A perspective on the ultrafast photochemistry of solution-phase sunscreen molecules

Sunscreens are one of the most common ways of providing on-demand additional photoprotection to the skin. Ultrafast transient absorption spectroscopy has recently proven to be an invaluable tool in understanding how the components of commercial sunscreen products display efficient photoprotection. Important examples of how this technique has unravelled the photodynamics of common components are given in this Perspective, and some of the remaining unanswered questions are discussed

Excited-state dynamics of a two-photon-activatable ruthenium prodrug

We present a new approach to investigate how the photodynamics of an octahedral ruthenium(II) complex activated through two-photon absorption (TPA) differ from the equivalent complex activated through one-photon absorption (OPA). We photoactivated a RuII polypyridyl complex containing bioactive monodentate ligands in the photodynamic therapy window (620–1000 nm) by using TPA and used transient UV/Vis absorption spectroscopy to elucidate its reaction pathways. Density functional calculations allowed us to identify the nature of the initially populated states and kinetic analysis recovers a photoactivation lifetime of approximately 100 ps. The dynamics displayed following TPA or OPA are identical, showing that TPA prodrug design may use knowledge gathered from the more numerous and easily conducted OPA studies

Bridging the gap between the gas and solution phase : solvent specific photochemistry in 4-tert-butylcatechol

Eumelanin is a naturally synthesized ultraviolet light absorbing biomolecule, possessing both photoprotective and phototoxic properties. We infer insight into these properties of eumelanin using a bottom-up approach, by investigating a subunit analogue, 4-tert-butylcatechol. Utilizing a combination of femtosecond transient electronic absorption spectroscopy and time-re-solved velocity map ion imaging, our results suggest an environmental-dependent relaxation pathway, following irradiation at 267 nm to populate the S1 (1ππ*) state. Gas-phase and non-polar solution-phase measurements reveal that the S1 state decays through coupling onto the S2 (1πσ*) state that is dissociative along the non-intramolecular hydrogen bonded ‘free’ O–H bond. This process is mediated by tunneling beneath an S1/S2 conical intersection and occurs in 4.9 ± 0.6 ps in the gas-phase and 27 ± 7 ps in the non-polar cyclohexane solution. Comparative studies on the deuterated isotopologue of 4-tert-butylcatechol in both the gas- and solution-phase (cyclohexane) reveals an average kinetic isotope effect of ~19 and ~7, respectively, supportive of O–H dissociation mediated by a quantum tunneling mechanism. In contrast, in the polar acetonitrile, the S1 state decays on a much longer timescale of 1.7 ± 0.1 ns. We propose that the S1 decay is now multicomponent, likely driven by internal conversion, intersystem crossing and fluorescence, as well as O–H dissociation. The attribution of conformer driven excited state dynamics to explain how the S1 state decays in the gas- and non-polar solution-phase versus the polar solution-phase, elegantly demonstrates the influence the environment has on the ensuing excited state dynamics

Combatting AMR : photoactivatable ruthenium(ii)-isoniazid complex exhibits rapid selective antimycobacterial activity

The novel photoactive ruthenium(II) complex cis-[Ru(bpy)2(INH)2][PF6]2 (1·2PF6, INH = isoniazid) was designed to incorporate the anti-tuberculosis drug, isoniazid, that could be released from the Ru(II) cage by photoactivation with visible light. In aqueous solution, 1 rapidly released two equivalents of isoniazid and formed the photoproduct cis-[Ru(bpy)2(H2O)2]2+ upon irradiation with 465 nm blue light. We screened for activity against bacteria containing the three major classes of cell envelope: Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, and Mycobacterium smegmatis in vitro using blue and multi-colored LED multi-well arrays. Complex 1 is inactive in the dark, but when photoactivated is 5.5× more potent towards M. smegmatis compared to the clinical drug isoniazid alone. Complementary pump-probe spectroscopy measurements along with density functional theory calculations reveal that the mono-aqua product is formed in <500 ps, likely facilitated by a 3MC state. Importantly, complex 1 is highly selective in killing mycobacteria versus normal human cells, towards which it is relatively non-toxic. This work suggests that photoactivatable prodrugs such as 1 are potentially powerful new agents in combatting the global problem of antibiotic resistance

