemical Systems Under Indirect Observation: Latent Properties and Chemometrics. Appl. Spectrosc. 1995, 49, 14A-31A. 40 Olivieri, A.; Nicolaas, M. F.; Ferré, J.; Boqué, R.; Kalivas, J. H.; Howard, M. Uncertainty estimation and figures of merit for multivariate calibration. Pure Appl. Chem. 2006, 78, 633-661. 36




Page 10 of 10

10

On the Cooperativity Effect in Watson and Crick and Wobble Pairs for

Recommend Documents