Indoor secondary organic aerosols: Towards an improved representation of their formation and composition in models.

The formation of secondary organic aerosol (SOA) indoors is one of the many consequences of the rich and complex chemistry that occurs therein. Given particulate matter has well documented health effects, we need to understand the mechanism for SOA formation indoors and its resulting composition. This study evaluates some uncertainties that exist in quantifying gas-to-particle partitioning of SOA-forming compounds using an indoor detailed chemical model. In particular, we investigate the impacts of using different methods to estimate compound vapour pressures as well as simulating the formation of highly oxygenated organic molecules (HOM) via auto-oxidation on SOA formation indoors. Estimation of vapour pressures for 136 α-pinene oxidation species by six investigated methods led to standard deviations of 28-216%. Inclusion of HOM formation improved model performance across three of the six assessed vapour pressure estimation methods when comparing against experimental data, particularly when the NO2 concentration was relatively high. We also explored the predicted SOA composition using two product classification methods, the first assuming the molecule is dominated by one functionality according to its name, and the second accounting for the fractional weighting of each functional group within a molecule. The SOA composition was dominated by the HOM species when the NO2-to-α-terpineol ratio was high for both product classification methods, as these conditions promoted formation of the nitrate radical and hence formation of HOM monomers. As the NO2-to-α-terpineol ratio decreased, peroxides and acids dominated the simple classification, whereas for the fractional classification, carbonyl and alcohol groups became more important.

Weight gain in early pregnancy and risk of gestational diabetes mellitus among Latinas.

AIM: To evaluate the association between gestational weight gain (GWG) in early pregnancy and incidence of abnormal glucose tolerance (AGT) and gestational diabetes mellitus (GDM) among Latinas. METHODS: We conducted a retrospective cohort study of 2039 Latinas using pooled data from two medical centres in Massachusetts. Gestational weights were abstracted from medical records and GWG was categorized as low, appropriate and excessive according to 2009 Institute of Medicine Guidelines. Diagnosis of AGT and GDM was confirmed by study obstetricians. RESULTS: A total of 143 women (7.0%) were diagnosed with GDM and 354 (17.4%) with AGT. After adjusting for age and study site, women with low GWG up to the time of GDM screen had a lower odds of GDM (OR: 0.51, 95% CI: 0.29-0.92). Among overweight women, women with excessive first-trimester GWG had 2-fold higher odds of AGT (OR: 1.96, 95% CI: 1.17-3.30) and GDM (OR: 2.07, 95% CI: 1.04-4.12) compared to those with appropriate GWG; however, these findings were not significant among normal weight or obese women. CONCLUSION: Among Latinas, low GWG up to the time of GDM screen was associated with lower odds of AGT and GDM, while excessive GWG among overweight women was associated with higher odds. Findings highlight need for interventions in early pregnancy to help women meet GWG guidelines and to moderate GWG among overweight Latinas.

Outcome-based ventilation: A framework for assessing performance, health, and energy impacts to inform office building ventilation decisions.

This article presents an outcome-based ventilation (OBV) framework, which combines competing ventilation impacts into a monetized loss function ($/occ/h) used to inform ventilation rate decisions. The OBV framework, developed for U.S. offices, considers six outcomes of increasing ventilation: profitable outcomes realized from improvements in occupant work performance and sick leave absenteeism; health outcomes from occupant exposure to outdoor fine particles and ozone; and energy outcomes from electricity and natural gas usage. We used the literature to set low, medium, and high reference values for OBV loss function parameters, and evaluated the framework and outcome-based ventilation rates using a simulated U.S. office stock dataset and a case study in New York City. With parameters for all outcomes set at medium values derived from literature-based central estimates, higher ventilation rates' profitable benefits dominated negative health and energy impacts, and the OBV framework suggested ventilation should be ≥45 L/s/occ, much higher than the baseline ~8.5 L/s/occ rate prescribed by ASHRAE 62.1. Only when combining very low parameter estimates for profitable impacts with very high ones for health and energy impacts were all outcomes on the same order. Even then, however, outcome-based ventilation rates were often twice the baseline rate or more.

Reactive indoor air chemistry and health-A workshop summary.

The chemical composition of indoor air changes due to the reactive nature of the indoor environment. Historically, only the stable parent compounds were investigated due to their ease of measurement by conventional methods. Today, however, scientists can better characterize oxidation products (gas and particulate-phase) formed by indoor chemistry. An understanding of occupant exposure can be developed through the investigation of indoor oxidants, the use of derivatization techniques, atmospheric pressure detection, the development of real-time technologies, and improved complex modeling techniques. Moreover, the connection between exposure and health effects is now receiving more attention from the research community. Nevertheless, a need still exists for improved understanding of the possible link between indoor air chemistry and observed acute or chronic health effects and long-term effects such as work-related asthma.