Probing the ultrafast energy dissipation mechanism of the sunscreen oxybenzone after UVA irradiation

Oxybenzone is a common constituent of many commercially available sunscreens providing photoprotection from ultraviolet light incident on the skin. Femtosecond transient electronic and vibrational absorption spectroscopies have been used to investigate the non-radiative relaxation pathways of oxybenzone in cyclohexane and methanol after excitation in the UVA region. The present data suggest that the photoprotective properties of oxybenzone can be understood in terms of an initial ultrafast excited state enol -> keto tautomerization, followed by efficient internal conversion and subsequent vibrational relaxation to the ground state (enol) tautomer

Unusual Polymorphisms in Human Immunodeficiency Virus Type 1 Associated with Nonprogressive Infection

Factors accounting for long-term nonprogression may include infection with an attenuated strain of human immunodeficiency virus type 1 (HIV-1), genetic polymorphisms in the host, and virus-specific immune responses. In this study, we examined eight individuals with nonprogressing or slowly progressing HIV-1 infection, none of whom were homozygous for host-specific polymorphisms (CCR5-Δ32, CCR2-64I, and SDF-1-3\u27A) which have been associated with slower disease progression. HIV-1 was recovered from seven of the eight, and recovered virus was used for sequencing the full-length HIV-1 genome; full-length HIV-1 genome sequences from the eighth were determined following amplification of viral sequences directly from peripheral blood mononuclear cells (PBMC). Longitudinal studies of one individual with HIV-1 that consistently exhibited a slow/low growth phenotype revealed a single amino acid deletion in a conserved region of the gp41 transmembrane protein that was not seen in any of 131 envelope sequences in the Los Alamos HIV-1 sequence database. Genetic analysis also revealed that five of the eight individuals harbored HIV-1 with unusual 1- or 2-amino-acid deletions in the Gag sequence compared to subgroup B Gag consensus sequences. These deletions in Gag have either never been observed previously or are extremely rare in the database. Three individuals had deletions in Nef, and one had a 4-amino-acid insertion in Vpu. The unusual polymorphisms in Gag, Env, and Nef described here were also found in stored PBMC samples taken 3 to 11 years prior to, or in one case 4 years subsequent to, the time of sampling for the original sequencing. In all, seven of the eight individuals exhibited one or more unusual polymorphisms; a total of 13 unusual polymorphisms were documented in these seven individuals. These polymorphisms may have been present from the time of initial infection or may have appeared in response to immune surveillance or other selective pressures. Our results indicate that unusual, difficult-to-revert polymorphisms in HIV-1 can be found associated with slow progression or nonprogression in a majority of such cases

Social Transfer of Pathogenic Fungus Promotes Active Immunisation in Ant Colonies

Social contact with fungus-exposed ants leads to pathogen transfer to healthy nest-mates, causing low-level infections. These micro-infections promote pathogen-specific immune gene expression and protective immunization of nest-mates

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Developmental delay in early childhood is associated with visual-constructive skills at school age in a Brazilian cohort

Abstract We investigated differences in IQ and visual-constructive skills in school-age children evaluated as developmentally delayed or typically developed in early childhood. Sixty-four participants from a Brazilian cohort were evaluated in IQ (Wechsler Abbreviated Scale of Intelligence) and tasks of visual-spatial memory and visual-constructive skills through the Benton Visual Retention Test (BVRT) at school age. Neuropsychomotor development at 4 years of age was measured by Denver II. Developmentally delayed children showed lower IQs, lower scores, and more errors in copy and memory BVRT tasks when compared to typically developed children. Delay in neuropsychomotor development in early childhood may affect the subsequent cognitive development of children