Airborne particles in indoor environment of homes, schools, offices and aged care facilities: The main routes of exposure.

It has been shown that the exposure to airborne particulate matter is one of the most significant environmental risks people face. Since indoor environment is where people spend the majority of time, in order to protect against this risk, the origin of the particles needs to be understood: do they come from indoor, outdoor sources or both? Further, this question needs to be answered separately for each of the PM mass/number size fractions, as they originate from different sources. Numerous studies have been conducted for specific indoor environments or under specific setting. Here our aim was to go beyond the specifics of individual studies, and to explore, based on pooled data from the literature, whether there are generalizable trends in routes of exposure at homes, schools and day cares, offices and aged care facilities. To do this, we quantified the overall 24h and occupancy weighted means of PM10, PM2.5 and PN - particle number concentration. Based on this, we developed a summary of the indoor versus outdoor origin of indoor particles and compared the means to the WHO guidelines (for PM10 and PM2.5) and to the typical levels reported for urban environments (PN). We showed that the main origins of particle metrics differ from one type of indoor environment to another. For homes, outdoor air is the main origin of PM10 and PM2.5 but PN originate from indoor sources; for schools and day cares, outdoor air is the source of PN while PM10 and PM2.5 have indoor sources; and for offices, outdoor air is the source of all three particle size fractions. While each individual building is different, leading to differences in exposure and ideally necessitating its own assessment (which is very rarely done), our findings point to the existence of generalizable trends for the main types of indoor environments where people spend time, and therefore to the type of prevention measures which need to be considered in general for these environments.

Real-time transformation of outdoor aerosol components upon transport indoors measured with aerosol mass spectrometry.

Outdoor aerosols are transported indoors, where their component concentrations depend on aerosol size, physiochemical properties, indoor sources and losses, and cross-environment gradients of temperature and relative humidity. We explored these dependencies by measuring real-time outdoor and indoor non-refractory, submicron (PM1 ) aerosol component mass concentrations in a mixed-use laboratory space with an Aerodyne mini-aerosol mass spectrometer (AMS) and black carbon (BC) with an aethalometer. The median indoor/outdoor (I/O) ratios were 0.60 for sulfate, 0.25 for nitrate, 0.52 for ammonium, 0.73 for organics, and 0.61 for BC. Positive matrix factorization (PMF) on organic aerosol data identified hydrocarbon-like (HOA), cooking (COA), and oxygenated (OOA) factors. By assuming sulfate was nonvolatile, lost only by mechanical processes, and without indoor sources, the transformations of other components i due to partitioning changes or indoor sources were parameterized by normalizing their I/O ratios by sulfate's I/O ratio, that is, (I/O)i/SO4 . Component-specific behavior was quantified by regressions of (I/O)i/SO4 to outdoor-to-indoor temperature differences. Nitrate and HOA strongly and OOA weakly showed losses with increasing temperatures indoors vs. outdoors, and HOA likely had an indoor source. To our knowledge, this is the first reported deployment of an AMS to analyze real-time indoor aerosol composition and outdoor-to-indoor transformation.

Secondary organic aerosol formation initiated by α-terpineol ozonolysis in indoor air.

Secondary organic aerosol (SOA) owing to reactive organic gas (ROG) ozonolysis can be an important indoor particle source. However, SOA formation owing to ozonolysis of α-terpineol, which is emitted by consumer product usage and reacts strongly with ozone, has not been systematically quantified. Therefore, we conducted 21 experiments to investigate the SOA formation initiated by α-terpineol ozonolysis for high (0.84 h-1 ), moderate (0.61 h-1 ), and low (0.36 h-1 ) air exchange rates (AER), which is the frequency with which indoor is replaced by outdoor air. α-Terpineol concentrations of 6.39 to 226 ppb were combined with high ozone (~25 ppm) to ensure rapid and complete ozonolysis. No reactants were replenished, so SOA peaked quickly and then decreased due to AER and surface losses, and peak SOA ranged from 2.03 to 281 µg/m3 at unit density. SOA mass formation was parameterized with the aerosol mass fraction (AMF), a.k.a. the SOA yield, and AMFs ranged from 0.056 to 0.24. The AMFs strongly and positively correlated with reacted α-terpineol, whereas they weakly and negatively correlated with higher AERs. One-product, two-product, and volatility basis set (VBS) models were fit to the AMF data. Predictive modeling demonstrated that α-terpineol ozonolysis could meaningfully form SOA in indoor air.

Perceptions in the U.S. building industry of the benefits and costs of improving indoor air quality.

How building stakeholders (e.g. owners, tenants, operators, and designers) understand impacts of Indoor Air Quality (IAQ) and associated energy costs is unknown. We surveyed 112 stakeholders across the United States to ascertain their perceptions of their current IAQ and estimates of benefits and costs of, as well as willingness to pay for, IAQ improvements. Respondents' perceived IAQ scores correlated with the use of high-efficiency filters but not with any other IAQ-improving technologies. We elicited their estimates of the impacts of a ventilation-filtration upgrade (VFU), that is, doubling the ventilation rate from 20 to 40 cfm/person (9.5 to 19 l/s/person) and upgrading from a minimum efficiency reporting value 6 to 11 filter, and compared responses to estimates derived from IAQ literature and energy modeling. Minorities of respondents thought the VFU would positively impact productivity (45%), absenteeism (23%), or health (39%). Respondents' annual VFU cost estimates (mean = $257, s.d. = $496, median = $75 per person) were much higher than ours (always <$32 per person), and the only yearly cost a plurality of respondents said they would pay for the VFU was $15 per person. Respondents holding green building credentials were not more likely to affirm the IAQ benefits of the VFU and were less likely to be willing to pay for it.

Do time-averaged, whole-building, effective volatile organic compound (VOC) emissions depend on the air exchange rate? A statistical analysis of trends for 46 VOCs in U.S. offices.

We used existing data to develop distributions of time-averaged air exchange rates (AER), whole-building 'effective' emission rates of volatile organic compounds (VOC), and other variables for use in Monte Carlo analyses of U.S. offices. With these, we explored whether long-term VOC emission rates were related to the AER over the sector, as has been observed in the short term for some VOCs in single buildings. We fit and compared two statistical models to the data. In the independent emissions model (IEM), emissions were unaffected by other variables, while in the dependent emissions model (DEM), emissions responded to the AER via coupling through a conceptual boundary layer between the air and a lumped emission source. For 20 of 46 VOCs, the DEM was preferable to the IEM and emission rates, though variable, were higher in buildings with higher AERs. Most oxygenated VOCs and some alkanes were well fit by the DEM, while nearly all aromatics and halocarbons were independent. Trends by vapor pressure suggested multiple mechanisms could be involved. The factors of temperature, relative humidity, and building age were almost never associated with effective emission rates. Our findings suggest that effective emissions in real commercial buildings will be difficult to predict from deterministic experiments or models.

Secondary organic aerosol in residences: predicting its fraction of fine particle mass and determinants of formation strength.

UNLABELLED: Indoor secondary organic aerosol (SOA) formation may contribute to particle concentrations within residences, but little systematic work has investigated its magnitude or the determinants of its formation. This work uses a time-averaged modeling approach to predict the indoor SOA mass formed in residences due to the oxidation of 66 reactive organic compounds by ozone or the hydroxyl radical, parameterizing SOA formation with the aerosol mass fraction. Other organic and inorganic aerosols owing to outdoor and indoor sources were also predicted. Model inputs were represented as distributions within a Monte Carlo analysis, so that result distributions and sensitivity of results to inputs could be quantified, using a dataset developed from the study of Relationships between Indoor, Outdoor and Personal Air and other sources. SOA comprised a large amount of indoor organic and total fine particles for a subset of the results (e.g., >47% of indoor organic and >30% of fine aerosol for 10% of the modeled cases), but was often a small fraction. The sensitivity analysis revealed that SOA formation is driven by high terpene emission rates (particularly by d-limonene) and outdoor ozone, along with low air exchange and ozone and particle deposition rates. PRACTICAL IMPLICATIONS: This study predicts that indoor SOA formation can be a substantial fraction of indoor aerosols in residences, for certain combinations of building and reactant parameters. The model herein can predict SOA for risk analyses or be used to design experiments to study indoor SOA formation. The terpene, d-limonene, contributes by far the most to formation, and eliminating this particular compound indoors would be impactful on indoor aerosol concentrations.

Indoor aerosols: from personal exposure to risk assessment.

Motivated by growing considerations of the scale, severity, and risks associated with human exposure to indoor particulate matter, this work reviewed existing literature to: (i) identify state-of-the-art experimental techniques used for personal exposure assessment; (ii) compare exposure levels reported for domestic/school settings in different countries (excluding exposure to environmental tobacco smoke and particulate matter from biomass cooking in developing countries); (iii) assess the contribution of outdoor background vs indoor sources to personal exposure; and (iv) examine scientific understanding of the risks posed by personal exposure to indoor aerosols. Limited studies assessing integrated daily residential exposure to just one particle size fraction, ultrafine particles, show that the contribution of indoor sources ranged from 19% to 76%. This indicates a strong dependence on resident activities, source events and site specificity, and highlights the importance of indoor sources for total personal exposure. Further, it was assessed that 10-30% of the total burden of disease from particulate matter exposure was due to indoor-generated particles, signifying that indoor environments are likely to be a dominant environmental factor affecting human health. However, due to challenges associated with conducting epidemiological assessments, the role of indoor-generated particles has not been fully acknowledged, and improved exposure/risk assessment methods are still needed, together with a serious focus on exposure control.

Randomized controlled trial of behavioral treatment for comorbid obesity and depression in women: the Be Active Trial.

OBJECTIVE: Depression is associated with increased risk for obesity and worse weight loss treatment outcomes. The purpose of the present study was to test the hypothesis that delivering evidence-based behavior therapy for depression before a lifestyle weight loss intervention improves both weight loss and depression. DESIGN: In a randomized controlled trial, obese women with major depressive disorder (N=161, mean age=45.9 (s.d.: 10.8) years) were randomized to brief behavior therapy for depression treatment followed by a lifestyle intervention (BA) or a lifestyle intervention only (LI). Follow-up occurred at 6 and 12 months. Main outcome measures included weight loss and depression symptoms. RESULTS: Intention-to-treat analyses revealed both conditions lost significant weight, but no differences between conditions in weight change at 6 months (BA=-3.0%, s.e.=-0.65%; LI=-3.7%, s.e.=0.63%; P=0.48) or 12 months (BA=-2.6%, s.e.=0.77%; LI=-3.1%, s.e.=0.74%; P=0.72). However, the BA condition evidenced significantly greater improvement in Beck Depression Inventory-II scores relative to the LI condition at both 6 months (BA mean change=-12.5, s.d.=0.85; LI mean change=-9.2, s.d.=0.80, P=0.005) and 12 months (BA mean change=-12.6, s.d.=0.97; LI mean change=-9.9, s.d.=0.93; P=0.045). Participants who experienced depression remission by 6 months (61.2%) lost greater weight (mean=-4.31%; s.e.=0.052) than those who did not (39.7%; mean=-2.47%, s.e.=0.53; P=.001). CONCLUSION: Adding behavior therapy to a lifestyle intervention results in greater depression remission but does not improve weight loss within 1 year. Improvement in depression is associated with greater weight loss.

Predicting secondary organic aerosol formation from terpenoid ozonolysis with varying yields in indoor environments.

UNLABELLED: The ozonolysis of terpenoids generates secondary organic aerosol (SOA) indoors. Models of varying complexity have been used to predict indoor SOA formation, and many models use the SOA yield, which is the ratio of the mass of produced SOA and the mass of consumed reactive organic gas. For indoor simulations, the SOA yield has been assumed as a constant, even though it depends on the concentration of organic particles in the air, including any formed SOA. We developed two indoor SOA formation models for single terpenoid ozonolysis, with yields that vary with the organic particle concentration. The models have their own strengths and were in agreement with published experiments for d-limonene ozonolysis. Monte Carlo analyses were performed, which simulated different residential and office environments to estimate ranges of SOA concentrations and yields for d-limonene and α-pinene ozonolysis occurring indoors. Results indicate that yields are highly variable indoors and are most influenced by background organic particles for steady-state formation and indoor ozone concentration for transient peak formation. Additionally, a review of ozonolysis yields for indoor-relevant terpenoids in the literature revealed much uncertainty in their values at low concentrations typical of indoors. PRACTICAL IMPLICATIONS: The results in this study suggest important factors that govern indoor secondary organic aerosol (SOA) formation and yields, in typical residential and office spaces. This knowledge informs the development and comparison of control strategies to reduce indoor-generated SOA. The ranges of SOA concentrations predicted indoors allow the quantification of the effects of sorptive interactions of semi-volatile organic compounds or reactive oxygen species with SOA, filter loading owing to SOA formation, and impacts of SOA on health, if links are established.

An evaluation of the skin stripping of wound dressing adhesives.

OBJECTIVE: This study looks at six different modern wound dressings to investigate how likely they are to cause skin stripping and impairment of the skin's barrier function. METHOD: Healthy volunteers had each dressing applied, removed and reapplied to the skin on their back over the study period of 15 days. Skin barrier function was investigated using the amount of transepidermal water loss (TEWL) and then related to the amount of skin stripping, investigated by measuring stained skin removal, the thickness of the stratum corneum after treatment, and the amount of skin attached to the removed dressings. General signs of trauma, such as skin dryness and erythema, were investigated by subjective and objective parameters. RESULTS: TEWL values measured on the untreated test area, as well as after application of Urgotul Trio, remained relatively unchanged and Mepilex Border decreased slightly (?1g/m2/h), while all other dressings displayed an increased in TEWL: Allevyn Adhesive (5g/m2/h), Versiva XC (14g/m2/h), Comfeel Plus (22g/m2/h) and Biatain (28g/m2/h). By the end of the study, only the untreated area (mean 43% dye remaining), Mepilex Border (76%) and Urgotul Trio (34%) areas had visible dye remaining. It is interesting to note that the untreated site had a colour change, suggesting loss of stratum corneum, due to the shedding of skin cells from the surface. The increase in total skin colour for Comfeel Plus and Biatain after day 8 might be assigned to an increased redness due to erythema. All the dressings showed evidence of stratum corneum attached to the adhesive, except Mepilex Border, which appeared to be free of any attached stratum corneum. CONCLUSION: Overall the best performance in terms of skin protection and failure to cause skin trauma was found to be for Mepilex Border. CONFLICT OF INTEREST: This project was funded by a grant from Mölnlycke Healthcare Ltd.

The effect of an ion generator on indoor air quality in a residential room.

UNLABELLED: Ion generators charge particles with a corona prior to their removal on collector plates or indoor surfaces and also emit ozone, which can react with terpenes to yield secondary organic aerosol, carbonyls, carboxylic acids, and free radicals. This study characterized the indoor air quality implications of operating an ion generator in a 27 m(3) residential room, with four different test room configurations. Two room configurations had carpet overlaying the original flooring of stained/sealed concrete, and for one configuration with and without carpet, a plug-in air freshener was used as a terpene source. Measurements included airborne sampling of particulate matter (0.015-20 µm), terpenes and C(1) -C(4) and C(6) -C(10) aldehydes, ozone concentrations, and air exchange rates. When the heating, ventilating, and air-conditioning system was not operating (room air exchange rate = ∼0.5/h), the use of the ion generator in the presence of the air freshener led to a net increase in ultrafine particles (<0.1 µm). Also, increased concentrations of ozone were observed regardless of air freshener presence, as well as increases in formaldehyde and nonanal, albeit within measurement uncertainty in some cases. Thus, it may be prudent to limit ion generator use indoors until evidence of safety can be ascertained. PRACTICAL IMPLICATIONS: Portable ion generators are intended to clean the air of particles, but they may emit ozone as a byproduct of their operation, which has the potential to degrade indoor air quality. This study showed that under certain conditions in a residential room, the use of a portable ion generator can increase concentrations of ozone and, to a lesser degree, potentially aldehydes. Also, if operated in the presence of a plug-in air freshener that emits terpenes, its use can increase concentrations of secondary organic aerosol in the ultrafine size range.

Clinical and scientific data on a silver-containing soft-silicone foam dressing: an overview.

Antimicrobial agents, including silver, are often used either alone or with antibiotics to treat or prevent infection. This paper reviews the existing in vitro and in vivo evidence on one such antimicrobial commonly used on wounds.

Particle loading rates for HVAC filters, heat exchangers, and ducts.

UNLABELLED: The rate at which airborne particulate matter deposits onto heating, ventilation, and air-conditioning (HVAC) components is important from both indoor air quality (IAQ) and energy perspectives. This modeling study predicts size-resolved particle mass loading rates for residential and commercial filters, heat exchangers (i.e. coils), and supply and return ducts. A parametric analysis evaluated the impact of different outdoor particle distributions, indoor emission sources, HVAC airflows, filtration efficiencies, coils, and duct system complexities. The median predicted residential and commercial loading rates were 2.97 and 130 g/m(2) month for the filter loading rates, 0.756 and 4.35 g/m(2) month for the coil loading rates, 0.0051 and 1.00 g/month for the supply duct loading rates, and 0.262 g/month for the commercial return duct loading rates. Loading rates are more dependent on outdoor particle distributions, indoor sources, HVAC operation strategy, and filtration than other considered parameters. The results presented herein, once validated, can be used to estimate filter changing and coil cleaning schedules, energy implications of filter and coil loading, and IAQ impacts associated with deposited particles. PRACTICAL IMPLICATIONS: The results in this paper suggest important factors that lead to particle deposition on HVAC components in residential and commercial buildings. This knowledge informs the development and comparison of control strategies to limit particle deposition. The predicted mass loading rates allow for the assessment of pressure drop and indoor air quality consequences that result from particle mass loading onto HVAC system components.

Precision of intracellular calcium spike timing in primary rat hepatocytes.

Extracellular stimuli are often encoded in the frequency, amplitude and duration of spikes in the intracellular concentration of calcium ([Ca2+]i). However, the timing of individual [Ca2+]i-spikes in relation to the dynamics of an extracellular stimulus is still an open question. To address this question, we use a systems biology approach combining experimental and theoretical methods. Using computer simulations, we predict that more naturalistic pulsed stimuli generate precisely-timed [Ca2+]i-spikes in contrast to the application of constant stimuli of the same dose. These computational results are confirmed experimentally in single primary rat hepatocytes upon alpha1-adrenergic stimulation. Hormonal signalling in analogy to neuronal signalling thus has the potential to make use of temporal coding on the level of single cells. The [Ca2+]i-signalling cascade provides a first example for increasing the information capacity of an intracellular regulatory signal beyond the known coding mechanisms of amplitude (AM) and frequency modulation (FM).

Sequence-specific DNA cleavage by dipeptides disubstituted with chlorambucil and 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid.

Two dipeptides, each containing a lysyl residue, were disubstituted with chlorambucil (CLB) and 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA): DMQ-MA-Lys(CLB)-Gly-NH2 (DM-KCG) and DMQ-MA-beta-Ala-Lys(CLB)-NH2 (DM-BKC). These peptide-drug conjugates were designed to investigate sequence-specificity of DNA cleavage directed by the proximity effect of the DNA cleavage chromophore (DMQ-MA) situated close to the alkylating agent (CLB) inside a dipeptide moiety. Agarose electrophoresis studies showed that DM-KCG and DM-BKC possess significant DNA nicking activity toward supercoiled DNA whereas CLB and its dipeptide conjugate Boc-Lys(CLB)-Gly-NH2 display little DNA nicking activity. ESR studies of DMQ-MA and DM-KCG both showed five hyperfine signals centered at g = 2.0052 and are assigned to four radical forms at equilibrium, which may give rise to a semiquinone radical responsible for DNA cleavage. Thermal cleavage studies at 90 degrees C on a 265-mer test DNA fragment showed that besides alkylation and cleavage at G residues, reactions with DM-KCG and DM-BKC show a preference for A residues with the sequence pattern: 5'-G-(A)n-Pur-3' > 5'-Pyr-(A)n-Pyr-3' (where n = 2-4). By contrast, DNA alkylation and cleavage by CLB occurs at most G and A residues with less sequence selectivity than seen with DM-KCG and DM-BKC. Thermal cleavage studies using N7-deazaG and N7-deazaA-substituted DNA showed that strong alkylation and cleavage at A residues by DM-KCG and DM-BKC is usually flanked on the 3' side by a G residue whereas strong cleavage at G residues is flanked by at least one purine residue on either the 5' or 3' side. At 65 degrees C, it is notable that the preferred DNA cleavage by DM-KCG and DM-BKC at A residues is significantly more marked than for G residues in the 265-mer DNA; the strongest sites of A-specific reaction occur within the sequences 5'-Pyr-(A)n-Pyr-3'; 5'-Pur-(A)n-G-3' and 5'-Pyr-(A)n-G-3'. In pG4 DNA, cleavage by DM-KCG and DM-BKC is much greater than that by CLB at room temperature and at 65 degrees C. It was also observed that DM-KCG and DM-BKC cleaved at certain pyrimidine residues: C40, T66, C32, T34, and C36. These cleavages were also sequence selective since the susceptible pyrimidine residues were flanked by two purine residues on both the 5' and 3' sides or by a guanine residue on the 5' side. These findings strongly support the proposal that once the drug molecule is positioned so as to permit alkylation by the CLB moiety, the DMQ-MA moiety is held close to the alkylation site, resulting in markedly enhanced sequence-specific cleavage.